Contraceptive Effectiveness and Safety of the SILCS Diaphragm

Contraceptive Effectiveness and Safety Study of the SILCS Diaphragm: the Pivotal Study

This multi-center contraceptive effectiveness and safety study of the SILCS diaphragm will enroll approximately 450 couples at risk for pregnancy at six study sites in the U.S. The study will randomly assign approximately 300 couples to use the SILCS diaphragm with BufferGel 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). The primary objective of this study is to estimate the cumulative 6-month typical-use pregnancy probability for women using the SILCS diaphragm with a contraceptive gel.

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).