Evaluation of Safety, Pharmacokinetics, and Efficacy of Proellex Administered Vaginally in Women With Uterine Fibroids

A Phase 2, 3 Arm, Randomized, Double-Blind Study to Evaluate the Safety, PK and Efficacy of Proellex® Administered Vaginally in the Treatment of Premenopausal Women With Uterine Fibroids

To determine the safety, pharmacokinetics and efficacy of 4 doses (3, 6, 12, 24 mg) of Proellex in premenopausal women with uterine fibroids confirmed by ultrasound. Drug will be administered vaginally.

This study is a phase II, 5 arm study with a 12 week active dosing period. The study will be conducted in 2 stages. In the first stage, the first 6 women to be enrolled will be treated at the 12mg dose level, and in addition to the other required study assessments will be monitored with a 24-hour PK assessment on Day 14, and daily trough assessments for the first 14 days. If, at Visit 3, the Cmax or AUC of any subject treated at 12mg exceeds the mean observed for the highest safe oral dose administered in the ZP-204 study, all subjects enrolled at the 12mg level will be discontinued, no further patients will be treated at this dose level, and the 6mg vaginal dose will be assessed in a similar fashion. In the second stage, the remaining subjects will be randomized to a dose of 3, 6, 12 or 24 mg.

For all subjects there will be a 4-6 week placebo run-in period, to establish baseline parameters (bleeding and quality of life) followed by treatment at one of three single-blind Proellex doses (3, 6 or 12 mg daily, administered vaginally in capsule form.) The primary efficacy endpoint will be bleeding assessed using the Pictorial Blood Loss Assessment Chart (PBAC) after 12 or 16 weeks of treatment. The secondary endpoints will be changes in size of uterine fibroids assessed by MRI and improvement in quality of life assessed using the Uterine Fibroid Symptom and Health-Related Quality of Life questionnaire (UFSQOL0. Safety endpoints include significant adverse events, changes in physical examination results, and/or clinical laboratory results significantly outside of normal range. For subjects enrolled in Stage 2, PK will be assessed after the first and last doses and trough levels every 2 weeks.

Inclusion Criteria:

• Healthy adult females between 18 and 47 years of age with uterine fibroids confirmed by ultrasound.
• Normal transvaginal ultrasound (other than for presence of fibroids)
• History of menstrual events occurring in regular cycles
• Agreement not to attempt to become pregnant
• 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 subject diary
• Willing to discontinue hormonal contraceptives and consent to use of double barrier contraceptive techniques over the course of the study.
• Has a negative pregnancy test at the Screening and Baseline visits An exception for the pregnancy test requirement will be granted for subjects reporting surgical sterilization in medical history
• A Body Mass Index (BMI) between 18 and 39 inclusive
• Is available for all treatment and follow-up visits.

Exclusion Criteria:

• Subject is a 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
• Subject is pregnant or lactating or is attempting or expecting to become pregnant during the 6 month study period
• Women with abnormally high liver enzymes or liver disease. (ALT or AST exceeding 1.5xULN AND total bilirubin exceeding 1.5xULN at screening and confirmed on repeat).
• Received an investigational drug in the 30 days prior to the screening for this study
• Women with a history of PCOS
• Concurrent use of any testosterone, progestin, androgen, estrogen, anabolic steroids, DHEA or hormonal products for at least 2 weeks prior to screening and during the study.
• Use of oral contraceptives in the preceding 2 weeks. Use of Depo-Provera® in the preceding 6 months.
• Has an IUD in place
• Women currently using narcotics
• Women currently taking spironolactone
• Infectious disease screen is positive for HIV or Hepatitis A, B or C
• Clinically significant abnormal findings on screening examination 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