Schulz Exhibit 4

8/7/2019 Schulz Exhibit 4

1/61

, ,

CONT INUAT ION PAGE Principallnvesligator/Program Director O lso n, S te ph en C(Lasl, lirs~ middle):FY2003 33.10% 31.10%FY2004 33.10% 31.10"~FY2005 33.10% 31.10%GRADUATE I PROFESS IONAL TRA lt JlNG S TUD EN T S F ri ng e R at es :F ri ng e v a ri es by in div id ua l b ase d o n p erc en t of tim e ap po in ted an d th e n um ber of c re d it s .

..... P ER SONN EL J lI ST IF IC A TI ON S " ...O l son , P r inc i p


2/61

L.._:-.:;;:r~-~ ...;-:. MEDICAL SCHOOL ADMINTSTRATION - RESEARCH PROGRAMS

C685 MAYO BUILDING

Ptincipel lnvestiqsior; Stephen Olson, M.D.(Typed Name) ~dJ l~Ignature

Department: PsychiatryCo-lnvestigator(s): Charles Schulz, MD., John Vuchetich, M.D.Industria! Sponsor: AstraZenecaProject Title: Efficacy and Tolerability of Olanzapine, Quetlaplne and Risperidone in the Treatment ofRrst EpisodePsychosis: A Randomized Double Bl ind 52.;.WeekComparisonSummary of Peer Revlew:1. Faculty Effort Certification:

a) Percent of effort dedicated to this projectb) Percent of salary (Sma/leror total salary or N/H cap)c) Does a = b7d) This percent effort is appropriate for this project

2. There is sufficient space and time to conduct this research.3. This research is consistent with Division and Department goals.

%%

NoNoNoNo

4. Conflict of Interest (COl) regarding PI's Business and Financial issues: (see AREPA Definitions in EGMS)a) PRF/BA23 form is completed and signed by PI and department heads. If~ Nob) AREPA Form15# has ben approved within the lasl12 months. ~. No

wE ~d) This project involves a "GIFT value\! at $1,000 or more.If Yes, the disclosure explanation is attached.

Name and Signature of Peer Review Panei Designee or Division Director____ ,/7) ;'7-'~r /'-S/?-'1A '_.Cb==

Chairperson or Vice-Chairperson Approval date

This project has been reviewed under the Department of Psychiatry Peer Review process and isrecommended as being appropriate for submlsalon. The submitting faculty member has provided assurancethat any po e tlal conn! t of in erest has been disclosed.

TH1S PEER REVIEW FORM CAN BE USED FOR ANY AGENCY GRANT APPLICATIONGrants\2000HowTos.doc Questions? Ca1l6253343 12/8 /00

UM SPA 0228


3/61

Exhibit ASTUDY BUDGET, PAYMENT SCHEDULE AND PROCEDURES

PROTOCOL NO: S077IL10114 INSTITUTION: University of MinnesotaPRINCIPAL INVESTIGATOR: Stephen Olson, M.D.PATIENT ENROLLMENT CLOSING DATE: August 2003OAT A COMPLETION DATE: September 2004MINIMUM ENROLLMENT: 20 SubjectsMAXIMUM ENROLLMENT: 30 Subjects

BREAKDOWN OF PA YMENTS

L INITIAL PAYMENT $16,362Upon receipt and approval of all regulatory documents and this signed Clinical Study Agreement, AstraZeneca shallforward a payment of $16,}62 to the representative noted below. This Initial Payment is a refundable, advancepayment for the first patient enrolled and will be deducted from future Per Subject Payments .. If Institution does notenroll at least I Subject into the Study within 8 weeks of the date of its receipt of the Study Drug, this Agreementmay be immediately terminated by AstraZeneca, and Institution shall refund to AstraZeneca the $16,}62 InitialPayment

UM SPA 0446


4/61

A2:PH100l (01((j{J~

C LIN IC AL S TU DY A GR EEM El'l '1T h is C L IN IC AL S T U DY A GR EEM EN T ("A greem enC '), d a ted as o f th e la s t d a te o f th e s ig n a tu re s b e lo w .

is b y an d am ong A stre .Z e n e ca P h a rm ace u tic a ls L P . a D elaw are lim ite d p a r tn e rsh ip w ith o f fic e s a t 1800 C o nc o rdP ik e . W ilm ing to n . D E 19R 50-5438 C 'A stra 'Z en ec a"), an d The R ege n ts o f th e U n iv e rs ity o f M inn eso ta , aM i nn eso ta c orp or atio n ("I ns titu tio n:-). w ith a facil i ty at 200 O ak S tre e t . S E , M inn e ap o lis , M N 55455 w ith S te ph e nOlson, M .D . a s ("P rin c ip a l In v e s tig a to r"). . ...

W H E R E A S . Astra'Zencca w i s h e s to c ondu c t a m ulti-c en te r c l in ic a l s tu dy o f S eroqu e lt> ' ("S tu dy D rug ");an d

W H ER EA S. In s ti tu t io n h as a pp ro p ria te facil i t ies an d p e rso nn e l. a n d P r in c ip a l In v es tig a to r h a s th equ alif ic a tio n , tra in in g . k n ow led ge a nd exp er ie n ce n ece ss a ry to con du ct su ch a c lin ic a l s tu dy .

N OW . T HER EFO RE , in c on s id e ra tio n o f th e fo reg o in g p rem ise s an d fo r v a lu ab le co n sid e ra tio n , th e re ce ip tan d su f f ic ie n c y o f w hich a re h ereby a ck now le dg e d , th e p a r tie s , in ten din g to b e leg a lly h ou nd . a g ree a s fo llo ws:

1. S co p e o f W ork ., '(a ) In st i tu tio n a nd P rin cip al In ves tig ato r sh all co nd uc t th e c lin ic al s tu dy e ntit led "'E ff ic a cy a nd T ole ra bili ty

o f O lan z ap in e , Que tiap in e and R isp e r id cn e in th e T rea tm en t o f fir s t E p iso d e P sy c ho s is : A R and om ize d D oub leB lin d 52 W eek C om pa riso n " (th e "S tu d y ") in ac co rd an c e w ith th is A greem en t, P ro to co l N um ber S077IUOU4in co rp o ra te d by re fe ren ce h e re in and a s m ay b e am end e d (th e "P ro to co l"), g o od c lin ica l a n d m ed ic a l p ra c tic e : an d a lla pp lic a ble law s, ru le s , reg ula tio ns a nd g uid elin es re la t in g to th e c on du ct o f c lin ic a l in ves tig atio ns . in clu din g. w ith ou tl imi t a t ion , 21 C FR , P a n s 50 ,54 .56 , a nd 312 (th e "A pp lic a b le L aw s") Fo r pu rp o se s o f th is A greem en t, th e te rm"In sti tu tio n " sh a ll in clu d e a ll o th er em ploy ees . exec u tiv es . o f fic e rs , d ire c to rs . fa c u lty , s ta f f , .an d o th e r a u th o riz e da ge nts o f I ns ti tu ti on

(b ) A stm Zen e ca m ay re ta in c on trac t re s ea rc h o rg an iz a tio n s ("C RO ") to a s s is t A straZ e n ec a in m an ag in g ,m on ito r in g a nd o th e rw ise a ss is t in g w i'th th e S tu dy . In st i tu tio n an d P rin cip a l In v es tig a to r ack no wle dg e A stra Zenecasrig h t to a s s ig n o r tran sfe r , in w ho le o r in p a r t. w ith ou t th e co n sen t o f th e in s ti tu t io n o r P rin c ip a l In v es tig a to r , a n y o fi ts r ig h ts o r O blig a tio n s un d e r th is A greem en t to a ny su c h C RO . In s ti tu t io n sh a ll p e rm it su c h C RO to p e r fo rm any o ra ll o f A stru Zen eca 's o blig atio ns u nd er th is A gree men t.

2. P r in c ip a l ln v es tie :a to r. P r in c ip a l In v e s tig a to r rep re sen ts th a t h e o r sh e h a s rea d an d und e rs tan d s th eIn v e s tig a to r 's B ro c hu re fo r th e P ro to co l. P r in c ip a l In v e s tig a to r sh a ll s u p e rv ise th e w ork o f a ll p e rso n s w ho as s is t inp e r fo rm ing th e S tu dy . P r io r to th e c om menc em en t o f th e S tu dy , In s t itu tio n sh a ll d e liv e r to A straZ e n ec a tru e .c om ple te and co rrec t co p ie s o f P r in c ip a l In v es tig a to r 's in v es tig a to r s ta tem en t o n Fo rm l572 an d curriculum vitae.e ac h o r w hic h sh a ll b e s ig n ed by P rin c ip a l In v e s tig a to r. D ur in g th e S tu d y , In s ti tu t io n sh a ll im med ia te ly no r ifyA stra 'Z en ec a in w rit in g a t su c h tim e as it b ec om es aw are th a t P rin cip a l In v e s tig a to r p lan s to lea v e In stitu tio n o r sh a llb e un ab le to com ple te th e S tu dy . I f ' In s t itu tio n an d A straZ e n e ca a re u n a b le to a g ree on a n acc ep ta b le su b sti tu tein v e s tig a to r w ith in f ifte e n (15) d ay s fo llow ing su ch no tic e , th is A greem en t m ay b e te rm in a te d by A straZ en e cap ursu an t to S ec tio n 23 h ereo f.

3 . R e p re s en ta tio n s , W arran tie s an d C o ven an ts . In s t itu t io n rep re se n ts . to A straZ en ec a , a n d P r in c ip a lIn ves tig ato r re p re s en ts , to A straZ en e ca (to th e ex te n t th a t su c h re p re s en ta tio ns . re la te 10 P r in c ip a l I n ve st ig a to r ),


5/61

(c) Neither Insti tut ion, Principal Investigator, nor any other person who assists in performing the Study issubject to any conflicting obligations or anything that might interfere with the performance of the Study or that mightimpair the acceptance of the resulting data by the U .S Food and Drug Administration ("FDA"),

(d) Institution, will not use the services of any person, including Principal Inves t iga tor , who is debarred orproposed for debarment under the Federal Food, Drug and Cosmetics Act in connection with this studv. Inst itutionWill promptly notify Astra.Zeneca it any person v.:hoassists in performing the Study becomes so deba~d

4. Facili tj~!i' Insti tut ion and Principal Investigator shall conduct the Study at the facil ity first identifiedabove, or such other facilities as Astra'Zeneca and Institution and/or Principal Investigator may agree in a separatewritten agreement, and as shall he listed on FDA Form 1572 (the "Facility"). Institution shall make available allpersonnel, facilities and resources necessary to efficiently and expeditiously accomplish its responsibilities under thisAgreement .

5 Subject EnrQIImem and lnformed Consent.(a) Principal Investigator shall enroll subjects into the Study in accordance with Exhibit A (each, a

"SUbject") Principal lnvcsugaior shall use best efforts 10 complete all enrollment by the Patie~t Enrollment ClosingDate set forth in Exhibit A. 'The Study period may be extended or shortened and/or the number of Subject '>Institution may enroll in the Study may be changed, at AstraZeneca's sole discretion.

(b) Principal Investigator shall obtain the informed consent of each of the Subjects prior to any screening orparticipation in the Study and in accordance with Applicable Laws. An informcd consent form that has beenreviewed and approved hy AstraZeneca shall be completed for each Subject,

6 Cornpcllsalion. For the services to be rendered hereunder, AstraZeneca shall pay Institution inaccordance with (he budget, payment schedule, and procedures set forth in Exhibit A. Any amounts paid byAstraZeneca to Institution for reimbursable expenses not used by Institution [0pny the applicable expenses shall bepromptly returned to Astra 'Zeneca. Institution acknowledges and agrees that the payments made by Astrazenecarepresent Asirazcneca's total obligations under this Agreement and fully cover the costs of conducting the Study,except with respect to those expenses reimbursable under Sections 19 and 23(d) hereof.

7 Finandal Disclmure Information At AstraZeneca's request, Principal Investigator shall promptlyprovide to Astr:tZcneca financial disclosure 'statements in compliance with 21 CFR Part54, in the form required byAstra'Zeneca and executed by Principal Investigator and any subinvestigators and such other financial information asAstraZeneca may reasonably request, During the term of the Study and for a period of one (I) year thereafter.Principal Investigator and any sublnvcstigators shall promptly notify A~traZeneca of any changes in or additions tosuch financial information.

