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Determination of the Lowest, Safe and Effective Dose of Proellex

Sponsor
Repros Therapeutics Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01187043
Collaborator
(none)
52
Enrollment
1
Location
5
Arms
19
Duration (Months)
2.7
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
52 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Single (Participant)
Primary Purpose:
Treatment
Official Title:
A Single-Blind, Placebo Run-in, Phase I/II Study Comparing Five Oral Doses of Proellex®
Study Start Date :
Aug 1, 2010
Actual Primary Completion Date :
Mar 1, 2012
Actual Study Completion Date :
Mar 1, 2012

Arms and Interventions

Arm Intervention/Treatment
Experimental: ARM 1

1 mg Proellex

Drug: Proellex
1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5)
Other Names:
  • CDB-4124
  • Telapristone acetate

    		•
    Experimental: ARM 2

    3 mg Proellex

    Drug: Proellex
    1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5)
    Other Names:
  • CDB-4124
  • Telapristone acetate

    		•
    Experimental: ARM 3

    6 mg Proellex

    Drug: Proellex
    1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5)
    Other Names:
  • CDB-4124
  • Telapristone acetate

    		•
    Experimental: ARM 4

    9 mg Proellex

    Drug: Proellex
    1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5)
    Other Names:
  • CDB-4124
  • Telapristone acetate

    		•
    Experimental: ARM 5

    12 mg proellex

    Drug: Proellex
    1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5)
    Other Names:
  • CDB-4124
  • Telapristone acetate

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Induction Amenorrhea [10 weeks]

      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.

    Eligibility Criteria

    Criteria

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

    Locations

    Site City State Country Postal Code
    1 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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Repros Therapeutics Inc.
    ClinicalTrials.gov Identifier:
    NCT01187043
    Other Study ID Numbers:
    • ZP-204
    First Posted:
    Aug 23, 2010
    Last Update Posted:
    Jul 28, 2014
    Last Verified:
    Jun 1, 2014
    Keywords provided by Repros Therapeutics Inc.
    Liver Function
    Steady State Exposure
    Additional relevant MeSH terms:
    Amenorrhea

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title ARM 1 ARM 2 ARM 3 ARM 4 ARM 5
    Arm/Group Description 1 mg Proellex Proellex: 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5) 3 mg Proellex Proellex: 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5) 6 mg Proellex Proellex: 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5) 9 mg Proellex Proellex: 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5) 12 mg proellex Proellex: 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5)
    Period Title: Overall Study
    STARTED 12 10 12 12 12
    COMPLETED 11 10 8 12 10
    NOT COMPLETED 1 0 4 0 2

    Baseline Characteristics

    Arm/Group Title ARM 1 ARM 2 ARM 3 ARM 4 ARM 5 Total
    Arm/Group Description 1 mg Proellex Proellex: 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5) 3 mg Proellex Proellex: 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5) 6 mg Proellex Proellex: 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5) 9 mg Proellex Proellex: 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5) 12 mg proellex Proellex: 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5) Total of all reporting groups
    Overall Participants 12 10 12 12 12 58
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    37.4
    (7.8)
    38.5
    (7.6)
    37.1
    (8.6)
    34.4
    (8.3)
    36.3
    (7.0)
    36.7
    (7.8)
    Sex: Female, Male (Count of Participants)
    Female
    12
    100%
    10
    100%
    12
    100%
    12
    100%
    12
    100%
    58
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    12
    100%
    10
    100%
    12
    100%
    12
    100%
    12
    100%
    58
    100%

    Outcome Measures

    1. Primary Outcome
    Title Induction Amenorrhea
    Description 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.
    Time Frame 10 weeks

    Outcome Measure Data

    Analysis Population Description
    Per protocol: subjects who exhibited trough levels of proellex on at least 7 of the 10 weekly visits during the dosing period
    Arm/Group Title ARM 1 ARM 2 ARM 3 ARM 4 ARM 5
    Arm/Group Description 1 mg Proellex Proellex: 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5) 3 mg Proellex Proellex: 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5) 6 mg Proellex Proellex: 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5) 9 mg Proellex Proellex: 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5) 12 mg proellex Proellex: 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5)
    Measure Participants 2 9 7 10 7
    Number [participants]
    2
    16.7%
    9
    90%
    6
    50%
    8
    66.7%
    6
    50%

