Safety and Efficacy of Telapristone Acetate (Proellex®) Administered Vaginally for the Treatment of Uterine Fibroids

Study Overview
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Brief Summary
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The primary objective of this study is to determine the safety and efficacy of two vaginal doses of Proellex® administered for up to 2 courses of treatment (18 weeks each), each separated by an Off-Drug Interval (ODI), to premenopausal women with symptomatic uterine fibroids.

Official Title
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A Phase 2, Multi-Center, Parallel Design, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of 6 and 12 mg Proellex® (Telapristone Acetate) Administered Vaginally in the Treatment of Premenopausal Women With Confirmed Symptomatic Uterine Fibroids

Conditions
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Uterine Fibroids

Intervention / Treatment
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* Drug: Placebo
* Drug: Telapristone Acetate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult females between 18 and 47 years. Have a history of at least 3 regular menstrual cycles in which menorrhagia is due to uterine fibroids. Must have uterine fibroids. Agreement not to attempt to become pregnant during the trial. Agreement to use only sanitary pads provided throughout the course of the study, tampon use is prohibited . Ability to complete a daily Participant diary and study procedures in compliance with the protocol. Have a negative pregnancy test at the Screening and Baseline visits, and subsequent study visits. A Body Mass Index (BMI) between 18 and 45 inclusive. Menstrual blood loss > 80 milliliters (mL) by alkaline hematin assay. Exclusion Criteria: 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 entire study period. Received an investigational drug in the 30 days prior to the screening for this study. History of Polycystic Ovarian Syndrome (PCOS). Concurrent use of any testosterone, progestin, androgen, estrogen, anabolic steroids, Dihydroepiandrosterone (DHEA) or hormonal products for at least 2 weeks prior to screening and during the study. Use of oral contraceptives in the preceding 30 days. Use of Depo-Provera® in the preceding 10 months. Use of Gonadotropin Releasing Hormone (GnRHas) (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). Has an Intra Uterine device (IUD) in place. Known or suspected carcinoma of the breast or reproductive organs. Recent history (within past 6 months) of alcoholism or drug abuse. Clinically significant abnormal findings on screening examination and laboratory assessments 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 47 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Following the baseline assessment no treatment period, matching placebo, vaginally, once daily for 18 weeks (Course 1) and repeated for an additional 18 weeks (Course 2) following the ODI. | Drug: Placebo<br>* Matching placebo, vaginally, once daily for 18 weeks (Course 1) and repeated for an additional 18 weeks (Course 2) following the ODI.<br>|
| Experimental: Telapristone Acetate 6 mg<br>Following the baseline assessment no treatment period, telapristone acetate 6 milligrams (mg), vaginally, once daily for 18 weeks (Course 1) and repeated for an additional 18 weeks (Course 2) following the ODI. | Drug: Telapristone Acetate<br>* Telapristone acetate, vaginally, once daily for 18 weeks (Course 1) and repeated for an additional 18 weeks (Course 2) following the ODI.<br>* Other names: Proellex®;|
| Experimental: Telapristone Acetate 12 mg<br>Following the baseline assessment no treatment period, telapristone acetate 12mg, vaginally, once daily for 18 weeks (Course 1) and repeated for an additional 18 weeks (Course 2) following the ODI. | Drug: Telapristone Acetate<br>* Telapristone acetate, vaginally, once daily for 18 weeks (Course 1) and repeated for an additional 18 weeks (Course 2) following the ODI.<br>* Other names: Proellex®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants in Amenorrhea at the End of Treatment Course 1 | Amenorrhea was defined as any 28-day period during treatment (not including the ODI) without a bleeding intensity score >1. Participants were provided with a daily diary and Pictorial Blood Loss Assessment Chart (PBAC) to record information about the menstrual blood loss (MBL). Bleeding intensity was graded on a 5-point scale where: 1=spotting to 5=heavy bleeding. | At the end of 18-weeks Treatment Course 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants in Amenorrhea at the End of Treatment Course 2 | Amenorrhea was defined as any 28-day period during treatment (not including the ODI) without a bleeding intensity score >1 after 2 courses of treatment. Participants were provided with a daily diary and (PBAC) to record information about the MBL. Bleeding intensity was graded on a 5-point scale where: 1=spotting to 5=heavy bleeding. | At the end of 18-weeks Treatment Course 2 | 
| Percentage Change in PBAC Scores From Baseline to the End of Treatment Courses 1 and 2 | Uterine bleeding was assessed with the use of the PBAC, a validated self-reporting method to estimate menstrual blood loss. Participants recorded daily the number of tampons and towels used and the degree to which individual items were soiled with blood (plus small or large clots). Pictorial scores range from score 1 for slightly stained tampon/towel, 5 for a partially stained tampon/towel, 10 for a completely saturated tampon, 20 for a completely saturated towel, and 5 for each episode of flooding and for each blood clot larger than a quarter in size. Total score can range from 0 (no bleeding) to >500. Higher scores indicate more bleeding. Lower scores indicate less bleeding. A negative change from Baseline indicates improvement (reduction in bleeding). | Baseline (No treatment period) to the end of 18-weeks Treatment Course 1 and the end of 18-weeks Treatment Course 2 | 
