Determination of the Lowest, Safe and Effective Dose of Proellex

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the effects of five different doses of Proellex on menses, ovulation, liver function, and steady state exposure in women of reproductive age.

Detailed Description
-----------------
A phase I/II, 5 arm, single blind study, comparing five doses of Proellex to matching placebo in healthy adult female subjects of reproductive age. Exposure to study drug will be for up to 10 weeks. In-clinic pharmacokinetic (PK) assessments will be made on the first day of dosing and on the last day (week 10). Office visits will occur every week to assess liver function and trough blood concentrations for Proellex and primary metabolite. Daily vaginal bleeding diaries will be maintained during the course of the study. A single blind run-in period of up to 56 days will begin the study to assess baseline menstrual patterns will be utilized. Twelve subjects per treatment group (total 60 subjects) will be assigned to each dose. New groups will not begin dosing until the previous dose group has completed. Daily treatments will be either 1 mg, 3 mg, 6 mg, 9 mg, 12 mg Proellex. A single blind run-in period using placebo will be incorporated to establish baseline parameters.

Official Title
-----------------
A Single-Blind, Placebo Run-in, Phase I/II Study Comparing Five Oral Doses of Proellex®

Conditions
-----------------
Amenorrhea

Intervention / Treatment
-----------------
* Drug: Proellex


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Ability to understand and provide a written informed consent. Healthy adult females between 18 and 50 years of age. Included in this group are women with the following conditions, not currently receiving drug treatment: Excessive menstrual bleeding; Menstrual pain; Confirmed uterine fibroids; and Confirmed endometriosis Normal menstrual cycle of 26-32 days Agree not to attempt to become pregnant Agree to limit alcohol consumption to no more than 2 drinks per week and to avoid alcohol consumption within 48 hours of each visit Ability to swallow gelatin capsules 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 7 month study period Women with abnormal liver enzymes or liver disease. Subject previously participated in Proellex clinical trials: ZPE-201, ZPU-003, ZPU-301, ZPU-302, ZPU-303, ZPU-304, ZPU-305, and ZPU-307. 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 or hormone releasing IUDs in the preceding 30 days. Use of Depo-Provera® in the preceding 6 months. Women currently using narcotics Women currently taking cimetidine or spironolactone 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
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARM 1<br>1 mg Proellex | Drug: Proellex<br>* 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5)<br>* Other names: Telapristone acetate;|
| Experimental: ARM 2<br>3 mg Proellex | Drug: Proellex<br>* 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5)<br>* Other names: Telapristone acetate;|
| Experimental: ARM 3<br>6 mg Proellex | Drug: Proellex<br>* 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5)<br>* Other names: Telapristone acetate;|
| Experimental: ARM 4<br>9 mg Proellex | Drug: Proellex<br>* 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5)<br>* Other names: Telapristone acetate;|
| Experimental: ARM 5<br>12 mg proellex | Drug: Proellex<br>* 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5)<br>* Other names: Telapristone acetate;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Induction Amenorrhea | Induction of amenorrhea as determined by suppression of ovulation and/or menses, measured by using ovulation timing kits and daily diary for bleeding. Five doses will be compared in an escalating-dose, to independent groups, to a run-in placebo treatment period. | 10 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Liver Function, Steady State Exposure