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

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

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

Study Overview

• Status: Completed
• Conditions: Uterine Hemorrhage; Leiomyoma
• Intervention / Treatment: Drug: Placebo; Drug: Ulipristal acetate (UPA)

• Study Type: Interventional
• Enrollment (Actual): 432
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8S4L8
      • Watson Investigational Site 140
    • Ottawa, Ontario, Canada, K1H7W9
      • Watson Investigational Site 144
• United States
  • Arizona
    • Mesa, Arizona, United States, 85209
      • Watson Investigational Site 138
    • Phoenix, Arizona, United States, 85032
      • Watson Investigational Site 147
    • Scottsdale, Arizona, United States, 85251
      • Watson Investigational Site 106
    • Tucson, Arizona, United States, 85712
      • Watson Investigational Site 124
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Watson Investigational Site 155
  • California
    • Encino, California, United States, 91436
      • Watson Investigational Site 155
    • Hawaiian Gardens, California, United States, 90716
      • Watson Investigational Site 157
    • La Mesa, California, United States, 91942
      • Watson Investigational Site 134
    • San Diego, California, United States, 92111
      • Watson Investigational Site 127
    • San Diego, California, United States, 92114
      • Watson Investigational Site 151
  • Colorado
    • Denver, Colorado, United States, 80209
      • Watson Investigational Site 159
  • Florida
    • Clearwater, Florida, United States, 33759
      • Watson Investigational Site 131
    • Miramar, Florida, United States, 33027
      • Watson Investigational Site 135
    • North Miami, Florida, United States, 33161
      • Watson Investigational Site 132
    • Orlando, Florida, United States, 32806
      • Watson Investigational Site 161
    • Plantation, Florida, United States, 33324
      • Watson Investigational Site 123
    • Sarasota, Florida, United States, 34239
      • Watson Investigational Site 112
    • Wellington, Florida, United States, 33414
      • Watson Investigational Site 102
    • West Palm Beach, Florida, United States, 33409
      • Watson Investigational Site 101
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Watson Investigational Site 160
    • Sandy Springs, Georgia, United States, 30328
      • Watson Investigational Site 103
    • Savannah, Georgia, United States, 31406
      • Watson Investigational Site 117
  • Illinois
    • Champaign, Illinois, United States, 61820
      • Watson Investigational Site 113
    • Schaumburg, Illinois, United States, 60173
      • Watson Investigational Site 119
  • Indiana
    • Brownsburg, Indiana, United States, 46112
      • Watson Investigational Site 162
    • Granger, Indiana, United States, 46530
      • Watson Investigational Site 104
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Watson Investigational Site 150
    • Metairie, Louisiana, United States, 70001
      • Watson Investigational Site 130
    • New Orleans, Louisiana, United States, 70115
      • Watson Investigational Site 116
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Watson Investigational Site 108
    • Las Vegas, Nevada, United States, 89128
      • Watson Investigational Site 107
  • New Jersey
    • Lawrenceville, New Jersey, United States, 08648
      • Watson Investigational Site 111
    • Moorestown, New Jersey, United States, 08057
      • Watson Investigational Site 158
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Watson Investigational Site 115
  • New York
    • Bronx, New York, United States, 10461
      • Watson Investigational Site 155
  • North Carolina
    • Durham, North Carolina, United States, 27713
      • Watson Investigational Site 126
    • Greensboro, North Carolina, United States, 27408
      • Watson Investigational Site 128
    • New Bern, North Carolina, United States, 28562
      • Watson Investigational Site 145
    • Raleigh, North Carolina, United States, 27612
      • Watson Investigational Site 146
    • Winston-Salem, North Carolina, United States, 27103
      • Watson Investigational Site 118
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Watson Investigational Site 155
    • Cleveland, Ohio, United States, 44106
      • Watson Investigational Site 155
    • Cleveland, Ohio, United States, 44122
      • Watson Investigational Site 148
    • Englewood, Ohio, United States, 45322
      • Watson Investigational Site 139
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19114
      • Watson Investigational Site 133
    • Pittsburgh, Pennsylvania, United States, 15206
      • Watson investigational site 142
    • West Reading, Pennsylvania, United States, 19611
      • Watson Investigational Site 105
  • South Carolina
    • Bluffton, South Carolina, United States, 29910
      • Watson Investigational Site 136
    • Charleston, South Carolina, United States, 29425
      • Watson Investigational Site 110
    • Columbia, South Carolina, United States, 29201
      • Watson Investigational Site 153
    • Greenville, South Carolina, United States, 29615
      • Watson Investigational Site 154
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Watson Investigational Site 155
  • Texas
    • Dallas, Texas, United States, 75231
      • Watson Investigational Site 122
    • Frisco, Texas, United States, 75035
      • Watson Investigational Site 114
    • Houston, Texas, United States, 77030
      • Watson Investigational Site 109
    • Houston, Texas, United States, 77054
      • Watson Investigational Site 155
    • San Antonio, Texas, United States, 78229
      • Watson Investigational Site 120
    • Webster, Texas, United States, 77598
      • Watson Investigational Site 129
  • Virginia
    • Norfolk, Virginia, United States, 23507-1627
      • Watson Investigational Site 152
    • Virginia Beach, Virginia, United States, 23456
      • Watson Investigational Site 137
  • Washington
    • Seattle, Washington, United States, 98105
      • Watson Investigational Site 121

