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PROTOCOL A5351025

eCRF COMPLETION GUIDELINES

Version 6, 28 SEP 2007

Revision History

The following table documents any updates made to the eCRF Completion Guidelines:

Version Number Version Date Amendment Details Author

1.0 29SEP2006 Final Version 1 A. HauptmannBaker (A. HB)

2.0 31OCT2006 Final Version 2 post IM updates A. HB

3.0 19FEB2007 Update Physical Exam section, Updated pages that need DONE populated, Include instructions on Screen Fail pages for S2 visit, PD substudy, medical history section, substudy pages for scan fails, if questionnaire question not answered insert Investigator Comment, missing date convention change/update, update PHQ and GAD completion.

A.HB

4.0 18MAY2007 Page numbering issue fixed, DXA CT update if scan unacceptable. Combination Con. Med. Update, Log pages marked as complete.

A. HB

5.0 28JUN2007 Addition of CNS Targeted Adverse Event Assessment page

Craig Ellery

6.0 17SEP2007 Added instructions to the Dosing Log page (Lost to Follow Up and ODIS reporting). Update to Subject Summary page. Added Investigator Declaration page instructions. Minor grammatical changes made.

Danelle Jones-Covington

Template Version: FINAL 01MAY2006 Pfizer Internal Use Page 1 of 41

Table of Contents

GENERAL GUIDELINES..................................................................................................................................... 4

Subject Data........................................................................................................................................................ 7

Header Information.............................................................................................................................................. 7

Demography:....................................................................................................................................................... 8

Menopausal STATUS:......................................................................................................................................... 9

Drug Allergies:..................................................................................................................................................... 9

Laboratory Samples (used for electronic laboratory data transmissions):.........................................................10

Vitals: ............................................................................................................................................................... 11

ECG: ............................................................................................................................................................... 12

Physical Examination:........................................................................................................................................ 13

Sub-Study Participation:.................................................................................................................................... 14

Medical History:................................................................................................................................................. 15

DXA SCAN:....................................................................................................................................................... 17

CT SCAN:......................................................................................................................................................... 17

All Questionnaires:............................................................................................................................................. 18

Three Factor Eating QUestionnaire (TFEQ)......................................................................................................18

Power of Food Scale (PFS):.............................................................................................................................. 18

Impact of Weight on Quality of Life (IWQOL-Lite):.............................................................................................18

Patient Health Questionnaire-9 (PHQ-9):...........................................................................................................18

Patient HeAlth QUESTIONNAIRE GENERALIZED Anxiety Disorder questionnaire – 7 (GAD-7):....................19

PHARMACOGENOMIC SAMPLE COLLECTION:.............................................................................................19

Pharmacodynamics:.......................................................................................................................................... 20

SMOKING Classification:................................................................................................................................... 20

Alcohol Classification:........................................................................................................................................ 21

Randomization:.................................................................................................................................................. 21

Dietician contact:................................................................................................................................................ 22

PHARMACOKINETIC Samples:........................................................................................................................ 22

DETAILS OF DOSING:...................................................................................................................................... 24

Subject Summary............................................................................................................................................... 25

Subject Summary (Screen Failure)....................................................................................................................25

Subject Summary............................................................................................................................................... 26

Week 1 FOLLOW-UP VISIT TELEPHONE CONTACT......................................................................................28

Dosing Log:........................................................................................................................................................ 29

Concomitant Treatment:.................................................................................................................................... 30

Non-Drug Treatment/Procedure:........................................................................................................................31

Adverse Events.................................................................................................................................................. 33

PFIZER DICTIONARY AND CODING SYSTEM................................................................................................37


CNS Targeted Adverse Event Assessment.......................................................................................................38

INVESTIGATOR DECLARATION PAGE:..........................................................................................................40


GENERAL GUIDELINES

Overview of Guidelines:eCRF Completion Guidelines provide assistance for completing eCRF pages. Pages that are repeated throughout the eCRF will only be described once. For any additional questions regarding eCRF completion guidelines, please contact the Pfizer Monitor.

General guidance: All textual data should be entered using the English language. eCRF must be completed for all subjects who signed an Informed Consent. To prevent a backlog of data entry, data from the subject’s files/charts should be entered into the

eCRF within 48 hours of assessments being completed. Attention to correct spelling and accurate information is important. Where appropriate use clear and

concise medical terminology. Do not use abbreviations. When entering the numeric value ‘0’ (zero) ensure the ‘0’ (zero) key is used and not the letter ‘O’. Do

not use letters to spell out a number on the eCRF. When entering numeric values ensure a ‘.’ (period) is used to represent a decimal place. Do not use a

‘,’ (comma) or other symbol to represent a decimal place. Do not enter fractions. When entering numeric values with multiple zeros do not use a ‘,’ (comma) to separate zeros. Enter

the numeric value the same way as using a calculator. Answer every question if applicable. Do not leave spaces or blank boxes unless otherwise specified. Ranges cannot be used (i.e., medication start date was between 1975 and 1977). One date/number

must be provided. If primary source documents indicate more than one start date, record the most recent date. If primary source documents indicate more than one number, record the most conservative number.

Adding Comments: Record comments directly on the eCRF only when requested. Do not use a comment field to enter

comments unrelated to the question being asked. Use the Investigator comment function sparingly and ONLY when further explanation of data is

necessary and there is no explicit question for this information on the eCRF (for example, do not enter AEs, medications, or medical history as comments).

Date: All dates (day/month/year) should be recorded in the following format DD-MMM-YYYY. Complete

dates are required for all time points during the subject’s participation in the study. Please note that the alphabetical identifier for month will be used. Four digits must be used for year.

January = JAN February = FEB March = MAR April = APRMay = MAY June = JUN July = JUL August = AUGSeptember = SEP October = OCT November = NOV December = DEC


Time: Enter times as recorded on CRF in format HH:MM. ALL “times” recorded in the CRF must be entered using a 24-hour clock. If a procedure was done

at midnight, enter 0000 (ensuring that the date entered reflects the appropriate day)-Example: 6:00 AM = 0600 6:00 PM = 1800

6:30 AM = 0630 6:30 PM = 1830You do not need to enter the colon. For example, 2010 will convert to 20:10.

Use “UNK” to denote a missing time. Do not use any other method (e.g., 00, --)

Below is a list of appropriate unknown or missing responses:

Not Done vs. None: Not Done on the eCRF should be used when an assessment was not completed (e.g., No Vital

Signs were taken for a protocol-specified time point.) None on the eCRF should only be used when an assessment was completed but no data

were reported (e.g. No Concomitant Non-Drug Treatment/Procedures) [refer to your training materials for general functionality]).

Instructions for Missed Assessments within a Visit If a subject was seen for a visit, but some assessments were not done, complete the header

information and check the “NOT DONE” box. All CRF pages for an attended visit will be collected. If there is no “NOT DONE” box on the module/page, then mark the page as ‘Blank’.

Instructions for Sub-Study Pages within a Visit If a subject is NOT in the sub-study complete the header information and mark the page as ‘Blank’.

[refer to your training materials for general functionality].

Instructions for Missed Visits A visit will be considered missed if it has not been completed prior to the next scheduled visit. If a subject missed a complete visit, do not complete any of the pages for that visit. Do not

mark as blank. Do not mark as not done. Record an investigator comment at the next attended visit acknowledging the missed visit and

DO NOT do anything else to the visit pages (i.e. do not mark as blank, do not mark as not done).

