An Extension Study of 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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To determine the safety of extended treatment with Proellex® in women who have successfully completed either study ZPV-201 [NCT02323646] or ZPU-203 [NCT02301897] and meet eligibility criteria.

Detailed Description
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This study will be for participants who had completed either ZPV-201 or ZPU-203.

Official Title
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An Open-Label Extension Study of 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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completed either study ZPV-201 [NCT02323646] or ZPU-203 [NCT02301897] Agreement not to attempt to become pregnant during the trial Agreement to use alcohol in moderation and record the daily consumption (note: elevated liver enzymes may result in discontinuation from the study) Ability to complete a daily subject 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 off-drug intervals. 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 Visit 1 Subject is available for all treatment and follow-up visits Exclusion Criteria: Subject had a significant decrease in bone mineral density while participating in ZPV-201 or ZPU-203 (total hip or spine measurement decreased by 5% or more) Subject has undergone hysterectomy and/or bilateral oophorectomy since enrollment in ZPV-201 or ZPU-203 Subject is pregnant or lactating or is attempting or expecting to become pregnant during the entire study period Subjects with abnormally high liver enzymes or liver disease. [alanine aminotransferase (ALT) or aspartate aminotransferase (AST) exceeding 2 x upper limit of normal (ULN) and total bilirubin exceeding 1.5 x ULN at Visit 1 and confirmed on repeat]. Subject has a hemoglobin of <7.5 grams per deciliter (g/dL) at Visit 1 Concurrent use of any testosterone, progestin, androgen, estrogen, anabolic steroids, dehydroepiandrosterone (DHEA) or hormonal products for at least 2 weeks prior to Visit 1 Use of oral contraceptives in the 30 days preceding screening. Use of Depo-Provera® in the preceding 10 months Use of Gonadotrophin releasing hormone agonist (GnRHas) (e.g. Lupron Depot) within 3 months prior to screening (Lupron Depot must have a wash-out period of 3 months prior to screening) Has an intra-uterine device (IUD) in place Current cervical dysplasia classified as Atypical Squamous Cells of Undetermined Significance (ASCUS) associated with high-risk human papilloma virus (HPV) Current diagnosis of Low/High Grade Squamous Intraepithelial Lesion (LGSIL or HGSIL), endometrial polyps or hyperplasia Observation or history of abnormal endometrial biopsy including the presence of endometrial intraepithelial neoplasia (EIN) Recent history (within past 6 months) of alcoholism or drug abuse Endometrial stripe ≥18 mm in thickness at Visit 1 (subject may be enrolled with sponsor approval) Subject is currently taking cimetidine or spironolactone or has taken them in the last 30 days Clinically significant abnormal findings on Visit 1 examination and laboratory assessments or any condition which in the opinion of the investigator would interfere with the subject's ability to comply with the study instructions or endanger the subject 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telapristone Acetate 12 mg<br>Telapristone acetate 12 milligrams (mg), orally, once daily for two 18-weeks courses (Treatment Courses 1 and 2) separated by an off-drug interval (ODI). | Drug: Telapristone acetate<br>* Telapristone acetate, orally, once daily for three 18-weeks courses separated by an 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 | 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 | 
| Percentage Change From Baseline in Total Uterine Fibroid System Quality of Life Survey System Severity (UFS-SSS) Score | 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 to the end of 18-weeks Treatment Course 1 | 
| Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 1 | 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 to the end of 18-weeks Treatment Course 1 | 
| Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 2 | 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 to the end of 18-weeks Treatment Course 1 | 
| Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 3 | 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 to the end of 18-weeks Treatment Course 1 | 
| Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 4 | 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 to the end of 18-weeks Treatment Course 1 | 
| Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 5 | 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 to the end of 18-weeks Treatment Course 1 | 
| Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 6 | 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 to the end of 18-weeks Treatment Course 1 | 
| Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 7 | 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 night time 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 to the end of 18-weeks Treatment Course 1 | 
| Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 8 | 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 to the end of 18-weeks Treatment Course 1 | 
| Change From Baseline in Pictorial Blood Loss Assessment Chart (PBAC) Score | 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 to the end of 18-weeks Treatment Course 1 | 
| Percentage Change From Baseline in Total Uterine Fibroid Volume | The total uterine fibroid volume was measured by Magnetic Resonance Imaging (MRI). A negative percentage change from Baseline indicates improvement. | Baseline to the end of 18-weeks Treatment Course 1 |