Determination of the Lowest, Safe and Effective Dose of the Anti-Progestin, Proellex, in Healthy Women - Full Text View

Purpose

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.

Condition	Intervention	Phase
Amenorrhea	Drug: Telapristone Acetate	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Single Blind (Subject) Primary Purpose: Treatment
Official Title:	An Escalating Dose, Single-Blind, Placebo Run-in, Phase I/II Study in Healthy Women, Comparing Five Oral Doses of the Anti-progestin, Proellex® (Telapristone Acetate, CDB-4124), Impact on Induction of Amenorrhea, Liver Function, and Assessment of Steady State Exposure

Further study details as provided by Repros Therapeutics Inc.:

Primary Outcome Measures:

Induction amenorrhea [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
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.
Affected liver function [ Time Frame: weekly ] [ Designated as safety issue: Yes ]
Determine if any signal for liver toxicity can be detected after 8 weeks of dosing at any dose

Enrollment:	52
Study Start Date:	August 2010
Study Completion Date:	March 2012
Primary Completion Date:	March 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: ARM 1 1 mg	Drug: Telapristone Acetate 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5) Other Names: Proellex CDB-4124
Experimental: ARM 2 3 mg	Drug: Telapristone Acetate 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5) Other Names: Proellex CDB-4124
Experimental: ARM 3 6 mg	Drug: Telapristone Acetate 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5) Other Names: Proellex CDB-4124
Experimental: ARM 4 9 mg	Drug: Telapristone Acetate 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5) Other Names: Proellex CDB-4124
Experimental: ARM 5 12 mg	Drug: Telapristone Acetate 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5) Other Names: Proellex CDB-4124

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.

Eligibility

Ages Eligible for Study:	18 Years to 50 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01187043

Locations

United States, Texas
ICON Devlopment Solutions
San Antonio, Texas, United States, 78209

Sponsors and Collaborators

Repros Therapeutics Inc.

Investigators

Principal Investigator:

Laura M Sterling, MD

ICON Development Solutions

More Information

No publications provided

Responsible Party:	Repros Therapeutics Inc.
ClinicalTrials.gov Identifier:	NCT01187043 History of Changes
Other Study ID Numbers:	ZP-204
Study First Received:	August 20, 2010
Last Updated:	May 16, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Repros Therapeutics Inc.:

Liver Function
Steady State Exposure

Additional relevant MeSH terms:

Amenorrhea
Menstruation Disturbances
Pathologic Processes
Progestins

Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 17, 2013