Safety and Efficacy of Telapristone Acetate (Proellex®) in the Treatment of Pre-Menopausal Women With Confirmed, Symptomatic Endometriosis

NCT01728454 | Completed Phase 2 Results DMC

• 1 other identifier: ZPE-202
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 10

Brief Summary

The primary purpose of this study is to determine the safety and efficacy of two oral doses of telapristone acetate administered to premenopausal women with pelvic pain associated with endometriosis confirmed within the last seven years and using prescription analgesics for symptomatic pain.

Conditions

Endometriosis

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in Individual Biberoglu Behrman Symptom Severity Scale (BBSS) Score for Dysmenorrhea

  The BBSS scale defined dysmenorrhea according to the loss of work efficiency and need for bed rest. The dysmenorrhea was graded on a scale from 0 to 3 where, 0 = None; 1 = Mild (some loss in work efficiency); 2 = Moderate (in bed part of the day, occasional loss of work efficiency); 3 = Severe (in bed one or more days, incapacitation), with higher scores indicating more severe symptoms. Participants were provided with a daily diary to record information about participant-reported scores for endometriosis pain each day. Daily scores were standardized to a 28-day period for each interval (Baseline, On-drug Cycle 1 and Off-drug Cycle 1) calculated as the sum of scores in the interval divided by the number of the days in the interval multiplied by 28. A negative change from Baseline indicates improvement.

  Baseline (28-day Baseline Menstrual Cycle) to the last day of dosing in Cycle 1 (On-drug Cycle 1 is 18 weeks) and at the end of Off-drug Cycle 1 (Off-drug Cycle 1 is 3 weeks following On-drug Cycle 1)

• Change From Baseline in Individual BBSS Score for Dyspareunia

  The BBSS scale defined deep dyspareunia according to the limitation of sexual activity. The dyspareunia was graded on a scale from 0 to 3 where, 0= None (no discomfort); 1= Mild (tolerated discomfort); 2= Moderate (intercourse painful to the point of interruption); 3= Severe (intercourse avoided because of pain), with higher scores indicating more severe symptoms. Participants were provided with a daily diary to record information about participant-reported scores for endometriosis pain each day. Daily scores were standardized to a 28-day period for each interval (Baseline, On-drug Cycle 1 and Off-drug Cycle 1) calculated as the sum of scores in the interval divided by the number of the days in the interval multiplied by 28. A negative change from Baseline indicates improvement..

  Baseline (28-day Baseline Menstrual Cycle) to the last day of dosing in Cycle 1 (On-drug Cycle 1 is 18 weeks) and at the end of Off-drug Cycle 1 (Off-drug Cycle 1 is 3 weeks following On-drug Cycle 1)

• Change From Baseline in Individual BBSS Score for Non-Menstrual Pelvic Pain

  The BBSS scale defined non-menstrual pelvic pain according to various degrees of discomfort and use of analgesics. The non-menstrual pelvic pain was graded on a scale from 0 to 3 where, 0= None (absence of pain); 1= Mild (occasional pelvic discomfort); 2= Moderate (noticeable discomfort for most of the cycle); 3= Severe (pain persisting during the cycle or requiring strong analgesics), with higher scores indicating more severe symptoms. Participants were provided with a daily diary to record information about participant-reported scores for endometriosis pain each day. Daily scores were standardized to a 28-day period for each interval (Baseline, On-drug Cycle 1 and Off-drug Cycle 1) calculated as the sum of scores in the interval divided by the number of the days in the interval multiplied by 28. A negative change from Baseline indicates improvement.

  Baseline (28-day Baseline Menstrual Cycle) to the last day dosing in Cycle 1 (On-drug Cycle 1 is 18 weeks) and to the end of Off-drug Cycle 1 (Off-drug Cycle 1 is 3 weeks following On-drug Cycle 1)

Secondary Outcomes (9)

• Change From Baseline in Prescription Analgesics Usage

  Baseline (28-day Baseline Menstrual Cycle) to the last day of dosing in Cycle 1 (On-drug Cycle 1 is 18 weeks)

• Percentage Change From Baseline in Prescription Analgesics Usage

  Baseline (28-day Baseline Menstrual Cycle) to last 28 days of dosing in Cycle 1 (On-drug Cycle 1 is 18 weeks)

• Change From Baseline in Non-Prescription Analgesics Usage

  Baseline (28-day Baseline Menstrual Cycle) to last day of dosing in Cycle 1 (On-drug Cycle 1 is 18 weeks)

• Percentage Change From Baseline in Non-Prescription Analgesics Usage

  Baseline (28-day Baseline Menstrual Cycle) to last 28 days of dosing in Cycle 1 (On-drug Cycle 1 is 18 weeks)

• Change From Baseline in Total Analgesics Usage

  Baseline (28-day Baseline Menstrual Cycle) to last day of dosing in Cycle 1 (On-drug Cycle 1 is 18 weeks)

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Following the Stage 1 no treatment baseline assessment period, placebo matching capsules, orally, once daily for 18 weeks in Stage 2. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 12 milligrams (mg)/day separated by an off-drug interval (ODI) in Stage 3.

Drug: Placebo

Telapristone acetate 6 mg

EXPERIMENTAL

Following the Stage 1 no treatment baseline assessment period, telapristone acetate (Proellex®) 6 mg capsules, orally once daily for 18 weeks in Stage 2. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 6 mg/day separated by an ODI in Stage 3.