Instructions for Early Terminations Remember to fill out the Early Termination pages if the subject returns for Early Termination

procedures. The date of visit on the ET pages would be the date the subject completed his/her early termination visit. If the ET procedures must be divided over more than one day, the date of visit should be the last date a procedure is completed for that visit.

If a subject discontinues from the study, select “Not Done” for all of the procedures that were not completed during the same visit date. For the subsequent days, there is no need to complete pages. For example, if a subject early terms after the Month 6 visit, you do not need to fill out


Missing / Unknown Information For OC-RDC enter

any form of “unknown” /entire date unknown UNK

any form of “not done” ND

any form of “not applicable” NA

Day missing in date 00SEP2005

Month missing in date 22002005

Year missing in date 22SEP0000

pages for Months 7 – Month 24. Only the End of Study pages (e.g., concomitant drug, concomitant non-drug treatment, disposition modules) and relevant AE pages should be completed.

Instructions for Screen Failures: Screen Failure subjects require completion of the Demographic Data page (page 1) of the Screening Visit, the Subject Summary in the End of Study Visit, and the Investigator Declaration Page.

IMPORTANT: If a subject screen fails at the S2 visit the ECG page must be completed as ‘DONE’. This will trigger payment for this visit else the payment to the site will only be for S1 (if the ECG was not performed at S2, complete the Physical Examination page at S2).

If subject screen failed due to lab abnormalities, the lab requisition date (lab draw date) should be captured as the screen fail date on the subject summary page.

Source Documents: The Pfizer Monitor will verify the accuracy of eCRF data against the source documents. Source

documents and raw data used to complete the eCRF (hospital charts, lab reports and study-specific source sheets) must be available on file and accessible for review by the Pfizer Monitor at each site visit. These source documents should contain the Pfizer subject ID and study number (e.g., A1234567). Originals for transcribed data (clinical lab reports, ECGs, physicals, etc.) MUST be kept in the source file.

Page Types: There are four types of eCRF page types—Scheduled Visit, Unplanned Pages, Log, and EOS (End of Study)

Scheduled Visit Pages: Are used to capture data on a visit by visit basis. Separate pages are provided for each protocol scheduled visit including Follow-Up and Early Termination visits.

Unplanned Pages: Additional eCRF pages (unplanned pages) for selected study procedures may be provided. Use the unplanned pages in the event that a repeat test is required. Data points not pertaining to the repeat test should be left blank (i.e., repeat vitals were done in the sitting position; spaces for standing and supine vitals measurements should be left blank). Refer to you training materials for general guidance.

NOTE: Unplanned visits must be created and inserted in the appropriate unplanned sections (after AE Log). Do NOT insert unplanned pages anywhere else in the OC-RDC system.

Log Pages: These capture data in a cumulative way and are used to record recurring data. All log pages must be opened and entered at least once. “None” or “Not Done” box should be checked if there is no data to be entered. Examples of Log pages in this study are (1) Concomitant Drug Treatment, (2) Non-Drug Treatment/Procedure (3) Adverse Event (AE) Report. Remember, you can add more Log pages as needed. After you close the completed log page, go to the Menu Bar and click on Insert and then on Visit. A new log page will be added and will open.In order for data management to be able to detect discrepant data early, certain pages must be marked as ‘Complete’ prior to the End of the Study.

The following pages are now to be marked COMPLETE once the initial data has been entered:

Dosing Log Page (mark complete once Day 1 Dose is entered) Concomitant Log Page (mark complete once Day 1 data is entered*) Non-Drug Log Page (mark complete once Day 1 data is entered*)

*If no Day 1 data exists, the page should be marked complete upon first data entry.

End of Study Page: This is the page used when a subject’s participation in the study ends. Every subject will need the Subject Summary page completed.


SUBJECT DATA

Screening Failures Screen Failures are subjects who have completed Informed Consent but have not been randomized

into the study to receive study treatment.

Randomized Subjects: Randomized Subjects are subjects who have met all entry criteria and are randomized whether they

early term or complete the study. Randomized Subjects require all visit assessments and log pages to the point of discontinuation (if

early termination occurs) or through study completion in the eCRF if the visit was completed as well as the log pages, end of study page, and investigator declaration page.

Subject Identifiers: Single Subject ID Number (SSID Number):

Each subject will be assigned a unique 8-digit Subject ID. The first four represent the center number (e.g. 1001, 1002 and 1003) and the last four are unique to the patient. The subject ID is obtained from the telerandomization system (IMPALA) at the time of screening. For the most part, the SSID number is what is used to identify the subject.

The Subject ID is to be selected into OC-RDC from the dropdown list in the Insert a New Patient box. Once selected, the Subject ID will appear in the Patient Detail window and the application will copy this onto every CRF page automatically.

Randomization Number: The randomization number is also assigned by IMPALA. It is a 4-digit number that is used to assign the blinded treatment (i.e., study drug or placebo) that the subject will receive. It is entered only once into OC-RDC on the Randomization page in the Day1 visit pages.

HEADER INFORMATION

All Header fields will be pre-populated except for DATE OF VISIT.

Visit Dates: If the Date of Visit is not the same on every page of the visit (for example, a subject returned the next

day to complete the Screening assessments), a comment should be recorded in the Investigator Comment field for the first field on the eCRF page. A query will be issued if a comment is not present.

All visit dates must be on or after the Informed Consent Date. The same visit date cannot be used for multiple visits (e.g., Month 1 and Month 2 cannot have the same visit date).


1001

DEMOGRAPHY:

Date of Birth: Enter the date of birth

Sex: Select appropriate sex.

Height & Weight: Enter height and weight in the appropriate units (i.e., inches/centimeters, pounds/kilograms). Indicate with an “x” to indicate the units of measure.

Weight should be recorded up to 1 decimal place if possible (i.e., 146.41). Height may be recorded up to one decimal place. Do not use fractions.

Race: Select appropriate race as provided by the subject. If the subject’s race does not correspond to one of the categories provided, check “other” and specify the race in the space provided (e.g., for a subject who is American Indian, or Bi-Racial, check “other,” and record the appropriate race).


MENOPAUSAL STATUS:

If subject is female, place "X" in the appropriate menopausal status box. If the subject has not yet undergone menopause, then choose premenopausal If the subject has undergone menopause, then choose postmenopausal. Postmenopausal is

defined as the time after which a woman has experienced twelve (12) consecutive months of amenorrhea (lack of menstruation) without a period. For a female who has had surgery, postmenopausal is defined as a surgical record detailing a prior hysterectomy with bilateral oophorectomy.

If the subject is male, then mark this page as blank.

DRUG ALLERGIES:

Drug Allergies: Place “X" in either Yes box or No box to indicate the presence or absence of drug allergies (other allergies will be listed in medical history section). If "X" is placed in No box, leave the remainder of the module blank. Efforts should be made to differentiate a true drug allergy from a drug intolerance, which should not be captured in this module.

Drug Name: If "X" is placed in Yes box enter the generic drug name (one per line). If the generic name is not known, or if it is a combination product, enter the brand name (Example: Ortho-Novum 7/7/7). DO NOT enter the total daily dose, number of tablets, or any other information in this section. This information is not required.

Type of Reaction: In the space provided indicate the type of reaction (e.g., rash, sneezing, hives) caused by each drug name or class.


