Study of the Contraceptive Efficacy and Safety of Amphora Gel Compared to Conceptrol Vaginal Gel

Clinical Trial Design

This is a multicenter, open-label, randomized, controlled, Phase III study of repeated use of
Amphora™ gel compared to Conceptrol® Vaginal Gel as the method of contraception over seven
cycles of use. In addition, there is an opportunity for Amphora™ gel subjects to continue
with study treatment for up to 13 cycles of treatment upon completion of the first seven
cycles of treatment.

A subset of subjects (Amphora™ gel and Conceptrol® Vaginal Gel) will undergo colposcopy at
the Admission Visit and at the visits after Cycles 1, 3, and 7 (Treatment Exit). Subjects
participating for 13 cycles will also undergo colposcopy after Cycles 10 and 13. Colposcopic
photographs will be taken at all visits independent of presence of any suspicious areas. Any
suspicious areas and clinical findings will be recorded on the colposcopy case report form.
The colposcopy evaluator for the subset will be blinded regarding the treatment group of the
subject. If at any time during the study the investigator deems colposcopy necessary,
colposcopy will be performed on any subject and will not be limited to subjects in the
colposcopy subset.

A subset of subjects (Amphora™ gel and Conceptrol® Vaginal Gel) will also have
semi-quantitative cultures for E. coli and clinical yeast performed at the Admission Visit
and after Cycles 1, 3, and 7 (Treatment Exit) Visits. Subjects participating for 13 cycles
will also undergo the assessments after Cycles 10 and 13. Another subgroup will have
quantitative vaginal cultures performed after Cycles 1 and 7 (Treatment Exit) Visits, and
also after Cycle 13 for subjects participating in the extension.

Selected research centers will also recruit subjects into the subset of women 36-45 years of
age at enrollment.

Inclusion Criteria:

- Be healthy women, who are sexually active, at risk for pregnancy, and desiring
contraception.

- Be within the age range of 18 through 35 (inclusive) at enrollment if not in the
subset of women with an age of 36-45 at enrollment (age subset at select sites).

- Be at low-risk for both human immunodeficiency virus (HIV) and sexually transmitted
disease (STD) infection and currently have a single sex partner (≥ 4 months) who is
also at low-risk for both HIV and STD infection.

- Have a negative urine pregnancy test prior to enrollment.

- Have normal cyclic menses with a usual length of 21 to 40 days over the last two
cycles or at least one spontaneous, normal menstrual cycle (two menses) since
delivery, abortion, or after discontinuing hormonal contraception/hormonal therapy.

- Be willing to accept a risk of pregnancy.

- Be willing to engage in at least two acts of heterosexual vaginal intercourse per
cycle.

- Be willing to be randomized to either study treatment.

- Be willing to use the study product as the only method of contraception over the
course of the study (with the exception of emergency contraception (EC)), when
indicated).

- Be capable of using the study product properly and agree to observe all study
directions and requirements.

- Be willing to keep a daily diary to record coital information, product use
information, information about the use of other vaginal products, and sign and symptom
data for both the subject and her partner.

- Agree not to participate in any other clinical trials during the course of the study
with the exception of enrolling in the Amphora™ gel extension study.

- Be willing to give written informed consent to participate in the trial.

Exclusion Criteria:

- Have a history of allergy or sensitivity to spermicides or products containing N-9
(nonoxynol-9).

- Have had three or more urinary tract infections (UTIs) in the past year.

- Have a UTI by urine culture, symptomatic yeast vaginitis, or symptomatic bacterial
vaginosis diagnosed by wet mount unless treated and proof of cure is documented.

- Have a history of any recurrent vaginal infections/disorders (either less than or
equal to four times in the past year or less than or equal to three times in the
previous six months).

- Be pregnant, have a suspected pregnancy, or desire to become pregnant during the
course of the study.

- Have a history of infertility or of conditions that may lead to infertility, without
subsequent intrauterine pregnancy.

- Have any contraindications to pregnancy (medical condition) or chronic use of
medications for which significant evidence of fetal risk exists.

- Have had more than one sexual partner in the last four months.

- Have shared injection drug needles in the past unless has a negative HIV test at least
six weeks since last use.

- Have or have been suspected to have HIV infection.

- Have been diagnosed with genital herpes simplex virus (HSV), with the first occurrence
(initial episode) within three months prior to screening.

- Have three or more outbreaks of HSV within the last year.

- Have evidence of Chlamydia trachomatis or Neisseria gonorrhoeae unless she and her
partner complete treatment and proof of cure is documented.

- Have been diagnosed with any other STDs in the six months prior to the Randomization
Visit (with the exception of human papillomavirus (HPV), trichomonas, gonorrhea, adn
Chlamydia).

- Be lactating or breastfeeding.

- Have any clinically significant abnormal vaginal bleeding or spotting within the month
prior to screening.

- Have any clinically significant abnormal finding on pelvic examination or baseline
labs, which in the view of the investigator, precludes her from participating in the
trial.

- Have clinically significant signs of vaginal or cervical irritation on pelvic
examination.

- Have had vaginal or cervical biopsy or vaginal surgery within three months prior to
screening (with the exception of cervical biopsies performed for eligibility
determination).

- Have used vaginal or systemic antibiotics or antifungals within 14 days prior to
screening or enrollment/randomization, with the exception of systemic antibiotics
taken for a UTI and trichomonas diagnosed at screening. Subjects should not have used
systemic antibiotics prescribed at the Screening Visit for a UTI within seven days of
the enrollment/randomization visit.

- Have had a Depo-Provera® injection in the ten months prior to enrollment.

- Have an abnormal Pap test based on the following criteria:

- Pap test in the past 15 months with ASC-US unless:

- less than 21 years of age;

- a repeat Pap test at least six months later was normal;

- reflex HPV testing was performed and was negative for high-risk HPV; or

- a colposcopy (with or without biopsy) found no evidence of dysplasia requiring
treatment or treatment was performed and follow-up at least six months after the
treatment showed no evidence of disease;

- Pap test in the past 15 months with LSIL unless:

- less than 21 years of age;

- a colposcopy (with or without biopsy) found no evidence of dysplasia requiring
treatment or treatment was performed and follow-up at least six months after the
treatment showed no evidence of disease;

- Pap test in the past 15 months with ASC-H, atypical glandular cells, or HSIL unless
colposcopy and/or treatment was performed and follow-up at least six months after the
colposcopy and/or treatment showed no evidence of disease;

- Pap test in the past 15 months with malignant cells.

- Consume (on average) greater than three drinks of an alcoholic beverage per day.

- Have a past history (within 12 months) or current history which, in the PI's judgment,
constitutes of drug abuse (recreational, prescription, or over-the-counter (OTC)).

- Have taken an investigational drug or used an investigational device within the past
30 days.

- Have issues or concerns (in the judgment of the investigator) that may compromise the
safety of the subject or confound the reliability of compliance and information
acquired in this study.

In addition, in order to be eligible to participate in the trial, potential subjects must
state that, to her best knowledge, her sexual partner meets the following criteria:

- Is not infertile.

- Has had untreated chlamydia or gonorrhea in the past six months.

- Has not had more than one sexual partner in the past four months.

- Has no history of allergy or sensitivity to spermicides or products containing N-9.

- Has not been previously diagnosed with or suspected of HIV infection unless he has
subsequently had a negative HIV test.

- Has not been known to have engaged in homosexual intercourse in the past five years
unless he has had negative HIV test results since then.

- Has not shared injection drug needles in the past unless he has had a negative HIV
test at least six weeks since last use.