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: UPA 5 mg:Placebo; 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: Placebo; Matching placebo tablet.; Drug: Ulipristal acetate (UPA); Ulipristal acetate (UPA) tablet.
EXPERIMENTAL: UPA 10 mg:Placebo; 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: Placebo; Matching placebo tablet.; Drug: Ulipristal acetate (UPA); Ulipristal acetate (UPA) tablet.
EXPERIMENTAL: UPA 5 mg:UPA 5 mg; 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: Placebo; Matching placebo tablet.; Drug: Ulipristal acetate (UPA); Ulipristal acetate (UPA) tablet.
EXPERIMENTAL: UPA 10 mg:UPA 10 mg; 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: Placebo; Matching placebo tablet.; Drug: Ulipristal acetate (UPA); Ulipristal acetate (UPA) tablet.
EXPERIMENTAL: Placebo:UPA 5 mg; 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: Placebo; Matching placebo tablet.; Drug: Ulipristal acetate (UPA); Ulipristal acetate (UPA) tablet.
EXPERIMENTAL: Placebo:UPA 10 mg; 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: Placebo; Matching placebo tablet.; Drug: Ulipristal acetate (UPA); Ulipristal acetate (UPA) tablet.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Allergan

Publications and helpful links

General Publications

• Coyne KS, Harrington A, Currie BM, Chen J, Gillard P, Spies JB. Psychometric validation of the 1-month recall Uterine Fibroid Symptom and Health-Related Quality of Life questionnaire (UFS-QOL). J Patient Rep Outcomes. 2019 Aug 23;3(1):57. doi: 10.1186/s41687-019-0146-x.
• Lukes AS, Soper D, Harrington A, Sniukiene V, Mo Y, Gillard P, Shulman L. Health-Related Quality of Life With Ulipristal Acetate for Treatment of Uterine Leiomyomas: A Randomized Controlled Trial. Obstet Gynecol. 2019 May;133(5):869-878. doi: 10.1097/AOG.0000000000003211.
• Liu JH, Soper D, Lukes A, Gee P, Kimble T, Kroll R, Mallick M, Chan A, Gillard P, Harrington A, Sniukiene V, Shulman LP. Ulipristal Acetate for Treatment of Uterine Leiomyomas: A Randomized Controlled Trial. Obstet Gynecol. 2018 Nov;132(5):1241-1251. doi: 10.1097/AOG.0000000000002942.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 29, 2014
• Primary Completion (ACTUAL): November 24, 2016
• Study Completion (ACTUAL): November 24, 2016

Study Registration Dates

• First Submitted: May 10, 2014
• First Submitted That Met QC Criteria: May 21, 2014
• First Posted (ESTIMATE): May 26, 2014

Study Record Updates

• Last Update Posted (ACTUAL): June 4, 2019
• Last Update Submitted That Met QC Criteria: May 15, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Uterine Diseases; Connective Tissue Diseases; Neoplasms, Connective Tissue; Neoplasms, Muscle Tissue; Hemorrhage; Leiomyoma; Myofibroma; Uterine Hemorrhage; Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Ulipristal acetate
• Other Study ID Numbers: UL1208

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No