Contraceptive Effectiveness and Safety of the SILCS Diaphragm

This multi-center contraceptive effectiveness and safety study of the SILCS diaphragm will
enroll approximately 450 couples at risk for pregnancy w at six study sites in the U.S. The
study will randomly assign approximately 300 couples to use the SILCS diaphragm with
BufferGel (BG) and approximately 150 couples to use the SILCS diaphragm with Gynol II (2% N-9
gel). At two sites, a substudy involving colposcopy and microflora will be conducted in about
80 women (40 at each site). For certain evaluations, the data from a contraceptive study
conducted by NICHD of the Ortho All-Flex diaphragm used with either BG or N-9 will be used as
historical controls.

In the current study, each participant will agree to use the SILCS diaphragm with her
assigned contraceptive gel as her only method of contraception for approximately 7 months (at
least 190 days) and at least 6 menstrual cycles. Emergency contraception will be offered if
unprotected intercourse occurs, according to local prescribing practices.

Each female participant will undergo four scheduled visits: Enrollment, After Cycle 1, After
Cycle 3, and Final visits. Two weeks after enrollment, each participant will be called to
determine if she has had any problems with the method and to assess compliance.

Recruitment for this study is expected to take about 12 months. Each subject's participation
will last about 6-7 months. Site closeout is expected to take three months. The clinical
portion of the study should last about 21 months. Data closure and analysis are expected to
take three months and the Final Report two additional months.

Female Inclusion Criteria

In order to enroll into the clinical trial, potential subjects must:

- be healthy sexually active women, at risk for pregnancy and desiring contraception;

- be within the age range of 18 through 40 years, inclusive;

- be at low-risk for HIV or STI infection, currently have (at least 4 months) a single
sexual partner who is also at low-risk for HIV or STI infection, and expect the same
partner for the study;

- have a negative urine pregnancy test ;

- have normal menstrual cycles with a usual length of 24 to 35 days over the last 2
months ;

- have a documented history of at least 6 weeks and two spontaneous, normal menstrual
cycles since last pregnancy outcome, one spontaneous normal menstrual cycle after
discontinuing hormonal contraception or therapy and 10 months since last DepoProvera
injection;

- not be actively desiring pregnancy for approximately 7 months and willing to accept an
unknown risk of pregnancy;

- be willing to engage in at least 4 acts of heterosexual vaginal intercourse per cycle
;

- be willing to be fitted with a standard diaphragm and use the SILCS diaphragm with
assigned study gel during the study;

- be willing to only use the assigned study gel with the SILCS diaphragm as the sole
method of contraception over the course of the study;

- agree not to participate in any other clinical trials during the course of the study;

- be willing and able to comply with study procedures and to return to the clinic for
scheduled follow-up visits; and

- colposcopy and microflora substudy only:

- be willing to avoid using tampons for 72 hours prior to clinic visits or any
intravaginal product other than those provided by the investigator for the
duration of participation; and

- be willing to comply with substudy procedures. Male Criteria

The male partner must be at least 18 years old and must not:

- have a known fertility problem or vasectomy;

- have known risks for STIs including HIV:

- have had more than one sexual partner in the past four months;

- have shared injection drug needles within the past six months;

- have had sex with a man within the past 12 months;

- have, or suspected to have, HIV infection; or

- have been diagnosed with or treated for any STI in the past six months;(with the
exception of recurrent genital herpes or condylomata)

- have a known sensitivity or allergy to silicone, nylon, and/or spermicide or product
containing N-9; and

- have taken an investigational drug or used an investigational device within 30 days
prior to enrollment or previously participated in this study.

Female Exclusion Criteria

In order to enroll into the clinical trial, potential subjects must not:

- have an allergy to silicone, nylon, latex or dry natural rubber products, and/or
spermicides or products containing N-9;

- have a history of toxic shock syndrome (TSS);

- have a suspected or diagnosed UTI or vaginitis, unless treated and symptoms resolved
prior to enrollment;

- have a history suggestive of infertility, defined as any of the following:

- known history of a fertility problem, sterilization, ectopic pregnancy,
hospitalization for pelvic inflammatory disease (PID), or endometriosis unless
participant has had a subsequent spontaneous intrauterine pregnancy; or

- abnormalities on pelvic examination at enrollment that may impair fertility;

- have contraindications to pregnancy (medical condition) or chronic use of class D or X
medications;

- have high risk for HIV or other sexually transmitted infections (STIs):

- have had more than one sexual partner in the past four months;

- have shared injection drug needles within the past six months;

- have, or suspected to have, HIV infection; or

- have been diagnosed or treated for any STI, including Trichomonas vaginalis,
(with the exception of recurrent genital herpes or condylomata) or PID within the
past six months prior to the enrollment visit;

- have signs or symptoms of current cervicitis, endometritis or PID or have clinical
evidence of HSV on exam;

- be lactating or breastfeeding;

- have any abnormal vaginal bleeding or spotting within the month prior to enrollment;

- have any abnormal finding on pelvic examination which precludes her from participating
in the trial;

- have had a vaginal or cervical biopsy within one week or vaginal surgery within the
three months prior to enrollment;

- have an abnormal Pap smear in the past 12 months defined as:

- ASC-US without a normal repeat Pap smear at least 6 months later;

- ASC-US with positive reflex high-risk HPV testing (ASC-US/HPV+) or LSIL except
when a colposcopy was performed (with or without biopsy) and found no evidence of
high-grade disease (CIN II or worse) unless treatment is indicated per local
standard of care;

- ASC-H, atypical glandular cells, or HSIL unless treatment was received and
follow-up at least 6 months after the treatment showed no evidence of disease;

- malignant cells;

- consume (on average) greater than 3 alcoholic beverages per day;

- have a past (within 12 months) or current history of drug abuse ;

- have previously participated in or completed this study;

- have a vaginal or cervical anatomic abnormality that would interfere with the proper
placement and retention of the device;

- have other conditions that would constitute contraindications to participation or
would compromise ability to comply with the study protocol;

- have taken an investigational drug or used an investigational device within the past
30 days; and

- have deep epithelial disruption on colposcopic exam (SUBSTUDY).