8. Ownership ant! ClJntrol of Study Drug. All Study Drug supplied to Institution shall remain the exclusiveproperty of AstrnZeneca until admi~jslered or dispensed to Subjects during the course of the Study. The Study Drug'shall only be used as described in the Protocol in compliance with Applicable Laws. Upon termination orcompletion of the Study. Institution shall, at AstraZeneca's direction, either return to AstrdZeneca or dispose of anyquantities of unused Study Drug, in accordance with Astra'Zeneca's instructions. lnsntution shall maintain completeand accurate records relating to the disposition of the Study Drug supplied to Institutionat Astra7,.eneca's expense

9. Disclaimer. Without limiting AstraZeneca's obligations under Sections 18 and 19 hereof,A ST RA ZE NE CA D OE S H ER EBY D fSC LA lM A NY A ND A LL R EPR E,)E NT AT 10N S A ND W A RR AN TlE S,W H ETH ER W R IT IE N O R O RA L, O R EXPR ESSE D O R IM PU ED , wrra R ESPE CT T O T HE ST UD Y D RU G.I NCLUD ING wrrnotrr L lM ITA T IO N , A N Y R E PR E SEN TA T IO N O R W AR RA N TY O F QU A L ITY ,P E RFO RM A NC E, M ER CH AN TA BIU TY O R FlT NE SS FO R A PA RT IC UL AR U SE O R PU RPO SE , O R T HA TT I1E U SE O F THE srtrov D RU G FO R P UR PO SE S O TH ER T HA N S PE CiFIE D IN T HIS A GR EE M EN T W IL LN OT IN FR IN GE T IIE R IG HT S, P i\T EN T O R O TH ER W IS E, O F A .N YT H IR D P AR TY .

2UM SPA 0077


6/61

1 0. R e co rd s; Reoorts;and R e gu la to rY A s si st an ce .(a ) In s titu tio n sh a ll p re p a re . m ain ta in . a n d re ta in com ple te , c u rre n t, a c c u ra te , o rg an iz e d an d le g ib le S tu d y

D ocum en ta tio n in a m an n e r a c c ep ta b le fo r th e co lle c tio n o f d a ta fo r su bm iss io n to , o r re v iew by . th e FD A an d o th e rre g u la to ry o r g o v e rnm en ta l a u th o r itie s , a n d in fu ll c om plia n c e w ith th e S tu d y an d a ll A pp lic a b le L aw s. Fo r p u rp o s e so f t hi s A g re em e n t:

(i) "S tu d y D ocum en ta tio n " in c lu d e s a ll re c o rd s , s tu d y p e rso n n e l 's w ri tte n a c co u n ts a n d re p o r ts a n dd a ta re la tin g to th e S tu d,'. w he th e r in w ritte n , e le c tro n ic , v id eo o r o th e r ta n g ib le fOI m

(ii) "S ou rc e D oc um en ts" in clu de s a ll re co rd ed o rig in al O bse rv atio ns a nd n ota tio ns o f c lin ic al a ctiv itie sa n d a ll re p o r ts a n d re co rd s n e c e ssa ry fo r th e ev a lu a tio n an d re co n s tru c tio n o f th e S tu d y . re g a rd le s s o f fo rm

(b ) . In s titu tio n sh a ll p ro v id e to A s traZ en e c a d o cum en ta tio n v e r ify in g re v iew lin d ap p ro v a l b y anIn stitu tio na l R ev ie w B oa rd a pp ro ve d by In s titu t io n ("IR B"), o f th e P ro to co l. th e In v e s tig a to r 's B ro ch u re , n n d th ein fo rm atio n to be p ro v id ed to p o te n tia l su b je c ts o f th e S tu d y to se cu re th e ir in fo rm ed co n sen t; o r ig in a l c a s e re p o r tfo rm s fo r e a ch S u b je c t p a r tic ip a tin g in th e S tu d y : a n d su ch o th e r reports w hen an d a s requ ire d b y th e S tu d y o rA pp lic a b le L aw s. In s titu tio n sh a ll p ro v id e th e f in a J d a ta a n d re p o r ts requ ire d by th e Study n o la te r th a n !lie D ataC om ple tio n D ate se t fo r th in E xh ib it A o r su ch la te r d a te a s A stra 'Z en e c a m ay requ ire .

(c ) A t th e requ e s t a n d exp en se o f A s traZ en e c a , In s titu tio n an d P rin c ip a l in v e s tig a to r sh a ll (i) a s s is tA straZ en e c a in th e p re p a ra tio n an d su bm iss io n o f in v e s tig a tio n a l n ew d ru g ap p lic a tio n s , n ew d ru g ap p lic a tio n s . a n dan y o th e r p re rn a rk e t a p p lic a tio n re la tin g to th e S tu d y an d m ark e tin g ap p lic a tio n s re la tin g 10 th e S tu d y D ru g , a n d (ii)a tte n d m ee tin g s w ith th e FD A an d o th e r re g u la to ry o r g o v e rnm en ta l a u th o r itie s re g a rd in g su ch ap p lic a tio n s an d th ea s so c ia te d a p pr ov a ls .

11 . A ud it a n d R ev iew . A straZ en e c a o r its a u th o r iz e d re p re se n ta tiv e s s h a ll h a v e th e r ig h t, u p o n ad v an c en otic e. a t it s exp en se , a n d d u r in g re g u la r b u s in e s s h o u rs a n d a t tim es m utu a lly ag re ed u p o n , to : (a ) a u d it a ll Fa c ilit ie su sed in p e rfo rm an c e o f th e S tu d y ; (b) m on ito r th e co n d u c t o f th e S tu d y ; (c ) re v iew , c o p y ~n d au d it a ll S tu d yD ocum en ta tio n ; a n y o th e r b o o k s , re c o rd s , d a ta a n d W ork P ro d u c t (a s d e f in ed in S e c tio n 14(c ) b e low ) re la tin g to th eS tu d y o r th e r R B ; an d ' a ll re qu ire d lic e n se s , c e r tif ic a te s a n d a c c re d ita tio n : (d ) re v iew an d au d it n I l S o u rc eD ocum en ts ; a n d (e ) in te rv iew P rin c ip a l In v e s tig a to r a n d o th e r p e rso n s w ho a ss is te d iii p e rfo rm in g [h e S tu dy

12. C h an g e s to th e P ro to co l. N o ch an g e in th e P ro to co l sh a ll b e m ad e b y In s titu tio n o r P r in c ip a lIn v e s tig a to r . su b je c t to a n y A pp lic a b le L aw s re la tin g to th e sa fe ty o f re se arc h su bje cts th at. re qu ire a -d ev ia tio n [ro mth e P ro to co l. in w h ic h c a se In s titu tio n sh a ll im m ed ia te ly n o tify A stre .Z en e c a an d th e IR B o f th e fa c ts n e c e ss ita tin gsu ch d ev ia tio n a s so o n a s th e fa c ts a re k n o w n to In s titu tio n , A s tra 'Z en e c a m ay a t a n y tim e m ak e ch an g e s in rh eP ro to co l u po n fiv e (5) d ay s ' a d v an c e w ritte n n o tic e to In s titu tio n ; p ro v id ed , h ow ev e r , th a t, u n le s s th e ch an g e s a rerequ i re d . b y A pp lic a b le L aw s, d o n o t m ate r ia lly in c re a se th e co s t o f p e rfo rm an c e o f th c S tu d y b y In s titu tio n o r a reo th e rw ise ag re ed to b y In s titu tio n , In s titu tio n m ay te rm in a te th is A gre em en t p u rsu an t to S ec tio n 23.

13. , R eg u la to ry In sp e c tio n s . I f a n y g o v e rnm en ta l o r re g u la to ry au th o r ity (a ) c o n ta c ts In s titu tio n o rP rin cip al In ve stig ato r w i th re sp ec t to th e S tu d y . (b ) c o n d u c ts , o r g iv e s n otic e o f its in te n t to co n d u c t, a n in sp e c tio n a ta n y Fac ility , o r (c ) ta k e s , o r g iv e s n o tic e o f its in te n t to ta k e , a n y o th e r re g u la to ry a c tio n w ith re sp e c t to a n y a c ti vi tyo f In s titu tio n . th e IR B, o r P rin c ip a l In v e s tig a to r w h ic h co u ld re a so n ab ly b e exp e c te d to im pa c t a n y d a ta o r c l i n ic a la c tiv ity u n d e r th e S tu d y , In s titu tio n sh a ll p rom ptly n o tify A s tra .Z cn c c a o f su ch co n ta c t o r n o tic e u n le s s th eg o v e inm en t o r re g u la to ry au th o r ity s ta te s a p re fe re n c e to th e co n tra ry . A siraZ en c c a sh a ll h a v e th e r ig h t to b e p re se n ta t a n d to p a r tic ip a te in an y su ch in sp e c tio n o r re g u la to ry a c tio n w ith re sp e c t.to th e Study. In stitu tio n s ha ll p ro vid eA straZ er ie c a w ith co p ie s o f a ll p e r tin e n t in fo rm atio n an d d o cum en ta tio n is su ed b y an y g ov e rnm en ta l o r re g u la to .ryau th o r ity a n d a n y p ro p o s ed re sp o n se . A s traZ en e c a sh a ll h a v e th e r ig h t to re v iew an y re sp o n se s w hic h m ay b erequ ire d an d w hic h p e r ta in to th e S tu d y , N o su ch re sp o n se sh a ll c o n ta in an y ra i s e o r m is le a d in g in fo rm atio n w ithre sp e c t to th e S tu d y , th e S tu d y D ru g o r A st raZ .e n e c a

14 O w ne rsh ip o f E qu ipm en t, In te lle c tu a l P ro p e r ty an d W o rk P ro d u c t.(a ) A ll m ate r ia ls , d o cum en ts . d a ta , so f tw are an d in fo rm atio n su p p lie d to In s titu tio n b y A srraZ cn c c a o r

p re p a re d , .d e v e lo p ed o r g en e ra te d b y o r o n b eh a lf o f in s titu tio n , in c lu d in g h u t n o t lim ite d to S o u rc e D ocum en ts a n d

3UM SPA 0078

1: ; -17


7/61

S tudy D ocum en ta tio n (e xc lu d in g reco rd s w hich a re solely p at ie nt s' m e dic al records) in co nn rc tiu n w ith th e . .S tu dy o rth e p e r fo rm an ce o f i ts o h lig a tio n s und e r th is A g reem en t (th e "P rop e rty ") sh a ll b e a nd rem a in th e p ro p e rty o fA straZ en e ca p ro v id e d th e In s tiru t io o m ay re ta in a c opy o f a ll m ate r ia l , d o cum en ts , d a ta and in fo rm atio n p rep a re d ,d ev elo ped o r g en era ted under this Agreement in o rd e r to pub lis h in ac co rd an c e w ith this Agreement. A ny su chP rop e rty sh .. 11 be d e liv e red to k traZ en e ca hy In s titu tio n im m ed ia te ly UPOIl d em and and a t A sn -aZ en eca 's e xp en se .Fo r p urp ose s o f th is S ec tio n 1 4, " A st ra 'Z e n ec a " s ha ll i nc lu d e a ny d es ig ne e o f A s tr a.Z e ne ca , i nc lu d in g an y d i rec t 01indirec t a ff il ia te o f Astra 'Zeneca p ic .

(h ) A ma7 .en eca sh a ll ow n a ll rig h t, t it le an d in te re s t in and to any equ ipm en t su pp lied by, o r p u rc h as ed !II.th e exp en se o f , !\s traZ en eca (th e "Equipment"), unless otherwise s pe cif ic all y a ck no w le dg ed hy Astra'Zeneca inw rit in g . In s t itu tio n sh a ll m ak e any Ilee or o th e r f il in g s n ece s sa ry to secure an d ev id en ce A straZ en eca 's o wn ersh ipo f th c E qu ipm en t as and w h en r eq ue ste d by A:ma7 e n e c n . institution shall (i) L ISC lh e E qu ipm en t o n ly Cor th epu rp o se s d esc r ib ed in th e S tu dy o r su ch o th e r p u rp o se s a s A straZ en eca m ay app rov e in w ritin g , (i i) re s tr ic t a c ce ss toand u se o f the E qu ip men t to P rin cip al Investigator and o the r personnel fo r w hom su ch acce s s and u se is requ ired toconduct th e S tu dy , an d (iii) d e liv e r th e E qu ipm en t to Astrazeneca o r its d e s ig n ee on th e ea rl ie r o f th e . completion o rth e S tu dy , th e te rm in a tio n or exp i ra t ion of th is A g reem en t. o r as o the rw is e requested by Astrnz.eneca a tAstraZenecas expense .. A straZ en eca w ill be re spons ib le for tlie ma i n t e n a n c e of t hi s e qu ip m e n t

(c ) E ach p a rty sh a ll re ta in a ll rig h t, t it le an d in te re s t (c o lle c tiv e ly . "R ig lits~) in a ny parent, parentapp lic a tio n , trad e se c re t . k n ow -how and o th e r in te l le c tu a l p ro p e rty th a t w as ow ned by such p a rty p rio r to th e d a te o fthis Agreement and no lic en se g ran t o r a ss ig nm en t, e xp re ss o r im plied , b y es to pp e l or o th e rw ise . is in ten d ed b y . o rsh all b e in fe rred fro m, th is A greem en t.

