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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Uterine Fibroids

Intervention / Treatment
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* Drug: Proellex


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 47 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Proellex 12 mg PK group<br>Subjects receiving 12 mg Proellex administered vaginally, and completing a PK arm consisting of 1 x 24 hr PK of Proellex, 14 days of daily Proellex trough measurements, and 1 x 24 hr PK of Proellex after 14 days of daily dosing. 12 mg PK subjects will continue with the protocol as written after the first 2 week period and will be treated for a total of 16 weeks. | Drug: Proellex<br>* vaginal suppository, daily, for 12 weeks<br>* Other names: Telapristone acetate;|
| Experimental: Proellex 12 mg per protocol<br>Subjects receiving 12 mg Proellex daily, vaginally for 12 weeks | Drug: Proellex<br>* vaginal suppository, daily, for 12 weeks<br>* Other names: Telapristone acetate;|
| Experimental: Proellex 6 mg per protocol<br>Subjects receiving 6 mg Proellex daily, vaginally for 12 weeks | Drug: Proellex<br>* vaginal suppository, daily, for 12 weeks<br>* Other names: Telapristone acetate;|
| Experimental: Proellex 3 mg per protocol<br>Subjects will receive 3 mg Proellex daily, vaginally for 12 weeks. | Drug: Proellex<br>* vaginal suppository, daily, for 12 weeks<br>* Other names: Telapristone acetate;|
| Experimental: 24 mg Proellex<br>24 mg vaginal Proellex daily for 16 weeks | Drug: Proellex<br>* vaginal suppository, daily, for 12 weeks<br>* Other names: Telapristone acetate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Vaginal Bleeding | Change from baseline in vaginal bleeding assessed at the end of treatment (12 or 16 weeks) using a Pictorial Blood Loss Assessment Chart (PBAC), which measures volume (mL) of blood loss over a 28-day period Less blood loss represents an improvement. | 12 or 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Levels of Proellex | Determination of Cmax of Proellex at end of treatment | 12 or 16 weeks | 
| Uterine Fibroid Size | Percent change in volume of confirmed uterine fibroids at end of treatment, assessed by MRI | 12 or 16 weeks | 
| Induction of Amenorrhea at End of Treatment | Percentage of subjects with induced amenorrhea during last 28 days on drug Amenorrhea was deemed to be achieved if no daily bleeding score was greater than 1 during the last 28 calendar days of the dosing period. A score of 1 was to be indicated if spotting was observed which did not require a sanitary product. Subjects that terminated early were deemed not to have achieved amenorrhea. | End of treatment | 
| Endometrial Thickness | Percent change in median endometrial thickness from baseline to end of treatment assessed by ultrasound determination of uterine stripe. | 12 or 16 weeks | 
| Change in Quality of Life | Percentage change from baseline in median quality of life using uterine fibroid symptom and quality of life questionnaire (UFSQOL) | 12 or 16 weeks |