LABORATORY SAMPLES (USED FOR ELECTRONIC LABORATORY DATA TRANSMISSIONS):

Not Done: Check the “Not Done” box if the lab was Not Done for any reason.

Fasting Status: Mark an "X" in the appropriate box for fasting status. Subject must be fasting 10 hours prior to lab data being obtained (for noncompliant subjects who did not fast, in the Fasting box enter ‘No’).

NOTES: MDS is the Central Laboratory for this study. The actual lab data (tests, results, reference ranges) will be loaded electronically on a periodic

basis. You will see a separate electronic data file within the specified visit. The laboratory should not transmit data that is not required by the protocol. Ensure that the printout from the laboratory matches the CRF with regard to the following: subject

number, DOB, sex, date of sample vs. CRF page date, PI’s name. You are not required to check that the lab results in the lab load match your lab report.

In the case of a repeat lab test, an unplanned laboratory page needs to be completed. The original lab report should remain onsite with the subject's records. No lab reports should be sent to Pfizer, or sent in with CRF pages. Each lab report needs to be reviewed, signed and dated by either the PI or a medically qualified

sub-PI. Any out of range lab values should have a notation of NCS or CS written next to them on the lab report itself. See the Source Documents section of these guidelines to ensure the lab report is accurately documented for this subject.

Any corrections to lab reports should be discussed with the Central Lab directly by the site. Due to the nature of the lab tests, a faxed copy of the lab report may be reviewed prior to receipt of

the final report. It is the site’s discretion whether or not to keep multiple copies of the lab reports. It is the site’s responsibility to ensure that the appropriate, complete version of the lab report is kept on file, and that it is reviewed, signed and dated (including alert values), by the Investigator.

All clinically significant abnormal test results will be repeated at appropriate intervals, as specified by the protocol or determined by the Investigator or the Pfizer clinician, until they resolve or stabilize to a level considered acceptable. When performing any unscheduled lab tests to monitor patient safety, include the results on an unplanned visit lab page.

When to report findings as an Adverse Event:1) Abnormal laboratory tests must be recorded on an Adverse Event Report log page if they meet ANY of

the following criteria: a) associated with accompanying symptoms b) requires additional diagnostic testing (not including repeating the lab test)c) requires medical/surgical intervention (additional drug treatment or other therapy)d) leads to a change in trial dosing or discontinuation from the studye) is considered to be an adverse event by the Investigator or Sponsor


VITALS:

Not Done: This box should only be selected when a required procedure for a specific time point was not done, for any reason. If some but not all vital signs were collected and recorded appropriately, the vital signs that were collected, as well as any individual vital sign not collected, should be marked as ND.

Actual Time: Enter the actual time the measurement was taken, using the 24-hour clock.

Note: When entering the duplicate measurements you will need to complete the times for each of the repeats first before OC-RDC will allow entry into the blood pressure fields.

Blood Pressure: Record numeric value of blood pressure (systolic/diastolic in mm Hg) taken.

Pulse Rate: Enter the pulse rate

Weight: Weight can be recorded to 1 decimal. Select the unit of measure by checking the appropriate box.

Waist Circumference: Record the circumference to one decimal place. Select the unit of measure by checking the appropriate box.

Note: All vitals measurements are recorded in duplicate measurements. Record each of the two measurements. If vitals were repeated beyond the two repeats, the original readings would be listed on the original page and any additional repeats would be listed on an “Unplanned Vitals” page.


ECG:

Not Done: Select “Done” if the ECG was completed. Select “Not Done” if the ECG was not done for any reason.

ECG data will be loaded electronically on a periodic basis. You will see a separate electronic data file within the specified visit.

ECGs will be performed using the MTX-2 machine ECG System and will be transmitted electronically to Covance Cardiac Services for analysis. The trace and the ECG analysis report (from Covance) must be reviewed by a physician, dated, and initialed and kept in the subject’s binder.

The complete study number and subject ID should be written on each tracing.

If any ECG is repeated or done for safety reasons, an unplanned ECG page must be completed. If an ECG not required by the protocol, but required by the sites SOPs is done, it does not need to be submitted, unless there are safety findings.

When to report findings as an Adverse Event:a. ECG abnormality must be recorded as an adverse event if result:

i. Is associated with accompanying symptoms, and/or ii. Requires additional diagnostic testing (excluding repeating the ECG) or medical/surgical

intervention, and/oriii. Leads to a change in study dosing or discontinuation from the study, significant additional

concomitant drug treatment, or other therapy, and/or iv. Is considered to be an adverse event by the investigator or sponsor.


PHYSICAL EXAMINATION:

Not Done: Place "X" in NOT DONE box if entire physical examination is not done. If "X" is placed in NOT DONE box, leave remainder of module blank.

Status Field: For each site, indicate Normal, Abnormal, or Not Done by placing "X" in the appropriate box. If "X" is placed in Normal box, leave remainder of fields for that site blank. If "X" is placed in Abnormal box, and describe the abnormality in the space

provided. If abnormality is also recorded as an adverse event, be consistent with terminology.

If "X" is placed in Not Done box if the site was not assessed during the physical examination. If marked Not Done, then leave remainder of fields for that site blank.

Screening Visit Physical Exam: This is a full physical exam page which is intended to capture any pre-existing conditions prior to the subject dosing. If an abnormality is noted during this exam there should be corresponding entry on the medical history module.

Subsequent Visit Physical Exams: These will be brief physical exam pages (less sites than on the Screening Visit Physical Exam page). At the bottom of this page you will see the following:

Have there been any significant changes since the previous physical examination?

Check YES if there has been a change from the previous Physical examination. Record the new or changed significant findings in the space provided under If Yes, Specify. Only report clinically significant changes.


o In the judgment of the investigator, clinically significant changes that represent a worsening in physical examination findings (abnormalities) will be recorded as Adverse Events.

Check NO if there has not been a change from the previous physical examination, do not write comments in the If Yes, Specify Section.

Check NO PREVIOUS if the previous exam was not performed.

If yes, specify

Record any new or changed significant findings since the previous physical examination. Follow these guidelines:

Be clear and concise. Do not use abbreviations or symbols (e.g., ↑). Use preferred medical terminology. If the finding is considered by the investigator to be an Adverse Event, also record on the Adverse

Event Page and ensure that the terminology is consistent.

SUB-STUDY PARTICIPATION:

SUB STUDY ONLY:If the site is not participating in the sub study, then mark the page as blank.

Yes/No: If the subject is participating in the sub-study, check YES. If the subject is not participating in the sub-study, check NO.

If the subject was scanned for the sub-study however the scan was rejected due to subject size or other reasons and the subject can not participate in the sub-study, this box should be checked NO.


MEDICAL HISTORY:

Medical History is a disease or syndrome that is ongoing at or stopped before the first dose of study drug. The Medical History page is in the Screening Visit area, but may be updated if any new findings are found prior to dosing on Day 1. IMPORTANT NOTE: DO NOT COLLECT OBESITY AS A MEDICAL CONDITION.

Not Done: If medical history is not done place “X” in NOT DONE box and leave remainder of module blank.

No Significant History: If medical history is done and there is nothing significant findings, select “No Significant History” and leave remainder of module blank.

Disease/Syndrome or Non-Drug Allergies: These fields are pre-populated. If the medical history notes significant findings, check the

corresponding disease(s)/syndrome(s) or non-drug allergy(ies) on the lines provided as Past or Present and enter the Pertinent Details.