(d ) T he p a r tie s recogn ize th a t in v en tio n s and d isc ov e rie s , k now -how , trad e -sec re ts an d o th e r in te l le c tu a lp ro pe rty , in clu din g im pro vem en ts , w he th er patentable o r no t, m ay h e con ce iv ed , red u ce d to p rac tic e o r o th e rw isem a d e by In s ti tu t io n, P rin c ip a l In v es tig a to r o r any o th e r p e rso n w ho a ss is ts in p e rfo rm ing th e S tu dy (w he th e r so le ly o rjointly w ith o th e rs ) (ea ch , an "Inventor") in conn ec tio n w ith th e S tu dy or the performance of o blig atio ns u nd er th isA greem en t C ln v en tio n s"). A straz .e n eca sh a ll o w n a ll R ig h ts [0 eac h In v en tio n , an d in s ti tu t io n sh a ll c au se eac hIn v en to r p rom ptly to ta k e any ac tio n s n ece sso ry to a s s ig n an d tran s fe r su ch R igh ts to A straZ en eca , in c lu d in g bu t n o tli m ite d to th e. I ollo w in g:

{i) d is c lo s e to A straZ cn eca in w ritin g the conception, red u c tio n to practice o r m ak in g o f su chIn ven tio n; an d

(ii) w ith ou t a dd it io n a l co n s id e ra tio n , a ss ig n an d tra n sfe r to AstraZeneca all R igh ts to p a ten ts , p a te n tap p lic a tio n s , an d R igh ts to f ile fo r p a ten t p ro tec tio n fo r su c h In v en tio n th ro ug hou t th e w orld , an d p rov id e su chdocurnenranon and t e s t imony as Asuazencca m a y re aso na bly re qu ir e in conn ec tio n w ith th e app lic a tio n th e re fo r andp ro se cu ti on t he re of.

(c) In s ti tu t io n sh a ll fu lly d isc lo se to AstraZcneca all w o r k , reports, wnungs, ideas, d es ig ns , m eth od s,com pu te r so f tw are and d a ta reco rd ed in any fo rm th a t a re c re a ted . d ev e lo p ed , w ritten , co n ce iv ed o r in v en tio n s o rd isc ov e rie s m ad e by In s titu tio n , P rin c ip a l In v es tig a to r o r any o th e r p e rso n (w he th e r so le ly o r jo in tly w ith o th e rs) a s are su lt o f o r in conn ec tio n w ith th e S tu dy o r th e p e r fo rm an ce o f th e ir o b lig a tio n s und er th is A greem en t (co lle c tiv e ly ,"W ork P rodu c t"). In s t itu tio n 'an d P rin c ip a l In v es tig a to r each h e reby irrev o cab ly a ss ig n s , o r In s t itu tio n sh a il c au seP rin c ip a l In v es tig a to r a nd eac h o th e r p e rso n to ir rev o cab ly a ss ig n , to A stra 'Z en eca a ll o f th e ir re sp ec tiv e r ig h ts . t it le sand in te re s ts w orld w id e in and to su c h W ork P rodu c t S u ch as s ig nm en ts sh a ll in c lu d e the r ig ht to a ll causes o f a ct io nfo r c op yr ig ht i nfr in ge m en t of any su ch W ork P rodu c t. in c lu d in g , w ith ou t l im ita tio n , th e rig h t to in s ti tu te , p ro ce ss ,d e fend and se ttle any su it o r o th e r leg al o r adm in is tra t iv e p ro c eed in g . to en jo in in f rin g em en t o r m isapp ro p ria tio n o rsu ch W ork P rodu c t. to g e th e r w ith th e so le r ig h t to an y re su lt in g recov e ry o f d am ages , ro y a ltie s , profits, l ega l feesand co sts . . .

(1 ) In s t itu tio n a nd /o r P rin c ip a l In ves tig a to r sh a ll. an d sh a ll c au s e an y In v en to r o r any o th e r p e rso n to , w he rea pp lic ab le a nd c on sis te nt with th e requ irem en ts o f th is A greem en t, (i) exec u te a ll d o cum cn ts and p e r fo rm a ll a c tsd ee m ed n ec essa ry by Am a7 .en ec n to ev id en c e A s traZ en eca 's ow ne rsh ip o f a ny In v en tio n and W ork P ro du c t(in cl ud in g , w i th o ut l imita t ion , th e m ak in g o f any b io lo g ica l d epo sits), an d (ii) a ss is t A straZ en eca in p rep a rin g .p ro secu tin g , o b ta in in g, reg is te rin g, m ain ta in in g . o e rend in g and cn lo rc ln g , a t A maZ en ec a 's 'so le exp en se (fo r ac tu a lco s ts in cu rred ). d isc re t io n and exc lu s iv e con tro l , n i l U nite d S ta te s p a ten ts (in c lu d in g , w ith ou t l im ita tio n , lilly

UM SPA 0079


8/61

divisions. continuations.c.ontinu3tions-in-part. reissues. renewals. extensions or the like of any such patent) and anyforeign patents or equivalents thereof (including, without limitation. cert ificates of invention), copyrights. tradesecret rights and other proprietary rights in and to the Inventions and such Work Product in any and all countries asmay be determined by AstmZeneca. .

(g) Inst itution and Principal Invest igator each hereby irrevocably appoints AstraZeneca, and Insti tut ionshall cause each other Inventor or any other person. where applicable, irrevocably to appoint Astrs 'Zeneca, as its. hisor her, as applicable . at torney-in- fact for the purpose of executing such documents in their respective names as maybe necessary or desirable to carry out the purposes of subparagraphs (a) through (f) hereof.

(h) The parties hereto agree that all activities under this Agreement ("Agreement Activities") shall falloutside the. planned and committed activit ies of any government-funded project undertaken by Insti tut ion and/or.Principal Investigator C"Gcvemment-funded Activities") and shall not diminish or distract from the performance ofsuch Government-funded Activities within the meaning of 37 CFR 40JJ(a)(I), and therefore. that any Inventionmade hereunder shall not be subject to the conditions of 37 CFR Chapter IV, parts 40 I and 404. ln the even! thatAgreement Activities shall be found to be Government-funded Activities. Institution and/or any other Inventor shalltakeall actions necessary to retain tit le to any Invention made under this Agreement. including those required QY37CFR 401 14(c)(1), (2). and (3), In the event that any Inventions or Work Product conceived or reduced topractice, made or developed by any Inventor hereunder are control led by federal law in accordance with 37 CFR 50 LI - 501.11, the parries hereto agree that any license granted to any Inventor to such Invention controlled byfederal law, arising from Agreement Activities shall be worldwide and exclusive, subject to the right of the UnitedStates to retain an irrevocable, royalty-free right to use the inventions throughout the U, S. Government.

15, Confidential Information.(a) For purposes of this Agreement. "Confidential Information" means any information of AstraZeneca.

whether of a technical. business or other' nature, induding,but not limited to, Information that relates 10Astrazeneca's trade secrets. products, promotional material, developments, proprietary rights or business affairs.together with any Inventions. anything marked as Confidential by AstraZeneca. Work Product and all otherinformation collected, prepared, developed or generated by Institution, Principal Investigator and any other person'pursuant 10 this Agreement except as required by Jaw and academic policy. including this Agreement. ConfidentialInformation does not include any information that:

(i) Institution and/or Principal Investigator can prove was known to it prior to the dale of thisAgreement and was not subject to any confidentiality restrictions;

(ii) Institution and/or Principal Investigator can prove was lawfully obtained from a third party withoutany obligation of confidentiality;

(iii ) Is or becomes part of the public domain through no act or violation of any obligat ion of Inst itutionand/or Principal Investigator; or

(iv) Required to be disclosed by law, regulation or court order,. (b) For a period of seven (7) years from receipt of Confidential information, Insti tut ion and/or Principal

Investigator shall not, without AstraZeneca's prior written consent or as may be permitted by this Agreement,disclose to any third. party any Confidential Information, and shall use such Confidential Information solely forpurposes of performing its obligations under this Agreement. Institution shall restrict the dissemination ofConfidential Information to only those persons within i ts organization who have a need to know. and shall ensurethat they are aware of the obligation of confidentiality required by this Agreement and are similarly bound,Institution and/or Principal Investigator shall use at least the same care and discretion in maintaining theconfidentiality of the Confidential Information as it uses with its most sensitive confidential information. Institutionand/;r Principal Investigator shall notify Astra'Zeneca promptly upon Jns'titution and/or Principal Investigator 'sdiscovery of any loss or compromise of the Confidential Information. Upon the termination or expiration of thisAgreement or upon Astra'Zeneca's earlier request, Institution and/or Principal Investigator shall promptly return toAstraZen~ca all Confidential Information.

5UM SPA 0080


9/61

( c) N o t w it hs ta n di ng subparagraph (b) a bov e , if In st i tu tio n a nd /o r P rin cip al I nv es tig ato r a rc le ga lly r eq uire d10 disc lose Conf iden t i a l lnforrnarion an d /o r re su lts o f th e S tu dy , In s ti tu t io n an d /o r P rin c ip a l In v es tig a to r sh a llp rom ptly n o tify A straZ en ec a in w rit in g no le s s th a n f iv e (5) bu s in e s s d ay s p rio r to m a kin g th e r equ ir ed d isc lo su reIn s tiru rlo n a nd /o r P rin c ip a l In v es tig a to r sh a ll c ra f t su ch d isc lo su re a s re a so n a b ly requ es te d by As t r a z e n e c a );0 t ha ts uc h d is cl os ur e sha. l co n ta in on ly su c h C on f id en tia l In fo rm atio n as is requ ired b y A pp lic a b le L aw s. N oth in gcon ta in ed h e re in sh a ll p ro h ib it In s ti tu t io n an d /o r P r in c ip a l In v es tig a to r f rom d isc lo s in g re su lts o f th e S tu d y to th ee xte nt n ec es sa ry 10 p rev en t o r m itig ate a se r io u s h e a lth h aza rd , p ro vid ed , h ow ev er , th a t In s t i tu tio n an dio r P rin cip a lIn v e s tig a to r sh a ll n o tify A straZ en ec a p r io r to m ak in g su ch a d is c lo su re : a n d im med ia te ly a f te r it h a s m ad e su ch ad is c lo su re . '

(d ) W ith re sp e c t to th e S u b jec t ,' m ed ic a l re co rd s , th e p a rt ie s ag ree to h o ld in c on f id en ce th e id en ti ty o f th eS ub jec ts in a cco rd an c e w ith A pp lic ab le L aw s.

