Placebo-controlled Proof of Concept Study of Epelsiban in Women With Adenomyosis

Study Overview
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Brief Summary
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The primary objective of the study is to assess the efficacy, safety, and tolerability of epelsiban compared with placebo in treatment of women with adenomyosis. This is a 12-week, randomized, double-blind, placebo-controlled, parallel group study with an interim futility analysis. Subjects will be randomized 1:1:1 to receive 75 milligrams (mg) of epelsiban three times daily (TID), 200 mg of epelsiban TID, or placebo TID. The study will be composed of three periods: screening, treatment, and follow-up and the total time a subject will be in the study will be approximately 6 months.

Official Title
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A Phase II, Randomized, Placebo-Controlled, Double-Blind, Parallel Group, Proof of Concept Study With an Interim Futility Analysis of Epelsiban in Patients With Adenomyosis

Conditions
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Adenomyosis

Intervention / Treatment
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* Drug: Epelsiban
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eighteen to 55 years of age, inclusive Pre-menopausal with a history of regular menstrual cycles every 21-35 days and without intermenstrual bleeding heavier than spotting and staining. Females with adenomyosis confirmed on magnetic resonance imaging (MRI), - Females with heavy menstrual bleeding . Willing and able to collect all menstrual cycle by-products for each cycle from screening to follow up. Not pregnant as confirmed by a negative serum human chorionic gonadotropin Exclusion Criteria: A female subject will not be eligible for inclusion in this study if any of the following criteria apply: Abnormal gynecological examination other than adenomyosis and/or breast examination requiring intervention within six months of study start Abnormal endometrial biopsy within six months of starting study treatment. History of an endometrial ablation within 12 months of starting study treatment. Uterine artery embolization within six months of starting study treatment. Prior major uterine procedures or any other significant uterine abnormalities on MRI (previous caesarean section, dilation and curettage, and diagnostic hysteroscopy are permitted). Confirmed rectovaginal endometriosis in women who have undergone a prior laparoscopy. Active pelvic infection or current use of an intrauterine device within three months of screening. Women with a history of transfusion for heavy menstrual bleeding within the past 2 years or history of postpartum hemorrhage. Any uterine dimension >20 centimeter (cm). Other major causes of heavy menstrual bleeding - Use within 3 months or anticipated use of medications that modify reproductive function Use or anticipated use of the following drugs: anticoagulants aminocaproic acid ,or any other medications that affect menstrual bleeding such as tranexamic acid. Use of daily opioid pain medications other than with menses. Hemoglobin <8 grams (g)/deciliter. History of bleeding disorder or known presence of acquired or inherited thrombophilia, (sickle cell trait individuals are not excluded).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Epelsiban 75 mg<br>Approximately 24 subjects will receive 75 mg of epelsiban three times a day (TID) via oral administration | Drug: Epelsiban<br>* Epelsiban will be supplied as modified capsule shaped, white coated, oral tablet with a unit dose strength of 25 or 150 mg; to be taken with food or immediately after a meal, without chewing<br>|
| Experimental: Epelsiban 200 mg<br>Approximately 24 subjects will receive 200 mg of epelsiban TID via oral administration | Drug: Epelsiban<br>* Epelsiban will be supplied as modified capsule shaped, white coated, oral tablet with a unit dose strength of 25 or 150 mg; to be taken with food or immediately after a meal, without chewing<br>|
| Placebo Comparator: Placebo<br>Approximately 24 subjects will receive a matching placebo TID via oral administration | Drug: Placebo<br>* A matching placebo will be supplied as modified capsule shaped, white coated, oral tablet; to be taken with food or immediately after a meal, without chewing.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean percent change from baseline in monthly menstrual blood loss (MBL) to menstrual Cycle 3 | MBL will be measured from blood collected from menstrual cycle by-products and recovered by alkaline hematin method during each menstrual cycle | Baseline and end of menses Cycle 3 (approximately 12 weeks) | 
| Number of subjects with adverse events (AE) | An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product; safety and tolerability as assessed by incidence of adverse events | Up to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in monthly menstrual blood loss (MBL) at menstrual Cycle 1, 2, and 3 | MBL will be measured from blood collected from menstrual cycle by-products | Baseline, and end of menses Cycle 1, 2, and 3 (approximately 12 weeks) | 
| Average daily dysmenorrhea score from Day -1 to Day 2 in each cycle | Average daily dysmenorrhea score from Day -1 to Day 2 of menses | Up to 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heavy menstrual bleeding, Adenomyosis, Safety, Epelsiban, Tolerability, Proof of concept