Past/Present/Not Applicable: For each disease/syndrome and non-drug allergy indicate if it is PAST or PRESENT or NOT APPLICABLE by placing “X” in the appropriate box.

Past describes a disease/syndrome or non-drug allergy that was previously experienced by the subject but is now resolved.

Present describes a disease/syndrome or allergy the subject is experiencing now, no matter how long the condition has existed. A condition that manifests itself intermittently or seasonally (e.g., migraine headache, pollen allergy) that continues, though not evident at the time the medical history is done, is considered Present. Disease/syndrome or non-drug allergy currently responding to drug or non-drug treatment is considered Present even if symptoms are not evident when medical history is done.

Not Applicable should be checked if the Medical History does not indicate the subject has a history of that Disease/Syndrome or Non-Drug Allergies.


Pertinent Details: For each disease/syndrome and non-drug allergy, record pertinent details (e.g., onset/resolution date, surgical procedure, etc.) on the line provided. Avoid abbreviations and use appropriate medical terminology.Note: Drug/non-drug treatments listed as pertinent details must be recorded consistently in concomitant treatment section.

Other Medical History Page: There is an additional Medical History page which allows you to enter the disease/syndrome or allergy. This should be used if the Medical History indicates a condition that is not listed on the main medical history page. When entering the disease/syndrome or allergy, please use proper medical terminology and avoid abbreviations. Record symptoms individually, only if a diagnosis cannot be made.


DXA SCAN:

SUB STUDY ONLY:If the subject is not participating in the sub-study, then mark the page as blank.

Not Done: If an individual scan was not obtained, then the “Not Done” box should be checked. This page should also be marked as Not Done if the subject was scanned however the scan was rejected and the subject can not participate in this portion of the sub-study, Please insert an investigator comment to this effect to avoid discrepancies.

Actual Date: Enter the actual date the scan was performed.

CT SCAN:


Not Done: If an individual scan was not obtained, then the “Not Done” box should be checked. This page should also be marked as Not Done if the subject was scanned however the scan was rejected and the subject can not participate in this portion of the sub-study, Please insert an investigator comment to this effect to avoid discrepancies.

Actual Date: Enter the actual date the scan was performed.


ALL QUESTIONNAIRES:

THREE FACTOR EATING QUESTIONNAIRE (TFEQ)

Not Done: If this questionnaire was not done place “X” in NOT DONE box and leave remainder of module blank.

Language: Select the language the questionnaire was given to the subject.

Responses: Transcribe the responses as the subject has indicated on the questionnaire in the appropriate box. If a subject left a question blank, insert an investigator comment stating such.

POWER OF FOOD SCALE (PFS):




IMPACT OF WEIGHT ON QUALITY OF LIFE (IWQOL-LITE):




PATIENT HEALTH QUESTIONNAIRE-9 (PHQ-9):





The last question should only be answered if the subject answers any of the questions 1-9 as:

Several days(1)

More than half the days(2)

Nearly every day(3)

If questions 1-9 were not answered as such, the last question may be blank and the question should remain blank in RDC.

PATIENT HEALTH QUESTIONNAIRE GENERALIZED ANXIETY DISORDER QUESTIONNAIRE – 7 (GAD-7):




The last question should only be answered if the subject answers any of the questions 1-9 as: Several days

(1) More than half the days

(2) Nearly every day

(3)

If questions 1-9 were not answered as such, the last question may be blank and the question should remain blank in RDC.

PHARMACOGENOMIC SAMPLE COLLECTION:

Sample Collection Not Applicable: If sample collection is not applicable (for example if the subjects opts not to have the pharmacogenomic sample collected), place "X" in SAMPLE COLLECTION NOT APPLICABLE box and leave the remainder of the form blank.

Was sample collected and specific written informed consent for pharmacogenomic analysis given? Place "X" in Yes box if sample was collected AND specific written informed consent was obtained and record the date the sample was collected. Place "X" in No box if sample was not collected and/or specific written informed consent was not obtained and leave Date of Sample Collection blank

If Yes, Date of Sample Collection: Enter the date the pharmacogenomic sample was collected.


PHARMACODYNAMICS:

___________________________________________________________________________

SUB STUDY ONLY:If the site is not participating in the sub study, then mark the page as blank.

Not Done: Select “Done” if the sample was collected. If the sample was not collected, then the “Not Done” box should be checked. Actual Date: Enter the actual date the sample was collected.

Actual Time: Enter the actual time the sample was collected.

Unique Sample ID: The Unique Sample ID is pre-printed according to protocol specifications.

SMOKING CLASSIFICATION:

Never Smoked: Check “Never Smoked” if subject has smoked less than a total of 100 cigarettes, cigars, pipes, etc. per lifetime.

Ex-Smoker:Screening visit: Check ‘Ex-Smoker” if the subject has smoked more than a total of 100 cigarettes, cigars, pipes, etc. per lifetime however is no longer smoking currently.Subsequent visits: Check ‘Ex-Smoker’ if the subject self reports being an ex-smoker at this visit.

Smoker:Screening visit: Check “Smoker” if subject has smoked more than a total of 100 cigarettes, cigars, pipes, etc. per lifetime and is smoking currently.Subsequent visits: Check ‘Smoker’ if the subject self reports being a smoker at this visit.


ALCOHOL CLASSIFICATION:

D oes the subject drink alcohol: Screening: Check “No” if subject does not drink. Check “Yes” if the subject drinks even if only occasionally.

Subsequent visits: Check “No” if the subject self reports not to be drinking anymore. Check “Yes if the subject self reports drinking even if only occasionally.

If Yes, specify:Indicate the total number of alcohol units consumed per week using the following conventions (no decimals):

Beer= 1 glass=1unit Wine= 1 glass=1unit Spirits=1 measure/shot=1unit For occasional drinking use 0 unit

RANDOMIZATION:

Enter the subject’s randomization number:

This is a 4-digit number assigned by Impala. Left justify No leading zeros


DIETICIAN CONTACT:

Yes/No: If the Dietician made contact with the subject, check YES.

If the Dietician attempted to contact the subject however the subject was NOT spoken to, check NO.

PHARMACOKINETIC SAMPLES:

TROUGH PHARMACOKINETIC SAMPLES

Trough Pharmacokinetic Samples are collected prior to dosing.

PK Not Done: Select “Done” if the sample was collected. Check the “PK Not Done” box if no samples were collected.

Date: Enter the actual date the sample was collected.

Actual Time: Enter the actual time the sample was collected, using the 24-hour clock.

Unique Sample ID: The Unique Sample ID is pre-printed according to protocol specifications and does not need to be entered.


RANDOMIZED SPARSE SAMPLING PHARMACOKINETIC SAMPLES


PK Not Done: Check the “PK Not Done” box if no samples were collected.

Not Done: If an individual sample was not collected, then the “Not Done” box to the left of the appropriate nominal timepoint should be checked.

Actual Date: Enter the actual date the sample was collected.

Time Post Dose: Please note that the Time Post Dose (TPD) values entered are just placeholders in the database. The picture shown here is for the Month 2 PK Sparse Sampling which is actually supposed to take place between 2 – 6 hours TPD. One sample should be taken between 2-6h TPD with a second sample taken at least 30 minutes later. In the CRF, you should enter the first sample in the line for 2 H TPD and the second sample in the line for 2 H 30 MIN TPD.