16 . R ig ht, to P ub lic atio n.(3) In s ti tu t io n an d P rin cip a l In v e s tig a to r ac kno wle dg e an d ag ree th a t th e S tu dy is b ein g c ond uc te d as p a rt o f

a m ult i-c en te r c l in ic a l tr ia l , th at d a ta from a ll su c h c en te rs w il l b e po oled an d a n a ly z ed , a n d th a t d isc lo su re o f da taf rom a sin g le s i te m ay b e m is lea d in g . T he pu b lic a tio n s a nd p re se n ta t io n s o f d a ta c om ing from th e S tu dy w ill b eg ov e rn ed b y th e p ub lic a tio n s a nd p re s en ta tio n s po licy d e te rm in ed by th e s tee rin g com m itte e o f th e S tu d y w hich w illb e c om p ri se d o r in d iv id ua ls f ro m th e c oo rd in a tin g c en te r (U niv ers i ty o f N or th C aro lin a a t C hap e l H il l). s itein ves tig ato rs an d rep re s en ta tiv es o f A stra 'Z en ec a. S ub jec t to th is S ec tio n 16, I ns ti tu ti on a nd P ri nc ip al I nv es tig at orm ay subm it fo r p u b lic a tio n any m anu sc r ip t , a b s tra c t o r o th e r d o cum en t, an d p re s en t a t an y m ee tin g , a n y d a tag en e ra te d o r a r is in g from th e p e rfo rm an ce o f (h is A greem en t a fte r A straZ en ec a o r its d e s ig ne e pu blis h e s a n a r t ic le o nth e S tu dy o r a f te r tw en ty -fo u r (24) m on th s h a v e e lap se d sin c e th e com ple tio n o f th e S tu dy a t a l l s ite s , w hich ev e ro ccu rs fir s t; p ro v id ed , h ow ev e r , th a t n e ith e r In s ti tu t io n no r P rin c ip al In ves tig ato r m ay tak e su ch a c tio n w ith re sp ec tt o a ny p u bl ic ati on Of p re sen ta tio n, o r p or tio n (h ereo f, th at A straZ en ec a d ete rm in es (i) is in v io la t io n o f S ec tio n 15h ereo f, (ii) is n ot c on sis ten t w ith a c~d em ic s tan da rd s, (iii) is fa ls e o r m is lead in g, o r (iv ) is fo r co mm erc ia l p urp o se s

(I In st i tu tio n a nd /o r P rin cip al In ves tig ato r sh all s u bm it a co py o f an y p ro po sed m an usc rip t, a bs tra c t,p re se nta tio n o r o th er d oc um e nt 10 A stra 'Z en e ca fo r rev iew and c om m en t a t le a s t s ix ty (60) d a y s p r io r to itssu bm is s io n fo r p ub lic a tio n o r p re s en ta tio n N o pu blic a tio n o r p re se n ta t io n w ith re sp ec t to th e S tudy sh a ll h e m adeu nle ss a ll A straZ en ec a C on fid en tia l in fo rm atio n h as b ee n rem o ve d. 'In st itu tio n a nd /o r P rin cip al In ves tig ato r sh allc o n s id er in g ood fa ith a ny A straZ en e ca c om m en ts . [f requ es ted in w rit in g b y A stra Zen ec a, In st itu tio n an d/o rP rin cip al In ve stig ato r sh all w ith ho ld m a te ria l f ro m su bm is s io n fo r p ub lic a tio n o r 'p re se nta t io n fo r an ad ditio na ln in e ty (90) d ay s to a llow fo r th e fi l in g o f a p a ten t a p p lic a tio n o r th e ta k in g o f o th e r m easu re s to e s ta b lis h andpre s e rve Asirazeneca's p ro p rie ta ry rig h ts : T o th e e xten t th a t a n y p rov is io n o f th is S ec tio n 16 m ay be in co ns is te nt ina ny re sp ec t w ith any sta tem en ts ab ou t p ub lic a tio n p olic y se t fo r th in th e P ro to c o l, th e p ro vis io n s o f th is S ec tio n J 6s h il l! c o n tr o l.

(c ) In sti tu tio n a nd P rin cip al In ves tig ato r ag ree th at , if e ith er p ub lish es th e re su lts o f th e S tu dy , A straZ en ecais h ereb y g ran te d an ir re vo cab le , ro ya lty -tre e lic e nse [0m ake a nd d is tr ib u te c op ie s o f su ch p ub lic a tio n un de r an yc opy rig h t p riv ileg e s th at In s t itu t io n o r P rin c ip al In v e s tig ato r m ay h a v e . A straZ .e o e ca a lso sh all h a v e th e rig h t topu blis h in d ep end en tly th e re su lts o f th e S tu dy in t he a g gr eg a te .

17 , U se o f N am e; A dve rt is in g .(a ) S ub jec t to A pp lic a b le L aw s, n eith er In s ti tu tio n , P rin cip a l In v e s tig ato r , n o r A straZ en e ca sh a ll m en tio n

o r o th e rw is e u se th e n am e , trad em ark , trad e n am e o r lo go o f th e o th e r in a ny pub lic a tio n . p re s s re le a s e , o rp rom otio n a l m ate ria l w ith re sp ec t to th e S tu dy w ith ou t th e p r io r w rit te n app ro v a l o f th e o th e r p a r ty ; p ro v id e d ,h ow ev e r , th a t A sr ra 'Z e n ec a sh a ll h av e th e rig h t to id en tify In s ti tu t io n as th e s ite a t w hich th e S tu dy w as con du c tedan d to id en tify th ose in div id ua ls re sp on sib le 'fo r co nd uc tin g th e S tu dy .

(b ) ln s tl tu t io n an d Inv es tig a to r sh a ll n o t is su e to th e pu b lic any in fo rm atio n o r s ta tem en t th ro ug h th e p re s s o rany o th e r m ed ia , in c lu d in g hu t n o t lim ite d to adv e r tis em en ts fo r th e e n ro llm en t o f S tu dy sub je c ts w ith o u t th e p rio rw ritte n p e rm is s io n o f A stra 'Z en eca a nd th e re v iew a nd ap p rov a l o f th e IR B

6

UM SPA 0081


10/61

J 8 . I n dem n i fi c at io n py Mtr aZcn e c iL(a ) E xcep t as se t fo rth b e low , A s traZ en~a ag re es to defen d , indem nify an d h o ld ha rm less In stitu tion , it;

o ffice rs , em ploy ee s, a gen ts , an d P rin c ip a l In ve stig a to r (co llec tiv e ly , th e "In s titu tio na l In dem nified P ar tie s") fromand aga in st any an d a ll liab ili ty , c la im s, lo s se s, d am age s an d expenses (co llec tiv e ly , ''1 .o sses") fo r b o d ily in ju ry o rd ea th to S ub je c ts d ire c tly t:au sed b y the adm in is tra tion o f th e S tu dy D ru g if In stitu tio n and P rin c ip a l Inv es tig a to r (i)have com plied w ith th e p rov is io n s o f th is A greem en t, th e P ro toco l a nd a ll w ritten in stru c tion s o f A straZ ene cacon cern ing adm in is tra tion o r u sc o f th e S tud y D rug . (ii) ha ve u se d rea so na ble m ed ic al judg men t in th e a dm in is tra tiono f th e S tu dy D rug , an d" (iii) o th e rw ise ac te d in con fo rm ity with gene ra lly ac cep te d s ta nd ard s o f th e m ed ica lc om m un ity in w hich they p ra c tic e an d w itho u t neg lig en ce o r wil l fu l m iscon duc t. A stra zene ca sh a ll h av e theexc lu s iv e r igh t to re ta in co un~e1 o f it'> c hoo sing 10 represent t h e i n st it u ti o na l In de mn ifie d P art ie s and sha l l retainexc lu s iv e co n tro l o f th e lit ig a tio n , in c lu d ing , w itho u t lim ita tion , th e r igh t to m ak e any com prom ise o r se ttlem en t.prov ided t h at A s t ru e n e. :a sha l l n o! m ak e any se ttle men t admi t t ing f au l t on th e p ar t o f I ns tit ut io n w ith ou t its w ritte nconsen t, su ch co nsen t no t to b e un rea so nab ly w ith he ld ,

(b) As tm7en e c a shall have no o b lig a tion to d efen d , ind em nify or hold h arm less an y Institutionalind em nif ied P a rty un de r th is A g reem en t w ith re sp ec t to a L oss u n les s In stitu tion o r P r in c ip a l Inv es tig a to r ha sp ro v id ed A s t.r aZ e ne c a with w ritten no tice o f such L o ss w ith in f if teen (15) bu sin e ss day s o f rec e ip t o f a ny c la i m o rsui t relating 10 a L oss. T he In s titu tio na l Indem nif ie d P ar tie s sha ll a llow A straZ enec a to assum e the d efen se of ~Ilysuch L o ss , in c lu d ing the r igh t to se le c t d efen se co un se l an d the ri gh t t o s et tle a n y L oss a s se t forth abo ve , and shallcooper a te fully w ith A srra .Z cncc a a nd its a ge nts a nd re presen ta tiv e s in th e in ve stig ation an d de fe nse of su ch L os s.

(c ) T erm in a tio n o r exp ira tion o f th is A gre em en t an d th e S tu dy sha ll no t a ffe c t A strnZ ene ea 's ob lig a tio n s toth e In stitu tion al Ind em nif ied P artie s. ....~t h respect to a ny c la im o r law su it b ased up on adm in istra tio n o f th e S tu dyD ru g un de r th e c irc um stanc es se t fo rth ab ove p r io r to In stitu tion 's an d P rin c ip a l In ve stig a to r 's re ce ip t o f no tice o fte rmina t ion .

19. Su b je< et..lc i!!!:Y . A straZ ene ca sha ll re im bu rse In stitu tio n fo r th e d irec t, re asonab le , a nd nec essa rym e di ca l e xp en se s lor th e trea tm en t o f an y bo d ily in ju ry th a t is a d irec t resu lt o f th e adm in istra tio n o f th e S tud y D rugif (i) In s titu tion an d P rin cip a l In ve stig a to r h av e c om plied w ith th is A gre em en t. th e P ro to co l, a ny w ritten in s tru c tion so f A straZ enec a conc ern ing thc S tud y , a nd a ll A pp lica b le L aw s, (ii] th e S tu dy D ru g w as taken as p re se t ib c d , (i ii) a llth e requ irem en ts o f in fo rm ed co nsen t have b een com plied w ith in ac co rd anc e w ith 5(h ) h ereo f, (iv ) th e injury w asno t de lib e ra te ly c au sed o r a resu lt o f the n eg lig en ce o r w illfu l m is co nd uc t o r In s titu tion o r P rin c ip al In ve stig a to r, (v )P r in c ip a l Inve stig a to r w as im med ia te ly no tif ie d o f th e in ju ry , an d (v i) th e m ed ic a l ad v ice o f P r in c ip a l Inv es tig a to rw as fo llow ed . C om pensa tion fo r lo s t w age s o r an y o th er dam ag es , expen ses , o r lo s se s, o r fo r m ed ica l expen se ,w h ich h av e been cover ed by a subjecf's m ed ica l o r o th e r in su ran ce w ill not h e reimbursed by Ast ra 'Zcncca ,

2 0. In de m nific atio n h y In stitu tio n,(11) In stitu tion sha ll d efen d, ind em nify an d ho ld ha rm less A ~tra Z.en ec a a nd irs o ff ic ers , d ire cto rs , p a rtn ers ,

em ploy ee s an d agen ts ("A straZ enec a In dem nified P ar tie s") from and ag a in s t any and a ll L o sse s cau sed by a b re ac ho f this A greem en t by an In stitu tio na l In dem nified P a rty , in c lu d ing , w itho u tlim ita tion , th e n eg lig enc e o r w illfu lm i s c o n d u c t of In s titu tion . P rin c ip a l In ve stig a to r , o r a ny o the r p erso n w ho a ss ists in p erfo rm ing the S tu dy , inp erfo rm ing the ir ob lig a tion s !!!lp e r th is A g;re em ep l o r c au sed by the fa ilu re o f In s titu tion . P r in c ip a l Inv es tig a to r, o ran y o th er pe rson w ho assis ts in p erfo rm ing th e S tudy , ~2_!:om ply w ith th e p ro v isio n s o f th is A greem en t, Jh e P ro tO CO l,an y \lL r iH en in stru c tion s o f A s traZ en ec a con cern ing the S tud y o r ~y A pp lic ab le L aw s, N o tw ith sta nd ing theforegoing, In s titu tion sha ll h ave no ob lig a tio n pu rsuan t to th is A greem en t to de fend , in dem nify o r ho ld h arm le ss a nA s tra 'Z e ne ca In de m ni fi ed Party from an y L osses to th e exten t c au sed by a b rea ch o f th is A g re em en t by anA s tra Z eJ :le ca In de m ni fi ed P ar ty , in cl ud in g hy s uc h p ar ty 's n eg lig en ce o r w illfu l m isc on du ct.

(b) In stitu tio n sh all h av e n o o blig atio n IU d ef en d, i nd em n if y Of h old h arm le ss a ny A S lrd lin er.:a In de rn nif ie dP a rty un de r th is A greem en t w ith respe c t to a L oss un le ss th e p ar ty se ek ing ind em nif ic ation (i) p ro v id e d I ns ti tu ti onw ith p rom pt, w ritte n no tice o f su ch L oss an d (ii) co ope ra tes f u l l Y w ith In stitu tio n a nd its a ge nts a nd re pre se nta tiv esin th e inv es tig a tio n an d de fense o f such T.o ss .

