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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Adenomyosis
• Intervention / Treatment: Drug: Epelsiban; Drug: Placebo

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, DC, District of Columbia, United States, 20036
      • GSK Investigational Site
  • Florida
    • West Palm Beach, Florida, United States, 33409
      • GSK Investigational Site
  • Illinois
    • Champaign, Illinois, United States, 61820
      • GSK Investigational Site
  • Louisiana
    • Mandeville, Louisiana, United States, 70471
      • GSK Investigational Site
    • Metairie, Louisiana, United States, 70006
      • GSK Investigational Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • GSK Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • GSK Investigational Site
  • New Jersey
    • Lawrenceville, New Jersey, United States, 08648
      • GSK Investigational Site
  • North Carolina
    • Durham, North Carolina, United States, 27713
      • GSK Investigational Site
    • Raleigh, North Carolina, United States, 27612
      • GSK Investigational Site
  • Ohio
    • Englewood, Ohio, United States, 45322
      • GSK Investigational Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15206
      • GSK Investigational Site
  • Texas
    • Houston, Texas, United States, 77030
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Epelsiban 75 mg; Approximately 24 subjects will receive 75 mg of epelsiban three times a day (TID) via oral administration	Drug: Epelsiban; 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
Experimental: Epelsiban 200 mg; Approximately 24 subjects will receive 200 mg of epelsiban TID via oral administration	Drug: Epelsiban; 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
Placebo Comparator: Placebo; Approximately 24 subjects will receive a matching placebo TID via oral administration	Drug: Placebo; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (Actual): October 1, 2016
• Study Completion (Anticipated): October 1, 2016

Study Registration Dates

• First Submitted: June 6, 2016
• First Submitted That Met QC Criteria: June 6, 2016
• First Posted (Estimate): June 9, 2016

Study Record Updates

• Last Update Posted (Estimate): January 18, 2017
• Last Update Submitted That Met QC Criteria: January 16, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Safety; Tolerability; Adenomyosis; Proof of concept; Heavy menstrual bleeding; Epelsiban
• Additional Relevant MeSH Terms: Uterine Diseases; Adenomyosis
• Other Study ID Numbers: 201580