A similar page is used in Month 3 for PK Sparse Sampling for a 6-12H TPD window. In this CRF, you should enter the first sample in the line for 6 H TPD and the second sample in the line for 6 H 30 MIN TPD.

Actual Time: Enter the actual time the sample was collected, using the 24-hour clock.

Unique Sample ID: The Unique Sample ID is pre-printed according to protocol specifications and does not need to be entered.


DETAILS OF DOSING:

For all PK samples, the 2 most recent doses will need to be recorded. For Trough Pharmacokinetic samples these will be the doses for the 2 DAYS PRIOR TO THE PK

DATE. For Randomized Sparse Sampling Pharmacokinetic samples, these will be the 1 DAY PRIOR TO

THE PK DATE AND THE DAY OF THE PK DATE.

Subjects are being given reminder cards to be used as source documents for this information.

Not Done: Select “Done” if the sample was collected. If recent dosing information was not collected, then the “Not Done” box should be checked.

Date of Last Dose: Enter the actual date of the most recent dose.

Time of Last Dose: Enter the actual time of the most recent dose.

Date and Time of Second Most Recent Dose: Enter the actual date/time of the second most recent dose.


SUBJECT SUMMARY

It is intended that the Investigator will always complete this page for each subject, including subjects that complete the study, screen failures or discontinued subjects.

Visit Date: The visit page should be consistent with the last visit to the site, last contact with the subject (i.e. date of certified letter sent), or the last unplanned follow-up event.

SUBJECT SUMMARY (SCREEN FAILURE)

If subject does not meet entry criteria or is not randomized into the treatment phase of the study for whatever reason, complete the Subject Summary Page in the END OF STUDY Folder.

Subject Was Withdrawn:Withdrawn During Screening: This option applies to a withdrawal from the time after the signing of the Informed Consent Form and prior to dosing.

Reason for Withdrawal/Specify:Did Not Meet Entrance Criteria: This option applies to a withdrawal from the time after the signing of the Informed Consent Form and prior to dosing. An Inclusion Criteria was not met and/or an Exclusion Criteria was met.

Specify which criteria were not met in the space provided using the following choices:

Out of range BMI Blood pressure high/low Dyslipidemia requiring new or change in treatment Diabetes/high glucose Current or history of renal disease Out of range lab values (specify which one) HIV history Malignancy history Drug absorption issue/previous surgical procedures for weight loss CNS history Recent change in smoking habits Marijuana history Alcohol history History of an eating disorder Fluctuation in body weight in past 3 months Completion of the food/exercise log during screening nonsatisfactory Exclusionary concomitant medication (specify) Other (specify)

Subject no longer willing to participate: Provide any details on withdrawal reason.


SUBJECT SUMMARY

Please select one of the following:

Subject Completion or the Reason for Withdrawal:

Subject Completed: Choose this option if the subject completed all study procedures required by the protocol up to Month 24. If a subject completes Month 24, the subject is considered ‘Complete’, regardless if they came in for the follow-up visit or not.

Subject Was Withdrawn: If the subject was withdrawn for any reason you must choose one of the following:

During screening: This option applies to a withdrawal from the time after the signing of the informed consent and prior to dosing.

During active/double-blind treatment: This option applies when the subject is withdrawn after dosing on Day 1 until 24 hours after the end of the treatment period (Month 24). Note: ODIS subjects are still considered to be on treatment, even if they are not receiving study drug treatment.


During post-treatment follow-up period: This option is for any study and applies to the timeframe from 24 hours after the end of the treatment period until the end of study.

Reason for Withdrawal: Choose only one reason for withdrawal. If there are two or more reasons for withdrawal and an AE is one of them, the AE is considered the primary reason for withdrawal unless the subject has died, in which case death is considered the primary reason for withdrawal.

Adverse Event(s): If a subject is withdrawn from the study due to an AE, either by the Investigator or by the subject himself or herself, then this box should be checked. (The applicable AE should have an action of Withdrawn from Study on the AE page).

Laboratory Abnormalities: If there is a significant laboratory abnormality that results in the subject being withdrawn from the study, this box should be checked. (This abnormal laboratory result should be recorded as an AE with an action of Withdrawn from Study on the AE page).

Subject Died: If the subject died, select this box and specify the date of death and cause. If available, provide a copy of the autopsy report in the source documents and provide it to the study team. (The death should also be reported as an SAE only—this is not an AE).

Protocol Violation: If the subject violated any of the requirements of the protocol, they should be removed from the study, and this box should be checked. Specify the particular violation on the Specify line.

Lost to Follow-up: This should be selected if the primary reason the subject was withdrawn from the study is an inability to contact the subject and the subject has not presented for scheduled visits. If the primary reason for discontinuation is Lost to Follow-up, information concerning attempts to contact subject for final visit must be recorded in the subject’s source document/chart. This information should include method of contact (e.g., letter, phone call) and the date of each attempted contact. Three attempts must be made to contact the subject, one of which should be a registered letter; and all 3 attempts must be documented.

Does Not Meet Entrance Criteria: This should be selected if a subject was included in the study and after dosing you discover the subject should not have been enrolled and the subject must be discontinued. This occasionally happens if information that was not available to you while determining eligibility. For example, if the subject does not inform you of a drug abuse history of LSD, but you discover it during the study. Choose from the list below and enter this text into the details section:

Out of range BMI Blood pressure high/low Dyslipedemia requiring new or change in treatment Diabetes/high glucose Current or history of renal disease Lab values (specify which one) HIV history Malignancy history Drug absorption issue/previous surgical procedures for weight loss CNS history Recent change in smoking habits Marijuana history Alcohol history History of an eating disorder Fluctuation in body weight in past 3 months Completion of the food/exercise log during screening nonsatisfactory Exclusionary concomitant medication (specify) Other (specify)

Subject No Longer Willing to Participate: If the subject requests withdrawal from study, this box should be selected (i.e., schedule conflict, not tolerating blood draws, changes their mind due to new information concerning the potential adverse effects of the drug).


Withdrawn Due to Pregnancy: If a subject becomes pregnant during the study and is discontinued, this box should be checked.

Other: Any other reason the subject is withdrawn that does not apply to the reasons above place “X” in “Other” box and specify reason on the line provided (e.g., a natural disaster that requires evacuation from site, sponsor termination of study.) If possible, avoid abbreviations.

WEEK 1 FOLLOW-UP VISIT TELEPHONE CONTACT

Not Done: If Follow-Up Visit Week 1 phone call was not made, then the “Not Done” box should be checked.

Yes/No: If Follow-Up Visit Week 1 phone call was made, and the subject was spoken to, check YES.

If Follow-Up Visit Week 1 phone call was made, however the subject was NOT spoken, check NO.

NOTE: For ODIS subjects, mark this page as BLANK.


DOSING LOG:

Start Date: Enter the date the subject took his/her first dose (i.e., Day 1) or the first date back on dosing for ODIS subjects, using the standard format.

Stop Date: Enter the date the subject took their last dose (i.e., Month 24) or the last date of dosing for ODIS subjects, using the standard format.

If a subject is lost to follow up and dosing stop date is unknown, Default the STOP DATE to the last date the subject can be reasonably inferred to have taken study drug. Also the site must add an investigator comment to the field. (Ex: subject lost to follow-up. This is an estimated stop date. Stop date unknown).” NOTE: DO NOT record dosing interruptions for study drug that was stopped temporarily unless it was intentionally stopped for more that 30 days (ODIS).

