A Multi-Center, Parallel Design, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of 6 and 12 mg Proellex® (Telapristone Acetate) Administered Orally in the Treatment of Premenopausal Women With Confirmed Symptomatic 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 oral 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 Orally 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: Telapristone Acetate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is a pre-menopausal female, between 18 and 47 years Participant has a history of at least 3 regular menstrual cycles in which menorrhagia (heavy bleeding) is due to uterine fibroids Confirmed uterine fibroid(s) at screening Visit 1 historical pictorial blood loss assessment chart of >120 milliliters (mL) of blood loss, to ensure participants have a menstrual blood loss of at least 80 mL by Alkaline Hematin Assay (during the baseline assessment period). A Body Mass Index (BMI) between 18 and 45 inclusive Exclusion Criteria: Participant is 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 Has an intrauterine device in place Observation or history of abnormal endometrial biopsy including the presence of endometrial intraepithelial neoplasia Participants with abnormally high liver enzymes or liver disease

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, orally, once daily for 18 weeks (Treatment Course 1) and repeated for an additional 18 weeks (Treatment Course 2) following the off drug interval (ODI). | Drug: Placebo<br>* Matching placebo, orally, once daily for 18 weeks (Course 1) and repeated for an additional 18 weeks (Course 2) following the ODI.<br>* Other names: sugar pill;|
| Experimental: Telapristone Acetate 6 mg<br>Following the baseline assessment no treatment period, telapristone acetate 6 milligrams (mg), orally, once daily for 18 weeks (Treatment Course 1) and repeated for an additional 18 weeks (Treatment Course 2) following the ODI. | Drug: Telapristone Acetate<br>* Telapristone acetate, orally, 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 12 mg, orally, once daily for 18 weeks (Treatment Course 1) and repeated for an additional 18 weeks (Treatment Course 2) following the ODI. | Drug: Telapristone Acetate<br>* Telapristone acetate, orally, 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 no bleeding intensity score greater than 1 using the Daily Diary Card during the 28 days leading up to the last day of dosing at Week 18. Bleeding intensity was graded on a 5-point scale where: 0=no bleeding to 4=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 no bleeding intensity score greater than 1 using the Daily Diary Card during the 28 days leading up to the last day of dosing at Week 18. Bleeding intensity was graded on a 5-point scale where: 0=no bleeding to 4=heavy bleeding. | At the end of 18-weeks Treatment Course 2 | 
| Change in Pictorial Blood Loss Assessment Chart (PBAC) Score From Baseline to the End of Treatment Courses 1 and 2, ODI Course 1 and the Course 2 Week 28 Follow-up (FU) Visit | 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, the end of ODI Course 1, the end of 18-weeks Treatment Course 2 and the Course 2 Week 28 FU Visit | 
| Percentage Change in PBAC Score From Baseline to the End of Treatment Courses 1 and 2, ODI Course 1 and the Course 2 Week 28 FU Visit | 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 percentage change from Baseline indicates improvement (reduction in bleeding). | Baseline (No treatment period) to the end of 18-weeks Treatment Course 1, the end of ODI Course 1, the end of 18-weeks Treatment Course 2 and the Course 2 Week 28 FU Visit | 
| Percentage Change in Uterine Fibroid System Quality of Life Survey System Severity (UFS-SSS) Score From Baseline to the End of Treatment Courses 1 and 2, On-drug Course 2 and the Course 2 Week 24 FU 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 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, On-drug Course 2, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 FU Visit | 
| Percentage Change in the Individual UFS-SSS Subscale Score Question 1 From Baseline to the End of Treatment Courses 1 and 2, On-drug Course 2 and the Course 2 Week 24 FU 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, On-drug Course 2, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 FU Visit | 
| Percentage Change in the Individual UFS-SSS Subscale Score Question 2 From Baseline to the End of Treatment Courses 1 and 2, On-drug Course 2 and the Course 2 Week 24 FU 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, On-drug Course 2, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 FU Visit | 
| Percentage Change in the Individual UFS-SSS Subscale Score Question 3 From Baseline to the End of Treatment Courses 1 and 2, On-drug Course 2 and the Course 2 Week 24 FU 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, On-drug Course 2, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 FU Visit | 
| Percentage Change in the Individual UFS-SSS Subscale Score Question 4 From Baseline to the End of Treatment Courses 1 and 2, On-drug Course 2 and the Course 2 Week 24 FU 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, On-drug Course 2, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 FU Visit | 
| Percentage Change in the Individual UFS-SSS Subscale Score Question 5 From Baseline to the End of Treatment Courses 1 and 2, On-drug Course 2 and the Course 2 Week 24 FU 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, On-drug Course 2, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 FU Visit | 
| Percentage Change in the Individual UFS-SSS Subscale Score Question 6 From Baseline to the End of Treatment Courses 1 and 2, On-drug Course 2 and the Course 2 Week 24 FU 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, On-drug Course 2, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 FU Visit | 
| Percentage Change in the Individual UFS-SSS Subscale Score Question 7 From Baseline to the End of Treatment Courses 1 and 2, On-drug Course 2 and the Course 2 Week 24 FU 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, On-drug Course 2, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 FU Visit | 
| Percentage Change in the Individual UFS-SSS Subscale Score Question 8 From Baseline to the End of Treatment Courses 1 and 2, On-drug Course 2 and the Course 2 Week 24 FU 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, On-drug Course 2, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 FU Visit | 
| Percentage Change in Total Uterine Fibroid Volume From Baseline to the End of Treatment Courses 1 and 2, On-drug Course 2 and the Course 2 Off-drug | The total uterine fibroid volume was measured by Magnetic Resonance Imaging (MRI). A negative percentage change from Baseline indicates improvement. | Baseline (No treatment period) to the end of 18-weeks Treatment Course 1, On-drug Course 2, the end of 18-weeks Treatment Course 2 and the Course 2 Off-drug |