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

Primary Purpose

Uterine Fibroids

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Proellex
Sponsored by
Repros Therapeutics Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Uterine Fibroids

Eligibility Criteria

18 Years - 47 Years (Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Cetero Research
  • Advances in Health

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Proellex 12 mg PK group

Proellex 12 mg per protocol

Proellex 6 mg per protocol

Proellex 3 mg per protocol

24 mg Proellex

Arm Description

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.

Subjects receiving 12 mg Proellex daily, vaginally for 12 weeks

Subjects receiving 6 mg Proellex daily, vaginally for 12 weeks

Subjects will receive 3 mg Proellex daily, vaginally for 12 weeks.

24 mg vaginal Proellex daily for 16 weeks

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Blood Levels of Proellex
Determination of Cmax of Proellex at end of treatment
Uterine Fibroid Size
Percent change in volume of confirmed uterine fibroids at end of treatment, assessed by MRI
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.
Endometrial Thickness
Percent change in median endometrial thickness from baseline to end of treatment assessed by ultrasound determination of uterine stripe.
Change in Quality of Life
Percentage change from baseline in median quality of life using uterine fibroid symptom and quality of life questionnaire (UFSQOL)

Full Information

First Posted
October 11, 2011
Last Updated
August 8, 2014
Sponsor
Repros Therapeutics Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01451424
Brief Title
Evaluation of Safety, Pharmacokinetics, and Efficacy of Proellex Administered Vaginally in Women With Uterine Fibroids
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2014
Overall Recruitment Status
Completed
Study Start Date
February 2012 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
January 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Repros Therapeutics Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Uterine Fibroids

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Proellex 12 mg PK group
Arm Type
Experimental
Arm Description
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.
Arm Title
Proellex 12 mg per protocol
Arm Type
Experimental
Arm Description
Subjects receiving 12 mg Proellex daily, vaginally for 12 weeks
Arm Title
Proellex 6 mg per protocol
Arm Type
Experimental
Arm Description
Subjects receiving 6 mg Proellex daily, vaginally for 12 weeks
Arm Title
Proellex 3 mg per protocol
Arm Type
Experimental
Arm Description
Subjects will receive 3 mg Proellex daily, vaginally for 12 weeks.
Arm Title
24 mg Proellex
Arm Type
Experimental
Arm Description
24 mg vaginal Proellex daily for 16 weeks
Intervention Type
Drug
Intervention Name(s)
Proellex
Other Intervention Name(s)
Telapristone acetate
Intervention Description
vaginal suppository, daily, for 12 weeks
Primary Outcome Measure Information:
Title
Change From Baseline in Vaginal Bleeding
Description
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.
Time Frame
12 or 16 weeks
Secondary Outcome Measure Information:
Title
Blood Levels of Proellex
Description
Determination of Cmax of Proellex at end of treatment
Time Frame
12 or 16 weeks
Title
Uterine Fibroid Size
Description
Percent change in volume of confirmed uterine fibroids at end of treatment, assessed by MRI
Time Frame
12 or 16 weeks
Title
Induction of Amenorrhea at End of Treatment
Description
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.
Time Frame
End of treatment
Title
Endometrial Thickness
Description
Percent change in median endometrial thickness from baseline to end of treatment assessed by ultrasound determination of uterine stripe.
Time Frame
12 or 16 weeks
Title
Change in Quality of Life
Description
Percentage change from baseline in median quality of life using uterine fibroid symptom and quality of life questionnaire (UFSQOL)
Time Frame
12 or 16 weeks

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
47 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ronald D Wiehle, PhD
Organizational Affiliation
Repros Therapeutics Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Cetero Research
City
Miami Gardens
State/Province
Florida
ZIP/Postal Code
33169
Country
United States
Facility Name
Advances in Health
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.reprosrx.com
Description
Repros Therapeutics Inc corporate website

Learn more about this trial

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

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