NOTE: For all dosing logs that are marked with YES to ‘Was dosing Interrupted’ will be sent a query confirming that the subject was ODIS. The site is to confirm the subject is ODIS in the Internal Comment section of the query then resolve the query. If the subject was not ODIS then the box is to be unchecked in the CRF and the query updated appropriately.

NOTE: In order for data management to be able to detect discrepant data early, this page must be marked as ‘Complete’ after Day 1 dose entry and each entry there after. DO NOT wait until the end of the study to mark this page complete.

Missed medication : We are not capturing study drug compliance other than for those subjects who become ODIS (see definition below).

The following fields are only to be completed for ODIS (Off Drug in Study) subjects:

Definition of ODIS – Intentional interruption AND greater than 30 days

If this occurs: Record the Stop Date as the last day the medication was taken before the missed medication period. Was Dosing Interrupted:

If a subject is ODIS, this box should be checked. DO NOT mark this box for any other dosing interrupted reasons.

Reason for interruption: If the subject is ODIS, select a reason for ODIS. If OTHER is chosen, provide details in the box.

On the next line record the Start Date as the day the medication was re-started.


ODIS SUBJECTS ONLY!!!

CONCOMITANT TREATMENT:

Concomitant Treatment is treatment ongoing at or started on/after Day 1 dosing through the end of study (up to the follow-up visit).

Visit Date: The visit date should be the same as the date of initial data entry into the eCRF page. NOTE: If there were no concomitant treatments, the visit date should be consistent with thedate of the Subject Summary module.

None: Select “Some” if there were concominant medications taken during the course of the study. Select “None”, at the end of the study, if no concomitant drug treatment was given during the study.

NOTE: In order for data management to be able to detect discrepant data early, this page must be marked as ‘Complete’ after Day 1 entry and each entry there after. DO NOT wait until the end of the study to mark this page complete. If no Day 1 data exists, the page should be marked complete upon first data entry.

Drug name: If a drug was given during the study, please enter the drug name. The generic name is preferred, but if a combination product is used, then use the brand name. Enter ONLY the drug name, do not enter the total daily dose, frequency, number of tablets, or any other information in the drug name section.

NOTE: If a combination product does not have a brand name it should be split into separate terms, listing each product on separate lines.

Reason: Record indication for the drug treatment. Note: Indications listed in Reason field must be recorded consistently in medical history section if applicable.

Frequency: Record frequency of drug treatment (for example: daily or QD; 3 times per week or TID).

Dose/Unit: Record drug treatment dose including units (for example: 10 mg).

Start Date: Enter the date the treatment was started. If any portion of date is unknown, enter an estimate. If unable to estimate, enter "UNK".


Stop Date/Ongoing: Enter either the date the treatment was stopped or check ongoing if the treatment was continued past the end-of-study start date.

Something is considered a concomitant drug treatment if it is ingested, injected, absorbed, inhaled, or otherwise enters the body for a treatment purpose (for coding purposes, we also consider things applied to the skin as drugs). This includes prescription and over-the-counter medicines, vitamins, and herbal remedies. It also may include such items as prune juice and orange juice when given for adverse events such as constipation and hypoglycemia.

Pfizer must approve any concomitant drugs given during the study prior to use if listed as exclusionary (forbidden) in the protocol. If it is an emergency situation, the Investigator can let Pfizer know after the fact via voicemail and/or e-mail.

Note: A new entry is required when there is a change in dose and/or frequency, or subject has missed treatment for a significant amount of time.

Additional Concomitant Drug Treatment pages can be added as needed. After you close the completed log page, go to the Menu Bar and click on Insert and then on Visit. A new log page will be added and will open.

NON-DRUG TREATMENT/PROCEDURE:

This module collects all non-drug treatments/procedures taken from ongoing at or started on/after Day 1 dosing through the end of study (up to the follow-up visit).

In general, non-drug treatments/procedures include but are not limited to:

Any formal weight loss program should be listed on this page (i.e. Weight Watchers, Jenny Craig, etc) Diagnostic procedures (e.g., electrocardiogram, x-ray, endoscopy) Medical procedures (e.g., radiation therapy, catheterization) Surgical procedures (e.g., cholecystectomy, arthroplasty, hysterectomy) Therapeutic treatments (e.g., physical therapy, sitz bath, psychotherapy, ice packs, Trendelenburg

position, heating pad, etc.)

Visit Date: The visit date should be the same as the date of initial data entry into the eCRF page. NOTE: If there were no concomitant treatments, the visit date should be consistent with thedate of the Subject Summary module.

None: Select “Some” if there were non-drug treatment/procedures performed during the course of the study. The “None” box should be checked if no non-drug treatments/procedures were given during the study.


NOTE: In order for data management to be able to detect discrepant data early, this page must be marked as ‘Complete’ after Day 1 entry and each entry there after. DO NOT wait until the end of the study to mark this page complete. If no Day 1 data exists, the page should be marked complete upon first data entry.

Treatment/Procedure: If a non-drug treatment/procedure was given during the study, please enter the Treatment/Procedure. Enter ONLY the Treatment/Procedure, do not enter the frequency, reason why given or any other

information in this section. Do not use abbreviations. Enter one non-drug treatment/procedure per line. Use non-drug treatment/procedure terminology consistently throughout this form. A repeat test is not considered a non-drug treatment. Do not collect PLANNED study procedures (i.e. I.V. catheter, ECG, etc).

Start Date: Enter the date the treatment was started.

Stop Date/Ongoing: Enter either the date the treatment was stopped or check ongoing if the treatment was continued past the end-of-study date.

Additional NonDrug Treatment/Procedure pages can be added as needed. After you close the completed log page, go to the Menu Bar and click on Insert and then on Visit. A new log page will be added and will open.


ADVERSE EVENTS

Serious Adverse Events that occur from the time of informed consent and up to the first study dose need to be reported via the AEM form; however, they do not have to be entered as an Adverse Event on the eCRF.

Adverse Events that occur from the time of informed consent and up to the first study dose do not have to be entered as an AE on the eCRF.

Serious and Non-Serious Adverse Events that occur after the first study dose must be recorded in the eCRF.

Visit Date: The visit date should be the same as the date of initial data entry into the eCRF page. If there were no adverse events, the visit date in should be consistent with the date of the Subject Summary module.

No Adverse Event (AE): This box should be selected at the end of the study if the subject did not experience any AEs during the conduct of the study.


Adverse Event: Record all observed or volunteered AEs regardless of treatment group or suspected causal relationship to Study Drug on the AE page.

Each AE should be listed separately (i.e., nausea/ vomiting—these are two separate events and should be captured as such).

The exception is when there is a specific diagnosis for a list of symptoms. Then the diagnosis should be listed as the AE, not the individual symptoms. For example, if a subject has rhinitis, cough, and headache, and the Investigator feels the subject had an upper respiratory infection, upper respiratory infection should be entered as the AE. In this case, the date of onset and resolution would be the date the first symptom was reported and the date the last symptom resolved.

Describe the AE as clearly and succinctly as possible using proper medical terminology. For example, if the subject is experiencing pain, indicate where (i.e., abdominal pain vs. knee pain). The AE term must be equal to or less than 50 characters. We will be utilizing MEDDRA for AE coding purposes. If there is no diagnosis, enter the signs and symptoms as different entries.

See Pfizer Dictionary and Coding System section for more details.