| Percentage Change in Transformed Total Uterine Fibroid System Quality of Life Survey System Severity (UFS-SSS) Score From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit | UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. Each question was answered on a 5-point scale where 1=Not at all to 5=A very great deal. The sum of the total scores was transformed to a range of 0=no symptoms (best) to 100=most severe symptoms (worst). A negative percentage change from Baseline indicates improvement. | Baseline (No treatment period) to the end of 18-weeks Treatment Course 1, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 Follow-up Visit | 
| Percentage Change in the Individual UFS-SSS Subscale Score Question 1 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit | UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 1: During the previous 3 months how distressed were you by heavy bleeding during your menstrual period? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement. | Baseline (No treatment period) to the end of 18-weeks Treatment Course 1, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 Follow-up Visit | 
| Percentage Change in the Individual UFS-SSS Subscale Score Question 2 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit | UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 2: During the previous 3 months how distressed were you by passing blood clots during your menstrual period? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement. | Baseline (No treatment period) to the end of 18-weeks Treatment Course 1, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 Follow-up Visit | 
| Percentage Change in the Individual UFS-SSS Subscale Score Question 3 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit | UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 3: During the previous 3 months how distressed were you by fluctuation in the duration of your menstrual period compared to your previous cycle? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement. | Baseline (No treatment period) to the end of 18-weeks Treatment Course 1, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 Follow-up Visit | 
| Percentage Change in the Individual UFS-SSS Subscale Score Question 4 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit | UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 4: During the previous 3 months how distressed were you by fluctuation in the length of your monthly cycle compared to your previous cycles? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement. | Baseline (No treatment period) to the end of 18-weeks Treatment Course 1, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 Follow-up Visit | 
| Percentage Change in the Individual UFS-SSS Subscale Score Question 5 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit | UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 5: During the previous 3 months how distressed were you by feeling tightness or pressure in your pelvic area? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement. | Baseline (No treatment period) to the end of 18-weeks Treatment Course 1, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 Follow-up Visit | 
| Percentage Change in the Individual UFS-SSS Subscale Score Question 6 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit | UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 6: During the previous 3 months how distressed were you by frequent urination during the daytime hours? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement. | Baseline (No treatment period) to the end of 18-weeks Treatment Course 1, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 Follow-up Visit | 
| Percentage Change in the Individual UFS-SSS Subscale Score Question 7 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit | UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 7: During the previous 3 months how distressed were you by frequent nighttime urination? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement. | Baseline (No treatment period) to the end of 18-weeks Treatment Course 1, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 Follow-up Visit | 
| Percentage Change in the Individual UFS-SSS Subscale Score Question 8 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit | UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 8: During the previous 3 months how distressed were you by feeling fatigued? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement. | Baseline (No treatment period) to the end of 18-weeks Treatment Course 1, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 Follow-up Visit | 
| Percentage Change in Total Uterine Fibroid Volume From Baseline to the End of Treatment Courses 1 and 2 | The total uterine fibroid volume was measured by Magnetic Resonance Imaging (MRI). A negative change from Baseline indicates improvement. | Baseline (No treatment period) to the end of 18-weeks Treatment Course 1 and the end of 18-weeks Treatment Course 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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uterine fibroids, leiomyoma, fibroid tumor, fibroma