Safety and Efficacy of Telapristone Acetate (Proellex®) in the Treatment of Pre-Menopausal Women With Confirmed, Symptomatic Endometriosis

A Phase 2, Multi-Center, Three-Arm, Parallel Design, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of 6 and 12 mg Proellex® (Telapristone Acetate) Administered Orally in the Treatment of Premenopausal Women With Confirmed Symptomatic Endometriosis

The primary purpose of this study is to determine the safety and efficacy of two oral doses of telapristone acetate administered to premenopausal women with pelvic pain associated with endometriosis confirmed within the last seven years and using prescription analgesics for symptomatic pain.

This study is a phase 2, 3-arm-study with an 18-week active dosing period and an option for participants to receive 2 additional 16-week cycles of active treatment at their randomized dose [6 mg or 12 mg/day]. Placebo participants who elect additional treatment will receive treatment at 12 mg/day. The treatment dose will remain double-blind. The study will be conducted in 3 stages. The first stage is a no treatment baseline assessment period. This stage will last as long as it takes to record at least one full menstrual cycle (ovulation until ovulation).

For stage 2, following the run-in stage, at Visit 3, 60 participants will be randomized into one of 3 arms in a 1-1-1 fashion. The start of dosing should commence as soon as possible after ovulation following the end of the previous menstrual event.

For stage 3, participants who are eligible to receive additional cycles of treatment and who elect to continue treatment will be scheduled within a week before the second expected menses (+/- 2 days), following the off-drug interval. Participants will receive 2 cycles of treatment separated by an off-drug interval (ODI), after which they will be followed until menses has returned.

Inclusion Criteria:

• Adult females between 18 and 47 years of age using prescription analgesics for endometriosis pain and with a Biberoglu Behrman Symptom Severity Scale (BBSS) score ≥7 at screening (assessed over the previous 28 days).
• Endometriosis diagnosis must have been surgically confirmed within 7 years. A laparoscopic diagnosis is acceptable.
• Participants must have a history of at least 3 regular menstrual cycles in which symptoms of endometriosis occurred immediately prior to screening.
• Normal or abnormal but non-clinically significant transvaginal ultrasound.
• History of menstrual events occurring in regular cycles.
• Agreement not to attempt to become pregnant during the trial.
• Agreement to limit alcohol consumption to no more than 2 drinks per week and to avoid alcohol consumption within 48 hours before each visit.
• Ability to complete a daily electronic participant diary and study procedures in compliance with the protocol.
• Women of child-bearing potential must be willing to use double-barrier contraception during the study and for 30 days after discontinuation of study medication. Acceptable double-barrier methods are: male condom with spermicide; male condom with diaphragm; diaphragm containing spermicide plus additional intra-vaginal spermicide.
• Has a negative pregnancy test at the Screening and Baseline visits, and subsequent study visits.
• A Body Mass Index (BMI) between 18 and 39 inclusive.
• Is available for all treatment and follow-up visits.

Exclusion Criteria:

• Post-menopausal woman, defined as either; six (6) months or more (immediately prior to screening visit) without a menstrual period, or prior hysterectomy and/or oophorectomy.
• Pregnant or lactating or is attempting or expecting to become pregnant during the 6-7 month study period.
• Women with abnormally high liver enzymes or liver disease [alanine transaminase (ALT) or aspartate aminotransferase (AST) exceeding 2 x upper limit of normal (ULN) and total bilirubin exceeding 1.5 x ULN at screening and confirmed on repeat].
• Received an investigational drug in the 30 days prior to the screening for this study.
• History of polycystic ovary syndrome (PCOS).
• Concurrent use of any testosterone, androgen, anabolic steroids, dehydroepiandrosterone (DHEA) or hormonal products for at least 2 weeks prior to screening and during the study. Oral contraceptive use for control of endometriosis symptoms is acceptable for the first 28-days of the study.
• Use of Depo-Provera® in the preceding 6 months.
• Use of Gonadotrophin releasing hormone (GnRH) as (e.g. Lupron Depot) within 3 months of the first dose of study drug (Lupron Depot must have a wash-out period of 3 months after the period of duration of the Lupron dose).
• Has an intrauterine device (IUD) in place. Copper IUDs (non-hormone containing will be permitted).
• Presence of intramural fibroids that impact the endometrial stripe, submucosal fibroids (any size), or endometrial polyps. Subserosal and intramural fibroids with no impact on the endometrial stripe are acceptable.
• Presence of endometrioma(s).
• Present history or condition that causes non-endometriosis related dyspareunia (e.g. vulvar vestibulitis).
• Past or present history of thrombophlebitis or thromboembolic disorders.
• Known or suspected carcinoma of the breast or reproductive organs.
• History of abnormal electrocardiogram (ECG) that, in the opinion of the investigator, is clinically significant and will prevent the participant from completing the study, including a QTc (corrected QT interval) of greater than 450 milliseconds (ms).
• Cervical dysplasia classified as Atypical Squamous Cells of Undetermined Significance (ASCUS) associated with high-risk human papilloma virus (HPV) or Low/High Grade Squamous Intraepithelial Lesion (LGSIL or HGSIL).
• History of abnormal endometrial biopsy including the presence of Endometrial Intraepithelial Neoplasia (EIN).
• Recent history (within past 6 months) of alcoholism or drug abuse.
• Known active infection with Human Immunodeficiency Virus (HIV), Hepatitis A, B or C.
• Previous history of auto-immune disease and/or positive antinuclear antigen (ANA).
• Endometrial stripe ≥18 mm in thickness at Visit 1.
• Women currently taking cimetidine or spironolactone.
• Clinically significant abnormal findings on screening examination and laboratory assessments or any condition which in the opinion of the investigator would interfere with the participant's ability to comply with the study instructions or endanger the participant if she took part in the study.