Date of onset: Record the date the AE started. If actual date is unknown, record the approximate date. When recording onset date for an objective test abnormality, record date of test as onset date.

Severity: Record the maximum severity of the AE (mild, moderate, severe) as determined by the Investigator. Only one severity should be checked.

Severity is defined as:Mild: Trivial AE not causing any real problem to the subject.Moderate: AE was a problem to the subject but did not interfere significantly with the usual

activities or clinical status.Severe: AE interfered significantly with the usual daily activity or clinical status.

Action: There are actions for both the study treatment dose and the subject.

Study Treatment Dose: Check one box only: Check “No Action” if the drug dosing continued as scheduled. If study drug dose was changed, select one of the four options provided (Increased, Reduced, Stopped Temporarily, Permanently Discontinued).

NOTE: DO NOT record dosing interruptions for study drug that was ‘Stopped Temporarily’ on the dosing page unless it was stopped for more that 30 days (ODIS).

NOTE: If ‘Permanently Discontinued’ be sure to add a stop date on the dosing page.

Subject: Select those that apply:

1. Withdrawn from the study: If the subject was withdrawn from the study due to an AE, this box should be checked. Also ensure that the Treatment Dose section is completed as “Permanently Discontinued.” Only one AE should be checked as the AE causing discontinuation. If multiple AEs are involved, the PI should select the ultimate AE that caused the discontinuation to be determined. (Ensure the Subject Summary page has an action of “withdrawn during active” due to an “Adverse Event”).


2. Treatment given: Check this box if any treatment was given for the AE, and give details in the appropriate Concomitant Drug or Non-Drug Treatment/Procedure page.

3. Other: Check this box if any other action of a medical nature was taken (i.e., vital signs, stress tests) and specify the nature of this action.Note: If vital signs, lab, ECG, etc. are taken because of an AE, a corresponding unplanned vital signs, lab or ECG page should be completed as well.

4. No action: Check this box if no action was taken for the AE.

Do Serious Criteria Apply: Check the “yes” box if any of the specified criteria for SAE applies (as defined in the protocol). Do not confuse the “serious” definition with the “severity” definition. All identified SAEs occurring during the study or within 30 days after the study drug is discontinued or through the last scheduled follow-up visit (whichever is later) must be reported within 24 hours using the AEM form.

Outcome of AE to Date: Check only one box to indicate if the AE is still present (“Yes” box), the status is unknown (“Unknown” box), or has resolved (“No” box). If the No box is checked, provide the resolution date. If the subject dies without resolution of the AE, the “Yes” box should be checked.

Date Resolved: Record the date the AE resolved. If actual date is unknown, record the approximate date.

Causality (to be completed at the time the event resolves or at the end of study) :

Indicate whether or not “In the Investigator’s judgment” the study drug was the most likely cause of the AE.

Check “Yes/Unknown” if the Investigator suspects it is related to the study drug. Note: If causality is unknown and the Investigator does not know whether or not study treatment caused the event, then it should be attributed to study treatment.

Requirements for investigator signatures/initials in source documentation for attribution of AE causality: The PI, or properly delegated and medically trained sub-investigator should initial and date the causality attribution within the source documentation. This documentation establishes that the subject is being properly evaluated by the study medical staff throughout the study for drug safety issues.

Check “No” if the Investigator feels there is another cause for the AE and select one of the following:

Disease Under Study: If the AE is a manifestation of the disease under study (i.e., worsening of signs or symptoms, increase in frequency/severity, and/or the appearance of a new manifestation/complication), and the appearance of the AE during the trial is consistent with the natural history, usual course, or progression of the disease under study, the “disease under study” should be listed as the cause of the AE.

Other Illness: If the AE is a manifestation of a pre-existing illness (i.e., worsening of signs or symptoms, increase in frequency/severity, and/or the appearance of a new manifestation/complication), and the appearance of the AE during the trial is consistent with the natural history, usual course, or progression of the pre-existing illness, then “Other Illness” should be listed as the cause of the AE. If the AE is a manifestation of a new illness not caused by study drug, then “other illness” should be listed as the cause of the AE. The “other illness” should be specified. For example, if the subject develops bronchitis during the study, the AE would be bronchitis, the causality would be other illness: bacterial infection.

Concomitant Treatment (Drug or Non-drug): If another drug or a non-drug treatment is the most likely cause of the AE, specify this treatment. For example, if a normal healthy subject had a bacterial infection that required antibiotics, and the antibiotics caused diarrhea in the subject, the AE would be diarrhea and the causality would be concomitant treatment: Azithromycin. If a drug were being given as part of the protocol-specified treatment, it would not be considered concomitant treatment, but would be considered part of the study drug.


Other: If another event (not caused by Study Drug) is either the AE or the most likely cause of the AE (i.e., a traumatic event such as a traffic accident or an accidental fall, other medical interventions, or other concurrent events or experiences of the subject), specify this event and be as specific as possible. If in the Investigator's judgment, the cause of the AE is unknown but according to him/her it is not caused by the study drug, “No” can be checked and under “other” “unknown but not related to study drug” can be written. This is ONLY IF THE CAUSE IS UNKNOWN BUT IT IS DEFINITELY NOT STUDY DRUG.

Adjudication Case Number:To be completed by an external vendor with the Adjudication case number provided to the site for each separate event.

Additional Concomitant Drug Treatment pages can be added as needed. After you close the completed log page, go to the Menu Bar and click on Insert and then on Visit. A new log page will be added and will open.

Special situations: If an adverse event occurs intermittently during the study, it can be captured as one AE and the word “intermittent” should be added to the AE description, unless it occurs daily at the same time relevant to dosing, in which case it should be captured separately.

All clinically significant abnormal physical exam findings appearing during the study, or changes from screening/baselines, should be recorded as an AE.

An objective test finding should be recorded as an AE if it meets one of the following criteria:1. Test result is associated with accompanying symptoms; and/or2. Test result requires additional diagnostic testing or medical/surgical intervention; and/or3. Test result leads to a change in study dosing or discontinuation from the study, significant additional

concomitant drug treatment or other therapy; and/or4. Test result leads to any of the outcomes included in the definition of a serious adverse event; and/or5. Test result is considered to be an adverse event by the Investigator or sponsor.

Merely repeating an abnormal test, in the absence of any of the above conditions, does not meet the above conditions for reporting as an AE.

Any abnormal test result that is determined to be an error does not require reporting as an AE, even if it did meet one of the above conditions except for condition #4.

If a stress test were done due to an ECG finding, the ECG finding would be an AE. If glucose were infused due to a low glucose lab result, the lab result would be recorded as an AE.

If a lab result comes back outside the normal limits and the Investigator feels it necessary to repeat that lab result, and the lab result comes back within normal limits, it need not be captured as an AE (unless the PI feels it should). If the lab result comes back still outside the normal limits (regardless of the significance of the result), it should be recorded as an AE. The start and stop time of the AE should correspond to the first time the abnormal result was seen and when the result returned to normal.

For laboratory AEs, list each lab abnormality separately, as well as the direction of the abnormality (increased or decreased).

If the severity of an AE changes without the AE stopping and restarting, it should be captured as one AE, with the most severe severity of the AE captured for the whole AE.