7UM SPA 0082


11/61

21. I nsurance.(3) In s t i tu t io n sh a ll m ain ta in du r in g th e te rm o f th is A g reem en t a rid fo r a p e rio d o f th ree (3) yea rs

the rea f t e r , the I ul lo w in g in su ra nc e c ov er ag e:(i) C om m erc ia l G en e ra l L iab ili ty fo r b od ily in ju ry an d p rop e rty d am age (inc luding 10" o f u se thereof)

w ith m in im um lim its 0[$1,000,000 e ach o c cu r re n ce a nd $2,000.000 g en era l a gg reg ate . in clu din g P rem ise s L iab il ity ,P ro d u c ts /C om ple ted O pe ra tio n s , an d C on tra c tu a l L ia b ili ty c ov e rag e fo r th e in d em n ity p ro v id ed u nd e r th isAg r e emen t ;

(ii) Wo r ke rs ' C o m p en sa tio n as required by a ll A pp lic ab le L aw s a nd Em ploy e r 's Liabi l i ty c ov e r a g ew ith a lim it o f n o t le s s th an $[,000,000; an d

(ii i) M ed ica l M alp ra c tic e P ro fe ss io n al L iab il i ty in su ran ce a s requ ire d b y M inn eso ta S ta te law ,(b ) E ach o f th e a bov e po lic ie s o f in su ran c e sh a ll b e p rim a ry to a ny lia b ili ty in su ra n ce carried by

A s traz cn c ca w hic h in su ran ce (s ) sh a ll b e exces s a nd non -con tr ib u to ry fo r c la im s and lo s se s a r is in g ou t o f th ep erfo rm a nc e o f th is A g re em e nt,

(c ) In st itu t io n sh alt, a t A straZ en eca 's requ est . h a v e its in su ran c e ca rr ie r o r ea rn e rs , o r w ith re sp e c t to a s e lf-insu rance p rog ram h a v e a n app rop ria te o f fic e r o f In s t itu t io n , fu rn ish to A straZ en ec a c e rt ific a te s th at al l i n su rancerequ ired und e r th is A gre em en t a re in fo rce , su ch ce r tif ic a te to in dic a te any d e du c tib le and /o r se lf -in su re d retentionIns t i tu t ion sna i l im m ed ia te ly p ro vid e A straZ en eca w ith w rit te n n otic e o f any can ce lla tio n , n on -ren ew al, exp ira t io n o rm a te ria l m o dif ic at io n o f a ny r equ ir ed in su ra nc e o r se lf -in su ra nc e.

I22. T erm . T h is A greem en t sh a ll be effective a s o f M arc h 18, 2002 a nd sh all c on tin ue until t he e a rl ie r ofthe dare that tbe final S t udy D ocum en ta tio n h as b een p rov id e d to A straZ en e ea fo llow ing com ple tio n of th e S tu dy a ndth e d a te th a t th is A greem en t is terminated in a cco rd an ce w ith S ec tio n 23,

23 . Te rm i n a t i o n .(a ) T h is A gre em en t m ay b e te rm in a ted o r su sp en d ed by A st.raZ en eca im med ia te ly upo n w rit te n n o tic e to

In s t i tu t io n fo r sa fe ty co nce rn s o r a s otherwise requ ired b y A pp lic a b le L aw s, A straZ en eca and In s ti tu t io n re se rv e th er igh t to terminate th is A gre em en t a nd S tu dy at any tim e in its so le d isc re tio n upo n th irty (:30) d a y s prior wri t t enno tic e , H ow ev e r , A straZ en e cam ay te rm in a te th is A gre em en t an d Study upon f iv e (5) d ay s p rio r 'mitten no t i c e forsafety, regulatory or e th ic al r ea so n s:

(b ) T h is A g reem en t m ay b e te rm in a ted o r su sp end e d b y ln s titu t io n im med ia te ly upo n w r itten no tic e toA~ t raZenec [ l (i). fo r s a fe ty con ce rn s o r a s o th er w is e requ ire d by A p p lic a b le L aw s. o r (i i) if Ast raZene c a ma k e sc h a ng e s 10 th e S t udy tha t a re no t requ ired b y A pp lic ab le L aw s a nd no t ag reed to by In s ti tu tio n an d such c h a ng e smateria l ly in c rea se th e c o st o f p e rfo rm an c e o f th e Study by In s titu t io n . T his A greem en t m ay b e te rm ina ted byIn sti tu tio n, in i ts s ole d is cre tio n, o n th ir ty (30) d ay s p rio r w r it te n n otic e to A stra 'Z en ec a

(e ) U pon no tic e o f te rm in a tio n , In s t itu t io n sh a ll im med ia te ly c ea s e e n ro llm en t o f S ub jec ts in to th e S tu dyand , a t th e e lec tio n o f A straz en e ca , sh a ll (i) te rm in a te th e S tu dy w ith re sp ec t t() th e en ro lled S ub je c ts in an o rd e rlyand p rum pt m ann e r and p ursu an t to con su lta tio n w ith A straz en ec a 's c lin ic a l m on ito r , in c lu d in g , w ith o ut l im ita tio n ,an 'y requ ired fo llo w -u p trea tm en t w ith p rev io usly en ro lle d S ub jec ts ,

(d ) E xce p t in th e ca s e o f te rm in a tio n as a re su lt 'o f an un c u re d b rea ch o f th is A greem en t b y In s titu t io n ,A str aZ en ec a sh all (i) re im bu rs e In s titu t io n fo r i ts re a so n ab le d ire c t co s ts in cu r re d in c onn ec tio n w ith tra n s fe r o fS ub jec ts p ursu an t to S ec tio n 23(c) abov e, an d (ii) w ith re sp ec t to S ub je c ts w ho h a v e nu l com ple ted th e S tu d y a t th e, d a te o f th e te rm in a tio n o f th is A g reem en t, m ak e p aym en ts to In s ti tu t io n in ac co rd an ce w ith E xh ib it A fo r w orka lre ady p e rfo rm ed in ac co rd an ce w ith th e S tu dy .

(e )' W ith in th ir ty (30) d ay s a fte r th e te rm in atio n o f th is A greem en t, In st itu t io n sh a ll d e liv er to A straze n ec aa f in a l ac cou n tin g o f a n S ub je c ts p a rt ic ip a ti n g in th e S tu dy a nd th e v is its com ple te d in acc o rd an c e w ith th e S tu d ydu rin g th e te rm o f th is A gre em en t, a n d a ll re a so n a b le d ire c t co s ts in cu r re d in co nn e c tio n w ith a ny tran s fe r o f th e

8UM SPA 0083


12/61

S tu d y . W ith in Io r ty -f iv e (45) d ay s o f d e liv e ry o r re c e ip t o f th e f in a l a c co u n tin g , e ith e r Inst i tu t ion sh a ll re fu n d toA straZ en e c a an y excess amounts paid by A straZ en e c a o r A straZ en e c a sh a ll p ay an y ad d itio n a l am ou n ts ow ed toI n st it u ti o n, a s th e c a se m ay b e , .A .s rraZ en e c a o r i ts d e s ig n e e sh a ll h av e th e r ig h t for a p e r io d o f tw o (2) y ea rs a ft er th ep aym en t o f an y tra n s fe r c o s ts to au d it In s titu tio n 's b o o k s an d re co rd s w ith re spe c t to su ch a c cou n tin g .

24. ln de pe nd en t C on tr llc to L In under tak ing 10 per fo rm i ts se rv ic es h ere un de r. In stitu tio n a nd P rin cip alI nves t ig a to r are d o i n g 50 as i n d ep en d en t contractors, an d nO I a s em plo y e e s o r a g en ts of Astr a 'Zeneca , N o p ar ty s ha llre p re se n t its e lf a s a n ag en t o f a n y o th e r pa r r y .

25. A ,s ig nm en t N o p a r ty sh a ll a s s ig n th is A gre em en t o r an y o f its r ig h ts o r O blig a tio n s h e re u n d e r w ith o u tth e p rio r w r itte n consent o f th e o th er p ar tie s, except th a t Astrazeneca. w ith ou t th e consent o f an y o th e r p a r ty h e re to .m ay a ss ig n th is A g re em en t (a ) in co n n e c tio n w ith th e tra n s fe r o r sa le of a ll or su b s ta n tia lly a ll o f its a s se ts o rb u s in e s s o r its m erg e r o r c o n so lid a tio n w ith an o th e r c om pan y , o r (b ) to an y d ire c t o r in d ire c t a ff il ia te o f AstraZenecap lc ,

2 6. S e v er ab il it y. If any p ro vis io n o f this A gre em en t sh all be he ld 10 b e ille g a l, in v a lid , o r u n en fo rc e ab le inw ho le o r in p a r t fo r a n y re a so n , th e rem ain in g p ro v is io n s sh a ll c o n tin u e in fu ll fo rc e an d e ffe c t, a n d th e p a r tie s sh a llsub s t i tu te a le g a l. v a lid , a n d en fo rce ab le p ro v is io n w ith te rm s s im ila r to su ch provision as m ay b e p o ss ib le a n dreasonably a cc ep ta ble to th e p an ic s

27 . T his se clio n in te ntio na lly o mitte d.28. N o tic e s . A n y requ ire d n o tic e o r o th e r c om mun ic a tio n sh a ll b e in w ritin g an d sh a ll b e d e em ed g iv en

on ly if d e liv e re d p e rso n a lly o r se n t b y a telecopy (w ith tra n sm iss io n co n firm ed ) o r b y re g is te re d o r c er tif ie d m ail.returnreceipt requested an d p o s ta g e p re p a id . o r b y F ed e ra l E xp re s s o r a n equ iv a le n t overnight d el iv er y s er vi ce .a dd re ss ed t o t he - p ar ti es at:

If to Astrazeneca, to : I f to In stitu tio n. to : T ec hn ic al

A d d re s s : 1800 C on co rd P ik eW i lm in g t o n , DE 19850-5438Facsimile: 3\.J2,,!)~6-2730

Atten t ion : Simi K. Saini, E~

A dd re ss : D ep t o f P sy ch ia try2450 R iv ers id e A ve nu eM in n e ap o lis . M N 55455

F a c sim i le : 6 1 2- 62 7 -4 8 08Auenrion: Dr, S te ph en O lso n

W i t h a copy to : Adm in i s t r a t i v e :Ad d r e s s : I R O O C on co rd P ik e

W ilm in gto n, D E 198505438Fa cs im ile : 302886-157 8A tte n tio n : G en e ra l C ou n se l

A dd re s s : O ff ic e o f S po n so re d P ro je c ts A dm in .U n iv ers ity o f M i nn es ota430 U niv ers ity G ate w ay200 O ak S tre e t S EM i nn ea po lis , M N 5 54 55 2 07 0

29. Su rv iva l . The re sp e c tiv e r ig h ts a n d o b lig a tio n s o f th e p a r tie s se t fo r th in S e c tio n s 7 ,J I , 13-21. 23 , 28an d th is S ec tio n 29 sh a ll in d ef in ite ly su rv iv e th e exp ira tio n o r te rm in a tio n o f th is A gre em en t to th e exte n t n e c e ssa ryII I p re se rv e ~ uc h r ig hts a nd o blig atio ns .

30 , E ntire A gT ee me nt This A gre em en t, to ge th er w ith th e E xh ib its h ere to , c on stitu te s th e e ntire a gre em en tam on g th e p a r tie s h e re to w ith re sp e c t to th e su b je c t m atte r h e re o f a n d a ll p r io r a g re em en ts w ith re sp e c t th e re to a resu p e rse d ed h e re b y . N o am en dm en t o r m od if ic a tio n s h e re o f sh a ll b e b in d in g u n le s s in w ritin g an d d u ly exe cu te d b yau th o riz e d re p re se n ta tiv es o f e a ch p a r ty . N o w aiv e r o f a n y te rm o r co n d itio n o f th is A gre em en t sh a ll b e e ffe c tiv e 'u nle ss se t fo rth ill wr i t i n g by th e parry w aiv in g su ch te rm o r co n d itio n : In th e even t o f a n y inco n s is te~ cy b e tw eenth is A g_re em em an d the P ro to co l. th e te rm o f th is A g re em en t sh a ll p re v a il , '

3 '1 . C uu n te rp a r ts . T his A gre em en t m ay be exe cu te d in o n e o r m ore co u n te rp a r t c o p ie s , e a ch o f w hic h sh a llb e d e em ed an o r ig in a l a n d a ll o f w hic h sh a ll to g e th e r b e d e em ed to c on stitu te o ne a gre em e nt.

9UM SPA 0084


13/61

q

IN W 1T hTS S W HER EO F, th e pan ic s h ere to , ea ch by a d ul y a ut ho ri ze d rep re s en ta t ive , h av e execu ted th i sC lin ic a l S tu dy A gre em en t a s o f rhe d a le las t w ritte n be low ,

ASTRAZENECA P"~~S ~pBY:-U ~ '. .Name: W I ll IA M F . C O ! . . W J t , P Wl ) I R E C T O R , S O U R C l H QTitle:

lJN )V F,~ .E ::P "~It~N E SO T ABy: ~;>N am e : Kevin HcKoskey Name: S t e ph e n Olson. MDTi t le : Grants Manager Ti t le : P ri nc ip a l I nv e st ig a to r

Date:._~-- ,-13__,_{o_ '2 .. ~Dat.e:_?!15/02 ..