    Adverse Events

    Time Frame From first dose to one week post dosing (about 11 weeks).
    Adverse Event Reporting Description
    Arm/Group Title ARM 1 ARM 2 ARM 3 ARM 4 ARM 5
    Arm/Group Description 1 mg Proellex Proellex: 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5) 3 mg Proellex Proellex: 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5) 6 mg Proellex Proellex: 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5) 9 mg Proellex Proellex: 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5) 12 mg proellex Proellex: 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5)
    All Cause Mortality
    ARM 1 ARM 2 ARM 3 ARM 4 ARM 5
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    ARM 1 ARM 2 ARM 3 ARM 4 ARM 5
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/12 (0%) 0/10 (0%) 1/12 (8.3%) 0/12 (0%) 0/12 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer 0/12 (0%) 0 0/10 (0%) 0 1/12 (8.3%) 1 0/12 (0%) 0 0/12 (0%) 0
    Other (Not Including Serious) Adverse Events
    ARM 1 ARM 2 ARM 3 ARM 4 ARM 5
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 8/12 (66.7%) 6/10 (60%) 7/12 (58.3%) 11/12 (91.7%) 11/12 (91.7%)
    Ear and labyrinth disorders
    Right ear ache 0/12 (0%) 0 1/10 (10%) 1 0/12 (0%) 0 0/12 (0%) 0 0/12 (0%) 0
    Gastrointestinal disorders
    Abdominal cramps 1/12 (8.3%) 1 1/10 (10%) 1 0/12 (0%) 0 0/12 (0%) 0 0/12 (0%) 0
    Abdominal discomfort 1/12 (8.3%) 1 0/10 (0%) 0 0/12 (0%) 0 0/12 (0%) 0 0/12 (0%) 0
    Abdominal pain 0/12 (0%) 0 0/10 (0%) 0 0/12 (0%) 0 1/12 (8.3%) 1 1/12 (8.3%) 1
    Constipation 0/12 (0%) 0 1/10 (10%) 1 0/12 (0%) 0 0/12 (0%) 0 0/12 (0%) 0
    Diarrhea 0/12 (0%) 0 0/10 (0%) 0 0/12 (0%) 0 1/12 (8.3%) 1 0/12 (0%) 0
    Emesis 0/12 (0%) 0 0/10 (0%) 0 2/12 (16.7%) 2 1/12 (8.3%) 1 0/12 (0%) 0
    Nausea 2/12 (16.7%) 2 0/10 (0%) 0 2/12 (16.7%) 2 1/12 (8.3%) 1 1/12 (8.3%) 2
    General disorders
    Fatigue 0/12 (0%) 0 0/10 (0%) 0 0/12 (0%) 0 1/12 (8.3%) 1 0/12 (0%) 0
    Facial pain 0/12 (0%) 0 0/10 (0%) 0 0/12 (0%) 0 0/12 (0%) 0 1/12 (8.3%) 1
    Infections and infestations
    Gastroenteritis 0/12 (0%) 0 0/10 (0%) 0 0/12 (0%) 0 2/12 (16.7%) 2 0/12 (0%) 0
    Pelvic inflammatory disease 0/12 (0%) 0 0/10 (0%) 0 1/12 (8.3%) 1 0/12 (0%) 0 0/12 (0%) 0
    Pustule 0/12 (0%) 0 0/10 (0%) 0 0/12 (0%) 0 1/12 (8.3%) 1 0/12 (0%) 0
    Tooth abcess 1/12 (8.3%) 1 0/10 (0%) 0 0/12 (0%) 0 0/12 (0%) 0 0/12 (0%) 0
    URI 1/12 (8.3%) 2 1/10 (10%) 1 0/12 (0%) 0 2/12 (16.7%) 2 1/12 (8.3%) 1
    UTI 0/12 (0%) 0 0/10 (0%) 0 1/12 (8.3%) 1 0/12 (0%) 0 0/12 (0%) 0
    Viral gastroenteritis 0/12 (0%) 0 0/10 (0%) 0 0/12 (0%) 0 0/12 (0%) 0 1/12 (8.3%) 1
    Injury, poisoning and procedural complications
    Insect bite 1/12 (8.3%) 1 0/10 (0%) 0 0/12 (0%) 0 0/12 (0%) 0 0/12 (0%) 0
    Laceration 0/12 (0%) 0 0/10 (0%) 0 0/12 (0%) 0 2/12 (16.7%) 2 0/12 (0%) 0
    Ankle sprain 0/12 (0%) 0 0/10 (0%) 0 0/12 (0%) 0 0/12 (0%) 0 1/12 (8.3%) 1
    Abrasion 0/12 (0%) 0 0/10 (0%) 0 0/12 (0%) 0 1/12 (8.3%) 1 0/12 (0%) 0
    Investigations
    Abnormal PAP smear 0/12 (0%) 0 0/10 (0%) 0 0/12 (0%) 0 1/12 (8.3%) 1 0/12 (0%) 0
    Weight gain 0/12 (0%) 0 0/10 (0%) 0 0/12 (0%) 0 0/12 (0%) 0 1/12 (8.3%) 1
    Metabolism and nutrition disorders
    Decreased appetite 0/12 (0%) 0 0/10 (0%) 0 0/12 (0%) 0 1/12 (8.3%) 1 0/12 (0%) 0
    Musculoskeletal and connective tissue disorders