SPECIFIC GUIDANCE FOR MOTOR VEHICLE ACCIDENTS OR FALLS: Motor vehicle accidents should be recorded as adverse events when the subject is the operator of the vehicle, even if an injury did not result. When a motor vehicle accident results in an injury, both the injury and the motor vehicle accident should be recorded individually as adverse events. Any motor vehicle accident when the subject is the operator of the vehicle should be recorded as DRIVER IN MOTOR


VEHICLE ACCIDENT to capture the fact that the subject was a driver. A motor vehicle is defined as any mechanically or electrically powered device not operated on rails and includes (but is not limited to) cars, trucks, vans, motorcycles, and off-roads vehicles. Boating accidents occurring where the subject is the operator of a boat operating under power should also be reported in the same way regardless of whether an injury resulted. For example, record “driver in motor vehicle accident” and “concussion” instead of “concussion due to MVA. If the subject was operating a motor vehicle and had an accident, but was not injured, then “driver in motor vehicle accident” should be recorded.

Falls should be recorded as adverse events, even if an injury did not result. When a fall results in an injury, both the injury and the fall should be recorded individually as adverse events. For example, record “fall from ladder” and “fractured right tibia” instead of “fractured right tibia”. If the subject fell but was not injured, then the fall should be recorded (e.g. “fell off porch”).

When recording traumatic injury other than motor vehicle accident when the subject is the operator or falls as an adverse event, record the injury rather than the cause. For example, record “lacerated right middle finger” rather than “cut with kitchen knife”). If the subject was in a motor vehicle accident, but was not the operator of the vehicle, then an adverse event would only be recorded if an injury was sustained and then only the injury itself is recorded, not the motor vehicle accident.

Note: Pregnancy is not considered an AE unless the result is a stillbirth, miscarriage, or deformity. It is the Investigator’s responsibility to follow the pregnancy through until term. An Exposure in Utero form will be completed by the site and sent to the SAE vendor.

PFIZER DICTIONARY AND CODING SYSTEM

The AE, medical history, drug, and non-drug treatment terms will be coded once entered and you might be queried if the system cannot achieve this process correctly. A query can be generated for several reasons, and the data manager will assist you in the discrepancy resolution. Here is list of practical tips that should help you avoid the most frequent problems:

A term must: Be a “stand alone” concept Be specific ("congestion" - is it nasal, pulmonary, liver, cardiac, etc.) Be a single medical concept Not include abbreviations if possible (if used, they should be unambiguous) Use standard medical terminology Be in English Be spelled correctly When a drug label is requested enter the drug name exactly as it appears on the drug label

Avoid colloquialisms: “Messed up” instead of depressed mood “Wishy-washy” instead of distractibility “Black cloud feeling” instead of cognitive impairment Some terms are not acceptable: vagueness, crazy, acting goofy

In general: “due to,” “secondary to” terms should be split; “allergic headache” should be split to “allergy” and

“headache” unless a symptom “due to” a diagnosis or an infection “due to” certain pathogens. modifiers “increased,” “elevated” are used to describe test findings, while “high” is used to describe

medical conditions

Similar terms may be represented differently: Consistency in recording across visits will assist in reducing issues “Blood pressure high” = >PT Hypertension and Vascular disorders system order classes “Increased blood pressure” or “Elevated blood pressure” = >Investigations system order class


Pathogen names alone are not acceptable: “Staphylococcus aureus” is not acceptable and will be queried. (Infection? Presence of laboratory

finding? Other?)

Lab findings: If lab findings meet the criteria of an AE, they will not be interpreted, no matter how obvious. Terms

should specify “increased” or “decreased” in order to be coded as such.

CNS TARGETED ADVERSE EVENT ASSESSMENT

This page builds on the information already entered on the AE CRF page.

Expanded documentation will be done if the targeted AE is of persistent duration or moderate to severe in intensity or associated with other symptoms suggesting a CNS diagnosis or causes distress or functional impairment or precipitates request to discontinue drug or the program or there is clinical concern about the subject’s condition. Expanded documentation will be collected on all CNS targeted AE’s that meet the “required” guidelines, as well as all CNS-related serious adverse events (SAE) and all CNS-related drug discontinuations, even if these are not listed as targeted CNS events.

Not Done: Select “Done” if the AE was a Targeted Event. If AE was not a Targeted Event, then the “Not Done” box should be checked.

Visit Date: The visit date should be the date the CNS Targeted Adverse Event was reported.

Targeted AE Term: Record the exact term as listed on the AE page.


Date of onset: Record the date the CNS Targeted AE started. If actual date is unknown, record the approximate date. This date MUST MATCH the date recorded on the AE page.

1) Functional Impairment:Is the subject employed: if yes answer 1a and 1b. If no, go to question 2.

1a Work Performance Impaired: if yes answer question 1ai, else go to 1b.1b Physical activity impaired: if yes answer question 1bi, else go to question 2.

2) Was there a precipitating event:If yes, check as many boxed as necessary.If no, go to next question.

3) Was a chronic distressing life situation present?If yes, check as many boxes as necessary. If ‘Other’ is checked, describe.If no, go to next question.

4) Was an associated medical condition present?If yes, check as many boxes as necessary. If ‘Other’ is checked, describe.If no, go to next question.

5) Is the subject satisfied with their weight loss? Check yes or no.

6) Does the subject have a history of this event?If yes, answer all questions a-e.a) Previous episodes similar? If yes, describe.b) Previous diagnosis? Check yes or no.c) List previous drug treatments: list any drug treatments given to this subject for this episode in the

past.d) Positive response to drug: Check yes or no if the subject responded positively to the drug

treatments listed in question c.e) Number of previous episodes: enter the number of times the subject has experienced this type of

episode in the past.7) Is there a family history? Check yes or no

8) Out come of this event: Check only one outcome. If c) Subject is under psychiatric or neurological treatment please describe.If d) Other: please specify what is being done.


INVESTIGATOR DECLARATION PAGE:

INVESTIGATOR'S DECLARATION

Investigator Signature:

Date (dd-MMM-yyyy):

I have reviewed this subject's study data and confirm that, to the best of my knowledge, it accurately reflects the studyinformation obtained for this subject.

Please Print Name:

- - 2 0

ICH GCP requires that the investigator ensures the accuracy and completeness of the data reported to the sponsor (ICH GCP 4.9.1) and that the CRFs are signed by the investigator or an authorized member of the investigator's staff to confirm the observations recorded (ICH GCP 8.3.14). Since logging in to OC-RDC does not constitute an electronic signature, the required signature for the CRFs is provided on a non-electronic (paper) CRF page.

An Investigator’s Declaration Page (page 99999) must be signed and dated by the Principal Investigator for all subjects, whether they were Screen Failures, Discontinued Treatment, or Completed the Study.

Note: it is highly recommended that the Principal Investigator signs this page, however, if the responsibility is appropriately delegated to another physician on the Delegation of Authority document, a delegate may also sign.

The Investigator Declaration page is a paper CRF page that is signed by the investigator. Following the patient's End of Study visit, the remaining CRF pages are to be filled out by the site in RDC. The monitor will complete the required monitoring and source data verification of this data and any data queries must be resolved. The monitor will then instruct the site to sign the appropriate Investigator Declaration page and will collect this page at the next monitoring visit. The Clinical Research Site Manager (CRSM) will instruct the site when the Investigator’s Declaration can be signed and provide shipment information at that time.

A CARBON COPY OF ALL INVESTIGATOR SIGNATURE PAGES MUST BE PLACED IN THE STUDY SUBJECT SOURCE DOCUMENTS.
