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

Uterine Fibroids Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01451424
• Other study ID #: ZPV-200
• Status: Completed
• Phase: Phase 2
• First received: October 11, 2011
• Last updated: August 8, 2014
• Start date: February 2012
• Est. completion date: January 2013

Study information

• Verified date: August 2014
• Source: Repros Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: January 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 47 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leiomyoma
• Uterine Fibroids

Intervention

Drug:
• Proellex
vaginal suppository, daily, for 12 weeks

Locations

Country	Name	City	State
United States	Advances in Health	Houston	Texas
United States	Cetero Research	Miami Gardens	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Repros Therapeutics Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	12 or 16 weeks	No
Secondary	Blood Levels of Proellex	Determination of Cmax of Proellex at end of treatment	12 or 16 weeks	No
Secondary	Uterine Fibroid Size	Percent change in volume of confirmed uterine fibroids at end of treatment, assessed by MRI	12 or 16 weeks	No
Secondary	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.	End of treatment	No
Secondary	Endometrial Thickness	Percent change in median endometrial thickness from baseline to end of treatment assessed by ultrasound determination of uterine stripe.	12 or 16 weeks	Yes
Secondary	Change in Quality of Life	Percentage change from baseline in median quality of life using uterine fibroid symptom and quality of life questionnaire (UFSQOL)	12 or 16 weeks	No

External Links

•   Repros Therapeutics Inc corporate website