    Lower back pain 1/12 (8.3%) 1 0/10 (0%) 0 0/12 (0%) 0 0/12 (0%) 0 0/12 (0%) 0
    Muscle pain 0/12 (0%) 0 0/10 (0%) 0 0/12 (0%) 0 0/12 (0%) 0 1/12 (8.3%) 1
    Muscle spasm 0/12 (0%) 0 0/10 (0%) 0 0/12 (0%) 0 0/12 (0%) 0 1/12 (8.3%) 1
    Back pain 0/12 (0%) 0 0/10 (0%) 0 1/12 (8.3%) 1 0/12 (0%) 0 0/12 (0%) 0
    Elbow pain 1/12 (8.3%) 1 0/10 (0%) 0 0/12 (0%) 0 1/12 (8.3%) 1 0/12 (0%) 0
    Arm pain 0/12 (0%) 0 0/10 (0%) 0 0/12 (0%) 0 1/12 (8.3%) 1 0/12 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer 0/12 (0%) 0 0/10 (0%) 0 1/12 (8.3%) 1 0/12 (0%) 0 0/12 (0%) 0
    Nervous system disorders
    Dizziness 2/12 (16.7%) 2 0/10 (0%) 0 0/12 (0%) 0 2/12 (16.7%) 2 0/12 (0%) 0
    Headache 1/12 (8.3%) 1 1/10 (10%) 1 1/12 (8.3%) 1 1/12 (8.3%) 1 4/12 (33.3%) 4
    Optic neuritis 0/12 (0%) 0 0/10 (0%) 0 1/12 (8.3%) 1 0/12 (0%) 0 0/12 (0%) 0
    Vasovagal episode 1/12 (8.3%) 1 0/10 (0%) 0 1/12 (8.3%) 1 1/12 (8.3%) 1 0/12 (0%) 0
    Reproductive system and breast disorders
    Breast tenderness 0/12 (0%) 0 1/10 (10%) 1 1/12 (8.3%) 1 0/12 (0%) 0 0/12 (0%) 0
    Endometrial hyperplasia 0/12 (0%) 0 1/10 (10%) 1 0/12 (0%) 0 0/12 (0%) 0 0/12 (0%) 0
    Irregular menses 0/12 (0%) 0 1/10 (10%) 1 0/12 (0%) 0 0/12 (0%) 0 0/12 (0%) 0
    Menorrhagia 0/12 (0%) 0 1/10 (10%) 1 0/12 (0%) 0 2/12 (16.7%) 2 0/12 (0%) 0
    Menstrual cramps 0/12 (0%) 0/10 (0%) 0/12 (0%) 1/12 (8.3%) 0/12 (0%)
    Mittelschmertz 0/12 (0%) 1/10 (10%) 0/12 (0%) 1/12 (8.3%) 1/12 (8.3%)
    Vaginal discharge 0/12 (0%) 1/10 (10%) 0/12 (0%) 1/12 (8.3%) 1/12 (8.3%)
    Yeast infection 0/12 (0%) 0/10 (0%) 0/12 (0%) 1/12 (8.3%) 0/12 (0%)
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis 1/12 (8.3%) 1/10 (10%) 0/12 (0%) 0/12 (0%) 0/12 (0%)
    Cough 0/12 (0%) 1/10 (10%) 0/12 (0%) 0/12 (0%) 0/12 (0%)
    Rhinitis 0/12 (0%) 0/10 (0%) 1/12 (8.3%) 0/12 (0%) 0/12 (0%)
    Skin and subcutaneous tissue disorders
    Acne 1/12 (8.3%) 1 0/10 (0%) 0 0/12 (0%) 0 1/12 (8.3%) 1 0/12 (0%) 0
    Benign breast lesion 0/12 (0%) 0/10 (0%) 1/12 (8.3%) 0/12 (0%) 0/12 (0%)
    Contact dermatitis 1/12 (8.3%) 0/10 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%)
    Ecchymosis 0/12 (0%) 0/10 (0%) 0/12 (0%) 0/12 (0%) 1/12 (8.3%)
    Hair loss 1/12 (8.3%) 0/10 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%)
    Rash 0/12 (0%) 0/10 (0%) 0/12 (0%) 1/12 (8.3%) 0/12 (0%)
    Vascular disorders
    Hot flashes 1/12 (8.3%) 0/10 (0%) 0/12 (0%) 2/12 (16.7%) 3/12 (25%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Prior to publication, Investigator shall submit to the Sponsor a copy of any proposed publication. Sponsor shall have sixty (60) days to review the proposed publication for possible disclosure of Sponsor's Confidential Information and, upon request of Sponsor, Investigator shall delete any of Sponsor's Confidential Information or withhold submission of such publication to allow Sponsor to protect its intellectual property rights

    Results Point of Contact

    Name/Title Jennifer L. Wike
    Organization Repros Therapeutics Inc.
    Phone 281-719-3402
    Email jwike@reprosrx.com
    Responsible Party:
    Repros Therapeutics Inc.
    ClinicalTrials.gov Identifier:
    NCT01187043
    Other Study ID Numbers:
    • ZP-204
    First Posted:
    Aug 23, 2010
    Last Update Posted:
    Jul 28, 2014
    Last Verified:
    Jun 1, 2014