A Study of the Efficacy and Safety of Ulipristal Acetate Intermittent Treatment for Abnormal Uterine Bleeding Associated With Leiomyomas

Study Overview
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Brief Summary
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This study will evaluate the superiority of ulipristal acetate versus placebo for the treatment of abnormal uterine bleeding associated with uterine fibroids

Official Title
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A Randomized, Placebo-Controlled, Parallel Group, Multicenter Study to Evaluate the Efficacy and Safety of Ulipristal Acetate for the Intermittent Treatment of Abnormal Uterine Bleeding Associated With Leiomyomas

Conditions
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Leiomyoma, Uterine Hemorrhage

Intervention / Treatment
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* Drug: Ulipristal acetate (UPA)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Premenopausal women, 18-50 years, inclusive. Cyclic abnormal uterine bleeding (heavy or prolonged). Menstrual blood loss (MBL) of ≥ 80 mL as measured by the alkaline hematin method in the first 8 days of menses. Minimum of one discrete leiomyoma observable by transvaginal ultrasound. Endometrial biopsy without evidence of malignancy or atypical or non-atypical hyperplasia. Exclusion Criteria: History of uterine surgery that would interfere with the study endpoints. Known coagulation disorder including bleeding disorder or clotting disorder. History of, or current uterine, cervix, ovarian, or breast cancer. Alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), or total bilirubin two times or greater than the upper limit of normal range.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: UPA 5 mg:Placebo<br>Ulipristal Acetate (UPA) 5 mg tablet plus matching placebo 10 mg tablet, orally, once daily for 12 weeks in Treatment Course 1; followed by a 2 menses drug-free interval; followed by matching placebo tablets (5 mg and 10 mg), orally, once daily for 12 weeks in Treatment Course 2. | Drug: Ulipristal acetate (UPA)<br>* Ulipristal acetate (UPA) tablet.<br>Drug: Placebo<br>* Matching placebo tablet.<br>|
| Experimental: UPA 10 mg:Placebo<br>UPA 10 mg tablet plus matching placebo 5 mg tablet, orally, once daily for 12 weeks in Treatment Course 1; followed by a 2 menses drug-free interval; followed by matching placebo tablets (5 mg and 10 mg), orally, once daily for 12 weeks in Treatment Course 2. | Drug: Ulipristal acetate (UPA)<br>* Ulipristal acetate (UPA) tablet.<br>Drug: Placebo<br>* Matching placebo tablet.<br>|
| Experimental: UPA 5 mg:UPA 5 mg<br>UPA 5 mg tablet plus matching placebo 10 mg tablet, orally, once daily in both Treatment Course 1 and Treatment Course 2. There was a 2 menses drug-free interval in between courses. | Drug: Ulipristal acetate (UPA)<br>* Ulipristal acetate (UPA) tablet.<br>Drug: Placebo<br>* Matching placebo tablet.<br>|
| Experimental: UPA 10 mg:UPA 10 mg<br>UPA 10 mg tablet plus matching placebo 5 mg tablet, orally, once daily in both Treatment Course 1 and Treatment Course 2. There was a 2 menses drug-free interval in between courses. | Drug: Ulipristal acetate (UPA)<br>* Ulipristal acetate (UPA) tablet.<br>Drug: Placebo<br>* Matching placebo tablet.<br>|
| Experimental: Placebo:UPA 5 mg<br>Matching placebo tablets (5 mg and 10 mg) orally, once daily for 12 weeks in Treatment Course 1; followed by a 2 menses drug-free interval; followed by UPA 5 mg tablet plus matching placebo 10 mg tablet, orally, once daily for 12 weeks in Treatment Course 2. | Drug: Ulipristal acetate (UPA)<br>* Ulipristal acetate (UPA) tablet.<br>Drug: Placebo<br>* Matching placebo tablet.<br>|
| Experimental: Placebo:UPA 10 mg<br>Matching placebo tablets (5 mg and 10 mg), orally, once daily for 12 weeks in Treatment Course 1; followed by a 2 menses drug-free interval; followed by UPA 10 mg tablet plus matching placebo 5 mg tablet, orally, once daily for 12 weeks in Treatment Course 2. | Drug: Ulipristal acetate (UPA)<br>* Ulipristal acetate (UPA) tablet.<br>Drug: Placebo<br>* Matching placebo tablet.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Absence of Bleeding During the Last 35 Consecutive Days on Treatment in Treatment Course 1 | Participants recorded bleeding in a daily diary. Absence of bleeding was defined as no bleeding days (i.e., no entries for bleeding or heavy bleeding; however, spotting was allowed), during the last 35 consecutive days on treatment in Treatment Course 1. | Last 35 consecutive days on treatment in the 12-Week Treatment Course 1 | 
| Time to Absence of Bleeding on Treatment During Treatment Course 1 | Time to absence of bleeding was defined as the duration in days from first dose to the first day in the time interval in which absence of bleeding occurs and persists through the last dose in the first treatment course. The persistence of absence of bleeding occurred for a minimum of 35 consecutive days counting backward from the last dose in Treatment Course 1. | From first dose up to the end of the 12-Week Treatment Course 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Absence of Bleeding From Day 11 Through the End of Treatment Course 1 | Participants recorded bleeding in a daily diary. Absence of bleeding was defined as no bleeding days (i.e., no entries for bleeding or heavy bleeding; however, spotting was allowed), from Day 11 to the end of treatment in Treatment Course 1. | Day 11 through the end of treatment in the 12-Week Treatment Course 1 | 
| Percentage of Participants With Absence of Bleeding During the Last 35 Consecutive Days on Treatment in Treatment Course 2 | Participants recorded bleeding in a daily diary. Absence of bleeding was defined as no bleeding days (i.e., no entries for bleeding or heavy bleeding; however, spotting was allowed), during the last 35 consecutive days on treatment in Treatment Course 2. | Last 35 consecutive days on treatment in the 12-Week Treatment Course 2 | 
| Time to Absence of Bleeding on Treatment During Treatment Course 2 | Time to absence of bleeding is defined as the duration in days from first dose in treatment course 2 to the first day in the time interval in which absence of bleeding occurs and persists through the last dose in the second treatment course. The persistence of absence of bleeding occurred for a minimum of 35 consecutive days counting backward from the last dose in Treatment Course 2. | From first dose up to the end of treatment in the 12-Week Treatment Course 2 | 
| Change From Baseline in Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL) Revised Activities Subscale Score at the End of Treatment Course 1 | The UFS-QOL is a uterine fibroid-specific questionnaire consisting of 37 questions developed to evaluate symptoms of uterine fibroids and their impact on health-related quality of life in women with leiomyomas. The first 8 questions comprise the Symptom Severity subscale to assess symptoms experienced by women with uterine leiomyomas, the remaining 29 questions comprise 6 subscales (Concern, Activities, Energy/mood, Control, Self-consciousness, Sexual Function) which overall deal with women's feelings and experiences regarding impact of uterine leiomyoma symptoms on her life. Each item is scored between 1 and 5, where 1=none of the time or not at all and 5=all of the time or a very great deal. A Revised Activities subscale was created to include the most relevant items pertaining to physical and social activities with a total possible score of 0 to 100. Higher Revised Activities subscale scores indicate less impact on activities. A positive change from Baseline indicates improvement. | Baseline (Day 1-4) to End of 12-Week Treatment Course 1 |