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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Repros Therapeutics Inc.
ClinicalTrials.gov Identifier:
NCT01451424
First received: October 11, 2011
Last updated: May 16, 2013
Last verified: May 2013
  Purpose

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


Condition Intervention Phase
Uterine Fibroids
Drug: telapristone acetate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: A Phase 2, Three-arm, Parallel Design, Randomized, Double-Blind Study to Evaluate the Safety, Pharmacokinetics and Efficacy of Proellex® (Telapristone Acetate) Administered Vaginally in the Treatment of Premenopausal Women With Uterine Fibroids Confirmed by Ultrasound

Further study details as provided by Repros Therapeutics Inc.:

Primary Outcome Measures:
  • Vaginal Bleeding [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Change in vaginal bleeding from baseline to 12 weeks of treatment


Secondary Outcome Measures:
  • Blood levels of Proellex [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Determination of blood levels of Proellex at baseline, 2 weeks (subset of 12 mg arm), and 12 weeks

  • Uterine fibroid size [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Change in size of confirmed uterine fibroids at baseline vs 12 weeks, assessed by MRI

  • Vaginal bleeding intensity [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Recorded number of days of vaginal bleeding and bleeding intensity at baseline vs 12 weeks.

  • Endometrial thickness [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Change in endometrial thickness from baseline to 12 weeks assessed by ultrasound.

  • Change in quality of life [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Change in quality of life using uterine fibroid symptom and quality of life questionnaire (UFSQOL)


Enrollment: 36
Study Start Date: February 2012
Study Completion Date: January 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Proellex 12 mg PK group
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.
Drug: telapristone acetate
vaginal suppository, daily, for 12 weeks
Other Name: Proellex
Experimental: Proellex 12 mg per protocol
Subjects receiving 12 mg Proellex daily, vaginally for 12 weeks
Drug: telapristone acetate
vaginal suppository, daily, for 12 weeks
Other Name: Proellex
Experimental: Proellex 6 mg per protocol
Subjects receiving 6 mg Proellex daily, vaginally for 12 weeks
Drug: telapristone acetate
vaginal suppository, daily, for 12 weeks
Other Name: Proellex
Experimental: Proellex 3 mg per protocol
Subjects will receiving 3 mg Proellex daily, vaginally for 12 weeks.
Drug: telapristone acetate
vaginal suppository, daily, for 12 weeks
Other Name: Proellex

Detailed Description:

This study is a phase II, 3 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 or 12 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 PBAC after 12 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 UFSQOL. 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.

  Eligibility

Ages Eligible for Study:   18 Years to 47 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01451424

Locations
United States, Florida
Miami Gardens, Florida, United States, 33169
United States, Texas
Houston, Texas, United States, 77030
Sponsors and Collaborators
Repros Therapeutics Inc.
Investigators
Study Director: Ronald D Wiehle, PhD Repros Therapeutics Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Repros Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT01451424     History of Changes
Other Study ID Numbers: ZPV-200
Study First Received: October 11, 2011
Last Updated: May 16, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leiomyoma
Myofibroma
Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Connective Tissue
Connective Tissue Diseases

ClinicalTrials.gov processed this record on August 19, 2014