AMP002 Phase III Contraceptive Study

Through assessments including pelvic examination, laboratory procedures, and medical and gynecological history, subjects will be screened for eligibility in order to enroll approximately 1349 subjects into the study. After a screening period of up to 60 days, enrolled women will receive study drug. Each woman will participate in the study until after she has completed treatment during seven study cycles. Women who have individual cycles that do not meet the criteria for an evaluable cycle will not have those cycles replaced by subsequent cycles in order to provide a total of seven evaluable cycles.

Inclusion criteria

• Inclusion Criteria:

To enroll in the clinical study, potential subjects must:

• Be healthy women, who are sexually active, at risk of pregnancy, and desiring contraception.
• Be within the age range of 18 to 35 years old (inclusive) at enrollment.
• In the opinion of the Investigator, be at low risk for both human immunodeficiency virus (HIV) and sexually transmitted infections (STIs) based on review of high-risk behaviors and exposures according to the Centers for Disease Control STI Guideline.
• At the time of enrollment, have a single male sex partner for ≥3 months.
• Have a negative urine pregnancy test at enrollment.
• Have normal, cyclic menses with a usual length of 21 to 35 days over the last two cycles or at least two consecutive spontaneous menses (21 to 35 days in length) since delivery, abortion, or after discontinuing hormonal contraception or hormonal therapy prior to the date of consent. In addition:

• If the subject recently discontinued breastfeeding, she must have demonstrated return to regular cycling and have had at least three consecutive, spontaneous menses post-lactation prior to the date of consent.
• If the subject received prior administration of injectable contraceptives (e.g., depot-medroxyprogesterone acetate [DMPA], Depo Provera), there must be at least 10 months since the last injection and the subject must have had at least two consecutive, spontaneous menses prior to the date of consent.
• If a contraceptive implant was recently removed, the subject must have had at least two consecutive, spontaneous menses prior to the date of consent.
• If an intrauterine device (IUD) was recently removed, the subject must have had at least one spontaneous menses following removal and prior to the date of consent.
• Be willing to engage in at least three acts of heterosexual vaginal intercourse per cycle.
• Be willing to use the study drug as the only method of contraception over the course of the study (with the exception of emergency contraception [EC] in the event a subject engages in vaginal intercourse but believes that the study drug was not used properly or she is at risk for pregnancy for any other reason).
• Be capable of using the study drug properly and agree to comply with all study directions and requirements, including retaining the wrappers and returning them to the clinical site at the next study visit.
• Be willing to keep a daily electronic diary (eDiary) to record coital information, study drug use information, use of concomitant medications including other vaginal products and other contraceptives, menses, and sign and symptom data for the subject or as reported to her by her partner.
• Agree not to participate in any other clinical studies during the course of the study.
• Be capable and willing to give written informed consent to participate in the study.

Exclusion criteria

Exclusion criteria

To enroll in the clinical study, potential subjects must not:

• Have had three or more urinary tract infections (UTIs) in the past year from the date of consent.
• Have a UTI by urine culture, chlamydia, gonorrhea, or symptomatic yeast vaginitis or symptomatic bacterial vaginosis (BV) diagnosed by wet mount, or trichomoniasis, unless treated and proof of cure is documented within the screening period.
• Have used vaginal or systemic antibiotics or antifungals within 14 days prior to enrollment, with the exception of vaginal or systemic antibiotics or antifungals completed for the treatment of a UTI, BV, or yeast vaginitis diagnosed at screening within seven days of the Enrollment Visit.
• Have a history of any recurrent vaginal infections/disorders (either greater than or equal to four times in the past year or greater than or equal to three times in the previous six months from the date of consent).
• Be pregnant, have a suspected pregnancy, or desire to become pregnant during the course of the study.
• Have a history of diagnosed infertility or of conditions that may lead to infertility, without subsequent non-assisted reproductive technology intrauterine pregnancy.
• Have any maternal contraindications to pregnancy (medical condition) or chronic use of medications for which significant evidence of fetal risk exists.
• Have known or screen test positive for HIV infection.
• Have three or more outbreaks of genital herpes simplex virus (HSV) within the last year from the date of consent or be receiving suppressive therapy.
• Have visible genital condylomata (warts).
• Be lactating or breastfeeding.
• Have any clinically significant abnormal finding on physical examination including pelvic examination or baseline laboratory assessments which in the opinion of the Investigator, precludes study participation.
• Have clinically significant signs of vaginal or cervical irritation on pelvic examination.
• Be planning to have any (e.g., diagnostic or therapeutic) vaginal or cervical procedures during the period of the study.
• Have an abnormal Papanicolaou test (Pap test) based on the following criteria:

a. Pap test in the past 12 months from the date of screening with atypical squamous cells of undetermined significance (ASC-US) unless at least one of the following criteria is met: i. Less than 21 years of age. ii. A repeat Pap test at least six months later was normal. iii. Reflex human papillomavirus (HPV) testing was performed and was negative for high-risk HPV.

iv. 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.

b. Pap test in the past 12 months from the date of screening with low grade squamous intraepithelial lesion (LSIL) unless at least one of the following criteria is met: i. Less than 21 years of age. ii. 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.

c. Pap test in the past 12 months from the date of screening with atypical squamous cells in which high grade squamous intraepithelial lesion cannot be excluded (ASC-H), atypical glandular cells, high grade squamous intraepithelial lesion (HSIL), or ≥30 years old who are cytology negative and HPV 16- or HPV 18-positive 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.

d. Pap test in the past 12 months with malignant cells.

• Consume (on average) more than three drinks of an alcoholic beverage per day.
• In the opinion of the Investigator, have a history of substance abuse in the last 12 months.
• Have taken an investigational drug or used an investigational device within the past 30 days from the date of consent.
• In the opinion of the Investigator, have issues or concerns that may compromise the safety of the subject, impact the subject's compliance with the protocol requirements, or confound the reliability of the data acquired.
• Be an Evofem, PAREXEL, or clinical site employee regardless of direct involvement in research activities, or their close relative.