10UM SPA 0085


14/61

Exhibit A'STUDY BUDGET, P AYMEN T SCHEDULE A ND PROCEDURES

PR O TOCO L NO : S077IUOl14 I N ST I TUT ION : University o f MinnesotaP RIN C IP AL IN V ES TIG A TO R : Stephen Olson, M.D.P A T 1EN T ENR OL L lv 1EN T CLO SIN G D AT E : A u gu st 2 00 3D A TA COM PLE T rO N D A T E : S ep tem b e r 2004M I N IMUM ENROU l v l ENT : 2 0 S u b je c tsM AXIM UM EN RO L LM EN T : 30 S u b je c ts

BREAKDOWN OF PA ThiENTS

I. IN IT IAL P A YMENT $16 ,3 62U pon rec e ip t a n d app ro v a l o f a ll re g u la to ry d o cum en ts a n d th is s ig n ed C lin ic a l S t udy Ag r e emen t , Asrrazeneca sha l lfo rw ard a p aym en t o f $16 ,3 62 to th e re p re se n ta tiv e n o te d b e low , T h is In itia l P aym en t is a re fu n d ab le , a d v an c ep aym en t fo r th e f irs t p a tie n t e n ro lle d an d wi l l b e d ed u c te d from fu tu re P er S ub je c t P aym en ts , If In stitu tio n d oe s n oten ro l l at l eas t ISubject in to th e S tu d y w ith in 8 w eek s o f th e d a te o f its re c e ip t o f the S ru dy D r~ g, th is A gre em en t.m ay he im m ed ia te ly te rm in a te d b y A stra 'Z en e c a , an d In s titu tio n sh a ll re fu n d to A !;traZ en ec a th e $ 16,362 In itia lP a ym e n t

II P ER S UBJE CT P A Y I>ff iN T $J6,362Per S ub je c t P aym en ts sh a ll b e m ad e fOT evaluable, e lig ib le S ub je cts o nly , An e li gi bl e S u bj ec t is om: w ho m ee ts th ein c lu s io n /exc lu s io n requ irem en ts o f th e P ro to co l, w ho w as en ro lle d b y In s titu tio n an d fm m w hom I nfo rm ed C on sen th as b ee n o bta in ed , 'A n e va lu ab le Subject is o ne fO T w hom a ll C RFs h av e b e en com ple te d in a c co rd an c e wi t h th eP ro to co l, a n d w ho h a s com ple te d th e ap p ro p r ia te s tu d y p ro ced u re s a s se t fo r th ill th e P ro to co l, a n d u n d e rg o n e th eev a lu a tio n s requ ire d b y th e P ro to co l fo r a s se s sm en t o f e ff ic a cy an d sa fe ty , T he p e r su b je c t c o s t in c lu d e s su b je c tre la te d co s ts a s w ell a s n o n -sub je c t c o s ts su ch a s o v e rh e ad exp en se s , E CG p rep ara tio n & 're v iew , la b o ra to rys pe ci m en p re pa ra ti on & a na ly sis , b lo od p re ssu re m on ito rin g, p sy ch ia tr ic ra tin gs , c om p le tio n o f c ase re po rt fo rm s.a dm in is tra tiv e c os ts , c os ts fo r s ub je ct travel, e tc ., a n d equ ipm en t c o s ts .. P e r S u b jec t P aym en ts sh a ll b e com e d u e fo re ac h e va lu ab le , e lig ib le S ub je ct u po n Astrazcncca's sa tis fa cto ry re vie w o f a ll S tu dy D oc um en ta tio n, in clu din gcom ple te d C RFs an d c lo se-o u t a u d its .. N o p aym en ts wi l l b e m ad e fo r S u b je c ts w ith u n sa tis fa c to ry C RFs o ru n re so lv ed d am d e fic ie n c ie s in th e Study D ocum en ta tio n . A com ple te d C RF is o n e th a t is s ig n ed b y P rin c ip a lIn v e s tig a to r w hen requ ire d an d co n ta in s a il c om ple te v e r if ie d in fo rm atio n in a c co rd an c e w ith th e p ro c ed u re s a n dsch ed u le d a sse s sm en ts a s s ta te d in th e P ro to co l 'In a d d itio n to th e P er S ub je c t P aym en t" A stra 'Z en e c a w ill p ay "b ed " co s ts fo r in d iv id u a l p a tie n ts u p 10 $400 p e r d ayfo r up to 3 d ay s .A srm 'Z en ec a w ill p ay fo r re aso na ble ERB fe e s up o n rev iew an d re c e ip t o f inv o ic e to :

Q ui nt il es , I nc ,A t tn : P a ym e n ts10201 W a te rid ge C irc leS an D ieg o , C A 92 J 2 J

C lin ic al ra te rs a t th e In s t itu t ion a re re qu ire d to c om p le te th e in itia l tra in in g/c er tif ic atio n in O J d c r to p a r tic ip a te in th es tu d y . A straZ en e c a w ill n o ; p ay fo r th is in itia l tra in in g . A straZ en e c a wi l l p ay $ 25 0 fo r e ac h o f th e re -c er tif ic atio ntra in in g sc ~s io ns th at ~ re re qu ire d nOI to exc e ed 8 se ss io n s fo r e a ch s ite .

11

UM SPA 0086


15/61

As t r~neca sh i l l p a y 10 In sti tu tio n th e P er S ub jec t P ay me nts ac co rd in g to th e m ile s to ne p ay m e n ts s et fo rth b elo w :Comp l e t i o n o f V is i t .3:C om ple tio n o f V is i t 6:C om ple tio n o f V is i t 9:C om p le tio n o fV is i! 12:C o m ple tio n o rV is it 15:C om ple tio n o f V is i t 19:U p on S atis fa cto ry c om p le tio nand v alid a tio n o f a ll C RFsf or t he p at ie nt:

$3,462$1 ,432$2,352$2,JJ6$1.890$3.336

$1,704,A s!r nZ en ec a w ill a ls o pa y $ 1()() to In sti tu tio n fo r P sy ch o-E du ca tio na l In te rv en tio ns th at a re c om ple ted fo r v is its 1. 3,5, 8, an d J 0 fo r e ac h p at ie nt,C om pe nsa tio n fo r subjects who do no t com ple te th e S tu d y w ill b e calculated on a prorated basis according to th efollowing s ch ed ule [p art ia l v is its w ill n ot b e p aid ]:

C om ple tio n o f V is i t 1:C om ple tio n o f V is it 2:C om ple tio n o f V is it 3 :C om ple tio n o f V is i t 4 :C om ple tio n o f V is i t 5:C om ple tio n o f V is i t 6:C om ple tio n o f V is it 7:C om ple tio n o f V is it 8:C om ple tio n o f V is i t 9:C om ple tio n o f V is i t 10:Completion of Vis i t 11:Comp l e t i o n of Visit 12:

$2 ,568$3,138$3,462$4,092$4 ,374$4,944$5,.574$6,J44$7 ,296$7 ,926$8,556$9,432

C om ple tio n o f V is i t 13:C om ple tio n o fV is i! 14 :C om ple tio n o f V is it 15 :C om ple tio n o f V is it 16 :C om ple tio n o f V is i t 17 :C om ple tio n-o f V is i t 18:C om ple tio n o f V is it 19:C om ple tio n o f V is it 20:C o m p le ti on o fV is i! 21:C om ple tio n o f V is i t 22:C om ple tio n o f V is i t 23:

$10,062$10,692$11 ,322$11,952$12.582$13 ,212$14 ,658$14 ,820$15 ,270$1. '5.432$16,362

S ub je cts w ho d id n ot fu lfi ll th e qu alif ic a tio ns c ri te ria a nd w ere co ntin ued in to the S t udy will on ly h e c om pen sa ted fo ru p to th e p oin t o f ra nd om iz atio n.

A straZ en eca w ill p ro v id e re im bu rs em en t fo r a m axim um o f 7 s c reen fa ilu re s a t $600 p er p a tien t to in c lu de a lli nv oi ce d c os ts .E n r o l l rn en t o f m ore th an 30 e l ig ib le . p atie nts a nd p ay m en t o f m ore than 7 s cr ee n f ai lu r es wi l l be p er m itte d u po nap pro va l b y A straZ en eca a nd p rio r am en dm en t o f T his c on tra ct. In th is c ase , th e In ves tig ato r/ln st i tu tio n sh ou ldcon tac t Asrrazeneca to a m e n d t h is c o n tr a ct .Qua r te rly P er S ub jec t P aym en ts w ill b e m ad e th ro u ghou t th e te rm o f th e S tu dy .All p ay men ts re qu ired h ereund er sh a ll b e m ade p ay ab le to Regents of the University of Minne s o t a , Tax I D. N o .41 -60 07 .5 13, a nd m a ile d to :

R eg en ts o f th e U niv ers i ty o f M in ne so ta('_lo O ffice o f S po nso red Fin an cia l R ep on in g200 O ak S L S ESui t e450M in neap olis , M N 55455-2070A ttn : Jo an D o na ld so n

12UM SPA 0087


16/61

In Page 2 of4

Thanks for sending that info on to me&llook forward to the details.Regarding the proposed thank you gift.,Tina Olexy at AZ has agreed toreimburse your site for the full $400 cost of the booth, As we discussed,please create and submit an invoice for this amount to Maria Karvois, andshe will have it processed for payment.

As for the CAFE brochures, M&Ms, pens and Post It Notes, I m glad that youwere able to track those down, even if it was a wild goose chase. J

Please let me know if you have any questions.

Thanks!Jody

-----Original Message-----From: Jeannie Kenney mailto:[email protected]]Sent: Monday, September 15, 2003 11:57 AMTo: Jody Robertson; [email protected]: Elizabeth LemkeSubject: RE: Jody's address

Jody and Jen,Thanks for the address. I'm glad I checked. It's not close to the one Ithought it might be. Jody, I'm finally sending you the program for theMental Health Conference we're attending next week.Elizabeth and I made an executive decision about what we would like as aThank You for the recruitment presentation. To offset the cost of ourbooth and to buy chocolates to attract folks to us we'd like to ask for amonetary gift. Not knowing exactly what is reasonable we are throwing out$200.00. Our booth costs about $400 and we spent about $80.00 on candylast year.Any idea when we might receive the brochures and other CAFE items (pens,post-it's, etc.)? We did receive our sweatshirts today. Thanks so much.They are really nice.Thanks for your support with this. We hope it brings a lot of referrals. UM CAFE 0565

Pr in ted for Jeannie Kenney -";[7

9118/03
mailto:[email protected]:[email protected]


17/61

[email protected]. 02:05 PM 7111103-0500, Re: CAFE-Amendment 2 approvals

To: [email protected]: Jeannie Kenney Subject: Re: CAFE-Amendment 2 approvals!revised ICFsCc:Sec:Attached: J:\Olson's trials\CAFE\Consent Forms\Adolecent Assent\ADOLESCENT 03-25-03.doc; J:\Olson's trials\CAFE\Consent Forms\Adult Consent\adult 3-2S-03.doc; J:\Olson'strials\CAFE\Consent Forms\Parental Consent\parental 03-25-03.doc;

Hi Amy,Attached you'll find the most recent ICFs. The IRS really got mixed up with approving theprotocol change and so it wasn't until actually just this last week that we rec'd final approval.They approved the consents before approving the protocol. I now need to go back and haveeveryone else sign new consents so they are officially informed of the protocol change. I'll befaxing the IRS approval letters asap. If you have questions, let me know.JeannieAt 12:29 PM 7/11 /03 -0500, you wrote:Hi- .Can you please fax a copy of your amendment 2 approvals and revised ICFsThey need to have these in the central file!Thanks-Amyfax- 513-731-2159

****************1 MPORTANT--PLEASE READ*******************This electronic message, including its attachments, is COMPANY CONFIDENTIALand may contain PROPRIETARY or LEGALLY PRIVILEGED information. If you arenot the intended recipient, you are hereby notified that any use, disclosure,copying, or distribution of this message or any of the information includedin it is unauthorized and strictly prohibited. If you have received thisme ss ag e in e rr or . p le as e imme dia te ly n otify th e s en de r b y r ep ly e -ma i! a ndpermanently delete this message and its attachments, along with any copiesthereof. If this electronic message contains a zipped attachment and you donot have a decompression tool, you may download unZIP (free of cost) fromhttpJ/www.mk-net-work.com/us/uz/unzip.htm. Alternatively, you may requestthat the attachment be resent in an uncompressed format. Thank you.************************************************************************

1Printed for Jeannie Kenney

UM CAFE 0582
mailto:[email protected]:[email protected]://httpj/www.mk-net-work.com/us/uz/unzip.htm.http://httpj/www.mk-net-work.com/us/uz/unzip.htm.mailto:[email protected]:[email protected].


