University of Pennsylvania School of Medicine BufferGel® with diaphragm found to be an effective contraceptive in two Phase II/III trials Kurt T Barnhart,

University of PennsylvaniaSchool of Medicine

BufferGel® with diaphragm found to be an effective contraceptive in two

Phase II/III trials

Kurt T Barnhart, MD MSCE; Univ. of PennsylvaniaJames E Higgins; Health Decisions, Inc.

H Trent MacKay, MD MPH; NICHDDiana L Blithe, PhD; NICHD

Thomas R Moench, MD; ReProtect, Inc.

for the NICHD Contraceptive Clinical Trials Network


NICHD Contraceptive Clinical Trials Investigators

California Family Health Council, UCLA, Harbor-UCLA Medical Center: A. Nelson, R. Frezieres, T. Walsh

Columbia University: C. Westhoff Eastern Virginia Medical School: D. Archer Magee-Womens Hospital: M. Creinin New York University: L. Wan University of Cincinnati: M. Thomas University of Colorado Health Sciences Center: W. Schlaff University of Florida Health Science Center: A. Kaunitz University of Medicine and Dentistry of New Jersey: C. Ayers University of Pennsylvania: K. Barnhart

NICHD, National Institutes of Health, Contract Numbers N01-HD-6-3261, N01-HD-1-33(14-20)


BufferGel

Non-detergent spermicidal microbicide

Potent acidic buffering capacity

Reinforces normal vaginal acidity to inactivate sperm and sexually transmitted infection pathogens

Currently also under investigation in Phase II/IIB for prevention of HIV transmission (HPTN 035)


Study Design Rationale

BufferGel is a spermicidal microbicide, being developed for dual protection (disease and pregnancy).

Diaphragms may increase protection against disease as well as pregnancy. (e.g., MIRA trial hypothesis)

Therefore BufferGel and N9, each with a diaphragm, were compared for contraceptive effectiveness.


PRIMARY HYPOTHESIS

BufferGel® used with diaphragm is non-inferior to Gynol II® used with diaphragm for contraceptive efficacy.

SECONDARY OUTCOMES

Safety of BufferGel with diaphragm: (vaginal and urinary tract infections, genital irritation, and colposcopic lesions)

Acceptability of BufferGel with diaphragm

CCN003


Study Design Study One

Double-blind, randomized 2:1 BufferGel to Gynol II

Study Two

Open-label BufferGel

Subjects used product for 6 cycles (both studies)

Those completing Study One could elect to continue for an additional 6 cycles (total of 12 cycles)


Baseline CharacteristicsCharacteristics

BufferGel(N=621)

Gynol II(N=300)

Age in years (SD) 27.7 (5.8) 28.4 (5.8)

Race (%)

African-American 23 27

White 60 58

Asian 5 5

Other 13 9

Hispanic or Latina (%) 20 17

Never used diaphragm before (%) 80 82

Never used spermicide before (%) 58 56

Married (%) 33 32

Living with partner (%) 68 66

Nulligravida (%) 33 29


Screened: 1333Eligible: 1055

BufferGel with diaphragm: 703 Gynol II with diaphragm: 352

All-treated: 621Used product, pregnancy information available: 615Perfect use: 438

All-treated: 300Used product, pregnancy information available: 297Perfect use: 220

Discontinued before 6 months: 362 -Pregnancy: 54 -Adverse experience: 22 -Noncompliance: 111 -Lost to follow-up: 78 -Other: 97

Discontinued before6 months: 185 -Pregnancy: 29 -Adverse experience: 12 -Noncompliance: 43 -Lost to follow-up: 42 -Other: 59

Entered 6-month extension: 153


Entered 6-monthextension: 81



EfficacyBufferGel Gynol II

Difference 95% CIPopulation

Pregnancy Probability

(%) 95% CI

Pregnancy Probability

(%) 95% CI

6-mo cumulative probability

Intent-to-Treat 10.3 7.7, 12.8 11.0 7.3, 4.6 -0.7 -5.1, 3.8

Modified Intent-to-Treat

10.1 7.1, 13.1 12.3 7.7, 16.9 -2.2 -7.7, 3.3

Perfect Use 4.7 0.9, 8.4 6.1 0.2, 12.0 -1.4 -8.4, 5.6

12-mo cumulative probability

Modified Intent-to-Treat

16.7 10.2, 23.1 17.0 8.2, 25.9 -0.4 -11.3, 10.6

Perfect Use 4.7 0.0, 14.2 6.1 0.0, 18.6 -1.4 -17.1, 14.4


Infectionscumulative through cycle 6

OutcomeBufferGel (n=621)

Gynol II (N=300)

P-value

Symptomatic urinary tract infection

9 (%) 14 (%) 0.03

All urinary tract infections 16 (%) 18 (%) 0.30

Bacterial vaginosis (based on Nugent’s score)

27 (%) 27 (%) 0.94

Symptomatic yeast vaginitis

6 (%) 8 (%) 0.43


Colposcopic Lesions

BufferGel (n=76)

Gynol II (N=35)

P-value

Baseline 42 (%) 40 (%) 0.84Cycle 1 36 (%) 47 (%) 0.19Cycle 3 29 (%) 37 (%) 0.39Cycle 6 29 (%) 29 (%) 0.97

Average # of lesions/woman at follow-up

0.73 1.07 0.2


Side Effects

EventBufferGel (n=528)

Gynol II (N=270)

Irritation, any severity 35 (%) 34 (%)Irritation, moderate or greater severity 9 (%) 11 (%)Partner irritation 12 (%) 10 (%)Vaginal pain 6 (%) 6 (%)Vaginal discharge 6 (%) 4 (%)Intermenstrual bleeding 15 (%) 17 (%)Irregular menstruation 14 (%) 13 (%)

Product discontinued because of AE 3.2 (%) 3.7 (%)


Acceptability at Cycle 6BufferGel (n=528)

Gynol II (N=270)

P-value

Overall impression of method (%) 0.66Liked strongly 24 24

Liked somewhat 44 48Neutral 16 14

Disliked somewhat 13 12Disliked strongly 4 2

Definitely or probably use product if available (%) 68 70 0.56

Pref relative to condoms (%) 54 57 0.50


Summary BufferGel displayed a 6-month typical use

pregnancy rate of 10.1

Side effects were similar in both groups, with fewer symptomatic urinary tract infections in the BufferGel group

68% of subjects using BufferGel would definitely or probably use it if it were available


Conclusion

BufferGel used with a diaphragm is a safe, acceptable contraceptive with efficacy that is non-inferior to Gynol II used with a diaphragm

Evaluation for HIV prevention is ongoing (HPTN 035)

Documents

University of Pennsylvania School of Medicine BufferGel® with diaphragm found to be an effective contraceptive in two Phase II/III trials Kurt T Barnhart,