Drug: Telapristone acetate

Telapristone acetate 12 mg

EXPERIMENTAL

Following the Stage 1 no treatment baseline assessment period, telapristone acetate (Proellex®) 12 mg capsules, orally once daily for 18 weeks. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 12 mg/day separated by an ODI in Stage 3.

Drug: Telapristone acetate

Interventions

Placebo DRUG

Placebo matching capsules, orally, once daily for 18 weeks.

Placebo

Telapristone acetate DRUG

Telapristone acetate capsules, orally once daily for 18 weeks.

Also known as: Proellex®

Telapristone acetate 12 mg; Telapristone acetate 6 mg

Eligibility Criteria

• Age: 18 Years - 47 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adult females between 18 and 47 years of age using prescription analgesics for endometriosis pain and with a Biberoglu Behrman Symptom Severity Scale (BBSS) score ≥7 at screening (assessed over the previous 28 days).
• Endometriosis diagnosis must have been surgically confirmed within 7 years. A laparoscopic diagnosis is acceptable.
• Participants must have a history of at least 3 regular menstrual cycles in which symptoms of endometriosis occurred immediately prior to screening.
• Normal or abnormal but non-clinically significant transvaginal ultrasound.
• History of menstrual events occurring in regular cycles.
• Agreement not to attempt to become pregnant during the trial.
• 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 electronic participant diary and study procedures in compliance with the protocol.
• Women of child-bearing potential must be willing to use double-barrier contraception during the study and for 30 days after discontinuation of study medication. Acceptable double-barrier methods are: male condom with spermicide; male condom with diaphragm; diaphragm containing spermicide plus additional intra-vaginal spermicide.
• Has a negative pregnancy test at the Screening and Baseline visits, and subsequent study visits.
• A Body Mass Index (BMI) between 18 and 39 inclusive.
• Is available for all treatment and follow-up visits.

You may not qualify if:

• 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.
• Pregnant or lactating or is attempting or expecting to become pregnant during the 6-7 month study period.
• Women with abnormally high liver enzymes or liver disease \[alanine transaminase (ALT) or aspartate aminotransferase (AST) exceeding 2 x upper limit of normal (ULN) and total bilirubin exceeding 1.5 x ULN at screening and confirmed on repeat\].
• Received an investigational drug in the 30 days prior to the screening for this study.
• History of polycystic ovary syndrome (PCOS).
• Concurrent use of any testosterone, androgen, anabolic steroids, dehydroepiandrosterone (DHEA) or hormonal products for at least 2 weeks prior to screening and during the study. Oral contraceptive use for control of endometriosis symptoms is acceptable for the first 28-days of the study.
• Use of Depo-Provera® in the preceding 6 months.
• Use of Gonadotrophin releasing hormone (GnRH) as (e.g. Lupron Depot) within 3 months of the first dose of study drug (Lupron Depot must have a wash-out period of 3 months after the period of duration of the Lupron dose).
• Has an intrauterine device (IUD) in place. Copper IUDs (non-hormone containing will be permitted).
• Presence of intramural fibroids that impact the endometrial stripe, submucosal fibroids (any size), or endometrial polyps. Subserosal and intramural fibroids with no impact on the endometrial stripe are acceptable.
• Presence of endometrioma(s).
• Present history or condition that causes non-endometriosis related dyspareunia (e.g. vulvar vestibulitis).
• Past or present history of thrombophlebitis or thromboembolic disorders.
• Known or suspected carcinoma of the breast or reproductive organs.
• History of abnormal electrocardiogram (ECG) that, in the opinion of the investigator, is clinically significant and will prevent the participant from completing the study, including a QTc (corrected QT interval) of greater than 450 milliseconds (ms).

Sponsors & Collaborators

• Repros Therapeutics Inc.: lead

Study Sites (10)

Unknown Facility

Tucson, Arizona, 85712, United States

Location

Unknown Facility

Little Rock, Arkansas, 72205, United States

Location

Unknown Facility

Jacksonville, Florida, 32258, United States

Location

Unknown Facility

Margate, Florida, 33063, United States

Location

Unknown Facility

Metairie, Louisiana, 70001, United States

Location

Unknown Facility

Summerville, South Carolina, 29485, United States

Location

Unknown Facility

Houston, Texas, 77030, United States

Location

Unknown Facility

Riverton, Utah, 84065, United States

Location

Unknown Facility

Salt Lake City, Utah, 84124, United States

Location

Unknown Facility

Richmond, Virginia, 23235, United States

Location

Related Publications (1)

• Rolla E. Endometriosis: advances and controversies in classification, pathogenesis, diagnosis, and treatment. F1000Res. 2019 Apr 23;8:F1000 Faculty Rev-529. doi: 10.12688/f1000research.14817.1. eCollection 2019.

  PMID: 31069056 DERIVED

Related Links

• Sponsor corporate web page

MeSH Terms

Conditions

Endometriosis

Interventions

telapristone acetate

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Results Point of Contact

• Title: Therapeutic Area, Head
• Organization: Allergan

clinicaltrials@allergan.com

714-246-4500

Study Officials

• Anna Chan

  Allergan

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2012
• First Posted: November 19, 2012
• Study Start: May 2, 2013
• Primary Completion: March 15, 2017
• Study Completion: March 15, 2017
• Last Updated: July 23, 2019
• Results First Posted: July 23, 2019

Record last verified: 2019-07

Locations

US (10)