18/61

jennifer.Lfrantz@quintiles ..com. 10:04 PM 6/4/03 -0400, RE: Request for funds Page 1 of.5

X-From_: [email protected] Wed Jun 421:12:422003X-Umn-Remote-Mta: [N] mhub-w5.tc ..umn.edu #+LO+NMX-Umn-Remote-Mta: [N] maiI2,quinti les.com #+NE (1,-)X -Umn-Report-As-Spam: httQ_J/umn.J!du/mc/s 7BMnciOkQgTA$7 AelwZbbhgK21 d4KoFBYH3nr9sHhRNwSubject RE: Request for fundsTo: Jeannie Kenney From: jenn [email protected]: Wed, 4 Jun 2003 2204:21 -0400X-MIMETrack: Serialize by Router on ONEWLN01/QNEW/Quintiles(Release 5..0.5[September 22, 2000) at06/04/2003 10:04:54 PM,Itemize by SMTP Server on QRTPLC02/QRTP/Quintiles(Release 5.0,11 [July 24,2002) at06/04/200310:12:22 PM,MIME-CD by Router on ORTPLC02/QRTP/Quintiles(Release 5.0.11 [July 24, 2002) at06/04/2003 10:12:22 PM,

MIME-CD complete at 06/04/2003 10: 12:22. PM,Serialize by Router on QRTPLC02/QRTP/Quintiles(Release 5,0.11 [July 24, 2002) at06/04/2003 10:12:36 PM

Hi Jeannie,This is no problem, AZ has given the okay for this pt and the associatedtransportation costs, This is the template I made up for another site .'they were tracking mileage, you can edit it to describe car service.Please include the visit number and round-trip cost

Depending on the mileage it would be between $30 - $50 One of ourstudies is using this service. It was more cost efficient than cab fareand it's more comfortable as the clients are picked up in pretty nicevehicles. Kind of makes them feel important

(See attached file: mileage reimbursement template ..xls)Thanks,Jen

Jeannie Kenney on 06/04/2003 11:59:28To: [email protected]:Subject RE: Request for funds

Jeannie

At 11:44 AM 6/4/03 -0400, you wrote: UM CAFE 0594P rin te d fo r Je an nie K en ne y < ke nn e097@ um n .e du > 6/5/03 8
mailto:[email protected]:[email protected]:[email protected]:[email protected]:[email protected]:[email protected]


19/61

UN IVER SITY O F M INN ESO TAAmbulatory Research Center Deportment of Psychiatry

Medical SchoolRiverside Professional Building606-24117Avellue SowhSuite 602Minneapol is. MN 55454

April 25, 2003

Quintiles, Inc.Mary Ann O'Herron10201 Wateridge CircleSan Diego, CA 92121Dear Mary Ann,

Please find enclosed a receipt for refreshments, Our CAFE team presented informationabout the study at a private psychiatric outpatient clinic in the area. I t was nice to providethis to them as a way to acknowledge the time and attention they gave us over their lunchhOUL Thank you for processing this request. 111es taff person who purchased the foodfor this function is Elizabeth Lemke .. If you have further questions, please feel free tocontact me at (612) 627-4363.Sincerely, f > ',.~\ .., ~" ..- ~--...,.;' .' i'\ ;YC:;' r./}/J / 7 ) , . ,;('FI./l-n_tA ..~1([~nM. Kenney, LICSW .~CAFE Study Coordinator (.Ene.

UM CAFE 0610


20/61

M:::nicaPallett, 11:21 AM 4/15/04 -040...: [cafesc] CAFE PANSS Rater Certification Statu Page 10f3

X-From_: [email protected] Thu Apr 15 10:22:132004X-Umn-Remote-Mta: [NJ mhub-m6.tc.umn.edu [160.94.23.36] #+LO+NMX-Umn-Remote-Mta: [N] zebulon.med.unc.edu [152.19.4.47] #+NR+UF+CU (A,-)X-Urnn-Repcrt-As-Sparn:


21/61

M( nica Pallett, 11:21 AM 4/15/04 -040 ... : [cafesc] CAFE PANSS Rater Certification Statu Page 2 of3

-----Original Message-----From: Jeannie Kenney [[[l.fl_ili;Q;ke[Ul~Q~Z@!J_rn[h


22/61

Monica Pallett, 11:21 AM 4115/04 -040....: [cafesc] CAFE PANSS Rater Certification Statu Page 3 of 3

At 11:06 AM 3/10/04 -0500, you wrote:Hello everyone,Please see the attached list ofPANSS raters, by site, who are not currently certified for thePANSS. Also listed are the items that are outstanding. Please see that all raters complete thePANSS on-line certification as soon as possible. Feel free to contact Ismail Abdelkhalek( g ! j I! Y ' . .: .~ ~ @ e l 'D g J L . ! : lD C ; . : ~ g . ! :l .) if you have any difficulties with the CAFE website.Thank you,Jody RobertsonDepartment of PsychiatryUniversity of North Carol ina at Chapel Hillphone 919843.3420fax 919 843.7859pager ..919.216.0898

You are currently subscribed to cafesc as: kenne097@)lmn.eduTo unsubscribe send a blank email to leave-cafesc-1433002N@listserv ..unc.edu

UM CAFE 0668Printed for Jeannie Kenney 4115/04


23/61

UN< tS CHOO L O F M ED IC IN EDEPARTMENT OFPSYCHIATRY

MEMORANDUM

TO : CAFE Investigators and StaffFROM: Jeffrey LiebermanDATE : December is", 2003RE : CAFE Enrollment Kickoff

Dear Colleagues,We have now worked together on the CAFE project for almost two years. Our common goal is to completethe study successfully and provide data that will answer critical questions about the use of atypicalantipsychotic drugs in patients in their first psychotic episode. I thank you for your superb efforts in makingthis trial possible and successful to date. Although recruitment has recently gone quite well, we still mustconsider the risk for not meeting our target of 400 subjects. As of Sunday, November 30th, 2003, we haveenrolled 328 subjects out of our target 400. There are only 13 weeks left to enroll subjects and there is nopossibility of further extending the enrollment period. We have been averaging 20 new subjects a month forthe past 6 months now but we need to enroll about 25 per month for the remainder of the trial. If each sitecan enroll 1 patient per month in the remaining 3 months then we will meet our goal. I encourage you tomake every effort to enter patients into CAFE in this final stage of enrollment With a little extra effort, wewill succeed.Best Wishes to All for a Happy Holiday and Healthy New Year,Jeffrey Lieberman

The Univers ity of North Carolina ,,1 Chapel Hill, Campus Box # 7J 60, Chapel Hill, North Carolina 27599-7 J 60Telephone; (9J9) 966-8990; FAX: (9J9) 966-8994; E-MAIL:jliebernUlIl@lll1udu

UM CAFE 0677


24/61

In Page 2 of4

Thanks for sending that info on to me&llook forward to the details.Regarding the proposed thank you gift, Tina Olexy at AZ. has agreed toreimburse your site for the full $400 cost of the booth. As we discussed,please create and submit an invoice for this amount to Maria Karvois, andshe will have it processed for payment.

As for the CAFE brochures, M&Ms, pens and Post It Notes, I m glad that youwere able to track those down, even if it was a wild goose chase. J

Please let me know if you have any questions.

Thanks!Jody

----Original Message-----From: Jeannie Kenney mailto:[email protected]]Sent: Monday, September 15,200311:57 AMTo: Jody Robertson; [email protected]: Elizabeth LemkeSubject R E : Jody's address

Jody and Jen,Thanks for the address. I'm glad I checked. It's not close to the one Ithought it might be. Jody, I'm finally sending you the program for theMental Health Conference we're attending next week.Elizabeth and I made an executive decision about what we would like as aThank You for the recruitment presentation. To offset the cost of ourbooth and to buy chocolates to attract folks to us we'd like to ask for amonetary gift. Not knowing exactly what is reasonable we are throwing out$200.00. Our booth costs about $400 and we spent about $80.00 on candylast year.Any idea when we might receive the brochures and other CAFE items (pens,post-it's, etc.)? We did receive our sweatshirts today. Thanks so much.They are really nice.Thanks for your support with this. We hope it brings a lot of referrals. UM CAFE 0565

Printed for Jeannie Kenney ~J7

9118/03


25/61

[email protected]. 02:05 PM 7/11/03 -0500, Re: CAFE-Amendment 2 approvals

T o : Amy .VandenEynden@qu in t i l es .comF r om : J e an n ie K en n ey < k en n e0 9 7@umn. ed u >S u bje ct: R e : C A F E - Ame ndme nt 2 a pp ro va ls /re vis ed IC F sC c:B e e :A t ta ch ed : J :\O ls on 's tr ia ls \C A F E \ C on se nt F o rm s\A d o le ce nt A s se nt\A D O L E S C E N T 0 3-2 5-0 3 .d o c; J :\O l s on 's t ri als \C A FE \ C o n s e nt F o rm s\A d u lt C o n s e n t\a d u lt 3 -2 . 5- 03. .d o c ; J : \O ls on 'st ri als \C A FE \ C o n s e nt F o rm s\P a r e n ta l C o n s e n t\p a re n ta l 0 3 -2 5 -0 3 .d o c;

H i Am y,A tta ch ed yo u'll f in d th e m os t re ce nt IC F s. T he IR B re ally g ot m ix ed u p w ith a pp ro vin g th ep ro to co l c ha ng e a nd s o it w a sn 't u ntil a ctu ally ju st th is la st w e ek th at w e re c'd fin al a pp ro va l.T he y a pp ro ve d th e co ns en ts be fo re a pp ro vin g th e p ro to co l. I n ow n ee d to g o ba ck a nd h av ee ve ryo ne e ls e s ig n n ew c on se nts s o th ey a re o ff ic ia lly in fo rm ed o f th e p ro to co l c ha ng e. I ' ll befa xin g th e IR B a pp ro va l le tte rs a sa p. I f yo u h av e q ue stio ns , le t m e k no w.Jeann ieA t 1 2:2 9 P M 7/1 1/0 3 -0 50 0, yo u w ro te :H i- .C an yo u p le ase fa x a cop y o f you r am en dm en t 2 a pp ro va ls an d re vised IC FT he y n ee d to h av e th es e in th e ce ntra l fi le !T hanks -A myf a x - 513 -731 -2159

* ** ** ** ** ** ** ** *1 M PO RT AN T - -PL EA SE RE AD * ** ** ** ** ** ** ** ** **T h is e le ctro nic m es sa ge , in clu din g its a tta chme nts , is C O M P A N Y CO N F I D E N T I A Lan d m ay con ta in P R O P R IE T A R Y or L E G A LL Y P R IV IL E G E D in fo rm atio n. If you a ren o t t he in te n de d r ec ip ie n t, y ou a re h e re by n o tif ie d th a t a n y u s e, d is clo s ur e,c op yin g , o r d is tr ib utio n o f th is m e ss a ge o r a n y o f th e in fo rm a tio n in clu d edin it is u na uth orize d a nd s tr ic tly p ro hibite d. If yo u h av e re ce iv ed th ism es sa ge in e rro r, p le as e imme dia te ly n otify th e s en de r by re ply e -m ail a ndp erm an en tly d ele te th is m es sa ge a nd its a tta chme nts , a lo ng w ith a ny c op ie sth ere of. I f t h is e le ctro nic m es sa ge c on ta in s a zip pe d a tta chme nt a nd yo u d on ot h av e a d eco mp re ss io n to ol, yo u m ay d ow nlo ad u nZIP (fre e o f co st) fro m:h t tp :/ /www.mk-ne t -wo rk .com/us /uz /unziR .h tm . A l te rn a tiv e ly , y ou m a y r eq ue s tth a t the a tta chmen t be re sen t in an uncompressed fo rma t. T hank you .*********~**************************************************************

Printed for Jeannie Kenney 1

UM CAFE 0582
mailto:[email protected]:[email protected]://www.mk-net-work.com/us/uz/unziR.htm.http://www.mk-net-work.com/us/uz/unziR.htm.mailto:[email protected]:[email protected].


26/61

[email protected]. 10:04 PM 6 /4103 -0400, RE: Request for funds Page 1 of5

X-From_:[email protected] Jun 421:12:422003X-Umn-Remote-Mta: [N ] mhub-wS.tc.umn.edu #+LO+NMX-Umn-Remote-Mta: [N] maiI2.quintiles.com #+NE (1,-)X-Umn-Report-As-Spam: http:/ /umn.edu/mc/s{BMnciQkQgTA$7 AelwZbbhgK2,1 d4KoFBY H3nr9sHhRNwSubject RE: Request for fundsTo: Jeannie Kenney From: jennifer.Lfrantz@quintiles ..comDate: Wed, 4 Jun 2003 22:04:21-0400X-MIMETrack: Serialize by Router on QNEWLN01/QNEW/Quintiles(Release 5.0.5[September 22, 2000} at06 /04 /2003 10:04:54 PM,Itemize by SMTP Server on QRTPLC02/QRTP/Quintiles(Release 5.0.11 [July 24,2002} at06 /04 /200310:12:22 PM,MIME-CD by Router on QRTPLC02/QRTP/Quintiles(Release 5.0.11 [July 24,2002) at06 /04 /2003 10:12:22 PM,MIME~CD complete at 06 /04 /2003 10:12:22 PM, /Serialize by Router on QRTPLC02/QRTP/Quintiles(Release 5.0.11 [July 24, 2002) at06 /04 /2003 10: 12:36 PM

..Hi Jeannie,This is no problem, AZ has given the okay for this pt and the associatedtransportation costs. This 'is the template I made up for another site.they were tracking mileage, you can edit it to describe car service.Please include the visit number and round-trip cost(See attached file: mileage reimbursement template. xis)Thanks,Jen

Depending on the mileage it would be between $30 - $50 One of ourstudies is using this service. It was more cost efficient than cab fareand it's more comfortable as the clients are picked up in pretty nicevehicles. Kind of makes them feel important.

Jeannie Kenney on 06 /04 /2003 11:59:.28To: jennifer.l.frantz@quintiles comcc:Subject: RE: Request for funds

Jeannie

At 11:44 AM 6/4/03 -0400, you wrote: UM CAFE 0594Printed for Jeannie Kenney 6/5/03 8
mailto:[email protected]:X-From_:[email protected]:jennifer.l.frantz@quintilesmailto:jennifer.l.frantz@quintilesmailto:X-From_:[email protected]:[email protected].


27/61

U NIV ER SITY O F M IN NESO TAAmbulatory Research Center Department of Psychiatry

Medical SchoolRiverside Professional Building606-24ch Avenue SouthSuite 602Minneapolis, MN 55454

April 25, 2003

Quintiles, Inc.Mary AIm O'Herron10201 Wateridge CircleSan Diego, CA 92121Dear Mary Ann,Please find enclosed a receipt for refreshments. Our CAFE team presented informationabout the study at a private psychiatric outpatient clinic in the area. It was nice to providethis to them as a way to acknowledge the time and attention they gave us over their lunchhour. Thank you for processing this request. The staff person who purchased the foodfor this function is Elizabeth Lemke. If you have further questions, please feel free tocontact me at (612) 627-4363.Sincerely, f~ ',.....\., ,.".> -... -1 .?\ ;!rte3:./)/} I7 ) , . , ; f>;1, '1-/]/\...(:"


28/61

M:cn.icaPallett, 11:21 AM 4/15/04 -040 ...: [cafesc] CAFE PANSS Rater Certification Statu Page 10f3

X-From_: [email protected] Thu Apr 1510:22:132004X-Umn-Remote-Mta: [N ] mhub-m6.tc.umn.edu [160.94.23.36] #+LO+NMX-Umn-Remote-Mta: [N] zebulon.med.unc.edu [152.19.4.47] #+NR+UF+CU (A,-)X-Umn-Report-As-Spam:


29/61

M. nica Pallett, 11 : 21 AM 4115/04 -040 ... : [cafesc] CAFE PANSS Rater Certification Statu Page 2 of 3

----Original Message-----From: Jeannie Kenney [W1!ilto:keO_lJ.e02.Z@lLl'!lQ.,,{;Qy]Sent: Friday, April 09, 2004 11:34 AMTo: Monica PallettSubject: Re: FIN: [cafesc] CAFEPANSSRater Certification Status

Dr. Olson was certified to rate PANSS at the Investigator's meeting.JeannieAt 10 : 11 AM 3/30104 -0500, you wrote:

Hi Jeannie,

Dr Olson has not viewed the Jose tape and still needs.to do so for CATIE However, he has neverbecome certified as a PANSS rater for CAFE and therefore should NOT be rating the PANSS forCAFE. If he is doing so, or plans to do so, he needs to go on the CAFE website and score those threetapes ASAP (fax one page score sheet to me at 9198437367)

Thanks,

Monica

-----Original Message-----From: Jody Robertson [mgu.tQ;)_QctL8QP_~~Q[l@m_E;_Q-,-lJ_rlc.edu]Sent: Thursday, March 25, 2004 10:18 AMTo: 'MoniCa Riedy Pallett'Subject: FW: [cafesc] CAFE PANSSRater Certification Status

Does he?

-----Original Message-----From: Jeannie Kenney [mSl.UtQ.Js;.!:l_n_;991@~_rn.n.g9y]Sent: Tuesday, March 16, 2004 5:05 PMTo: Jody RobertsonSubject: Re: [cafesc] CAFEPANSSRater Certification StatusHi lody,I don't believe Dr. Olson ever did lose. He still needs to do the recert doesn't he?Jeannie

UM CAFE 0667Printed for Jeannie Kenney 4115104


30/61


31/61

UNc tS CHOO L O F M ED IC IN EDEPARTMENT OF

PSYCHIATRY

MEMORANDUM

TO: CAFE Investigators and StaffFROM: Jeffrey LiebermanDATE: December is", 2003RE: CAFE Enrollment Kickoff

Dear Colleagues,We have now worked together onthe CAFE project for almost two years. Our common goal is to completethe study successfully and provide data that will answer critical questions about the use of atypicalantipsychotic drugs in patients in their first psychotic episode. I thank you for your superb efforts in makingthis trial possible and successful to date. Although recruitment has recently gone quite well, we still mustconsider the risk for not meeting our target of 400 subjects. As of Sunday, November 30th , 2003, we haveenrolled 328 subjects out of our target 400. There are only 13weeks left to enroll subjects and there is nopossibility of further extending the enrollment period. We have been averaging 20 new subjects a month forthe past 6 months now but we need to enroll about 25 per month forthe remainder of the trial. If each sitecan enroll 1 patient per month in the remaining 3 months then we will meet our goal. I encourage you tomake every effort to enter patients into CAFE in this final stage of enrollment. With a little extra effort, wewill succeed.Best Wishes to All for a Happy Holiday and Healthy New Year,Jeffrey Lieberman

The University of North Carolina 1 11 Chapel Hill, Campus Box # 7160, Chapel Hill, North Carolitta 27599-7160Telephone: (919) 966-8990; FAX: (919) 966-8994; E-MAIL: [email protected]

UM CAFE 0677


32/61

UN IVERS ITY OF IvfIN N E SO T AT w il l C it Ie s Campus Rcsc arch Subjects.' Proicction Progroms

lnsiitutiono! ""'l'II'\\' Board: Human Sul.jcct Cnmmiur, IIRB;lnstuu uonal Animal Care and esc COflllT1i'I;~~e I f .ACCCj

Mavo M"iI Code 820[)528 Mayo Memorial Building4 20 D et a 'o re Street S. Mmne apous, MN 554556[26265654Far 6126Z6606Jirh@umfl cdu/[email protected]/IWH.'II'I cs earch, llIfm ..cdJi.!subjects. hun

A ugu s t 06, 2002T imo t hy W, Ol senOph t h a lmo l o gyBox 493 Ma y oM inn e ap o lis C am pu s

R e : "/\11 E va lu a tio n o f E ffica cy and S a fe ty o f P o s te r io r J uxta sc le ra l In je c tio n s o f AnecortaveAce t a t e 15 m g (O .Sm l o f .30 mg/rnl A neco r ta v e A ce ta te S te r ile S u sp en tio n ) V ersu sV I SUQ1 'NE in P atien t w ith Sub fove a l E xud a tiv e A ge -R ela te d M acu la r D eg en a ra tio n

\ (/\M D ) E lig ib le fo r In itia l T re a tm en t w ith P h o to dy n am ic T he ra py '(PD T ) U sin gV I SUDYN ' E "H um an S ub je c ts C o d e N um b er : 02061\126801

This correspondence replaces my letter dated August OJ, 2002.De a r Dr. Ol sen :At i ts m ee t in g on Ju ly 31,2002 th e IRB: H um an S u b je c ts C om m itte e reviewed your re sp on se to itsd e fe rra l a n d ap p rov ed th e re fe re n ced s tu dy (p ro to co l d a te d May 3,2002) .. F or g ra nt c er tific atio npu r po s e s you w ill n e ed th a t d a te a nd th e A ssu ra n c e o f C om p lia n c e n um be r w h ic h isFW A00000312 (Fa irv iew H ea lth S y s tem s R e se a rch FWAOOOO(325 ) . A pp rov a l fo r th e s tu dy w ille xp ire o n e y e a r from th a t d a te . A rep or t fo rm wil] b e sen t tw o m on th s b e fo re th e exp ira tio n d a te ,I f y o u w o u ld lik e u s to s en d c e r tifica tio n o f ap p ro v a l to a f und ing agency, p le as e p ro v id e th e n am eand ad d re ss o f y ou r c on ta c t p e rso n a t th e ag en cy .T h e co d e num b er abo v e is a ss ig n ed to y ou r re se a rch . T h a t n um b e r an d th e title o f yo u r s tu dyshou ld beused in a ll c om m un ica tio n w ith th e IRE o ff ic e , 'IR E app ro v a l o f t h is s tu d y in c lu d e s th e con s en t fo rm d a te d 07112/2002 and re c ru itm en t m ate r ia lsrec e i v ed on Jun e 1 1 , 2002.T h e IR B no tes th a t th e u se o f d ru g s /b io lo g ic s /d ev ic e s in th is s tu d y is ca r r i ed o ut u n de r fN D i : 5 6 5 9 5an d ID S #2266R O .T h e IR B w ou ld I ik e to s t re ss th a t su b je c ts w h o go th ro ugh (h e con sen t p ro c e ss a re c on sid e re den ro lle d p a r tic ip a n ts a nd a re cou n te d tow ard th e to ta l n um b e r o f su b je c ts , e v en if th ey h av e n ofu rth e r p a rt ic ip a tio n . in th e s tu d y .. P le as e k e ep th is in m in d w hen c a lc u la tin g th e n um be r o f su b je c tsy o u requ e s t. T h is s tu d y is c u r re n tly ap p ro v ed [o r 200 sub jec ts . I f y ou d e s ire a n in c re as e in th enum b er o f a pp ro v ed sub jec ts , y o u w ill n e ed to m ak e 3 f 0 I111a l r equ e s t.

UM IRS 032
mailto:/[email protected]:/[email protected]


33/61

A s P rin cip al In ve stig ato r of this project, you art required by federal reg u la tio n s to in fo rm th e IR Bof any proposed changes in your research that \\ ill affect human subjects. Changes should not beinitiated u n ti l w r it te n lRB app ro v a l is received. Adverse events s hou l d be reported to the IRB asth ey o ccu r . R esea rc h p ro jec ts a re su b jec t to con tin u in g rev iew and renewal. I f y ou h av e anyquestions, please cal l the IRE office at (612) 626-5654On behalf of the JRB , I w ish you su ccess w ith you r research

~A~ jCa r o l Siegel, M&~ IP ' - 0A ss is ta nt D ire cto r C)CS/ki

CC: Sally C oo k, E ric Steuer

Uf\i \RB 0325


34/61

C om pa ra tiv e E ffe c tiv en ess o f A ntip sy ch otic M e dic a tio ns in P at ie nts w ith S ch izo ph ren ia

Consent AmendmentComparative Effectiveness of Antipsychotic Medications in Patients with Schizophrenia(The CATIE Study)Study Site: University of MinnesotaSponsor: National Institute of Mental Health

The U.S. Food and Drug Administration has issued a new warning about an increased risk ofhyperglycemia (high blood sugar) and diabetes mellitus in persons taking the antipsychotic drugsaripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone, alJ of which areused in the CA TIE trial. In some cases, hyperglycemia has resolved when the atypicalantipsychotic was discontinued; however, some patients still needed anti-diabetic treatment afterstopping the atypical antipsychotic drug. In rare cases hyperglycemia is associated withketoacidosis (high levels of acid in the blood), coma, and death.The new warning does not apply to the other CA TIE study drugs (perphenazine and fluphenazinedecanoate) but all persons with schizophrenia are thought to be at increased risk ofhyperglycemia and diabetes mellitus compared to the general population.In the CA TIE study we are monitoring your blood glucose quarterly with a fasting blood glucoseest and a test called Hemoglobin Al c, Symptoms of hyperglycemia include excessive thirst andlrinking, increased urination, increased appetite and eating, and weakness. If you develop any ofhese symptoms let your study doctor know as soon as possible. You will be asked to undergoasting blood glucose testing. Your doctor will then d

Documents

Schulz Exhibit 4