LIBERTY 1: Efficacy & Safety Study of Relugolix in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids

NCT03049735 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: MVT-601-30012016-003727-27
• Study Type: interventional
• Target: 388
• Locations: 6 countries
• Sites: 110

Brief Summary

The purpose of this study is to determine the benefit of relugolix 40 milligrams (mg) once a day co-administered with estradiol (E2) 1 mg and norethindrone acetate (NETA) 0.5 mg compared with placebo for 24 weeks on heavy menstrual bleeding associated with uterine fibroids.

Conditions

Heavy Menstrual Bleeding; Uterine Fibroid

Keywords

Uterine Fibroid; Heavy Menstrual Bleeding; Menstrual Blood Volume

Outcome Measures

Primary Outcomes (1)

• Percentage Of Participants Who Achieved A Menstrual Blood Loss (MBL) Volume Of < 80 mL And A ≥ 50% Reduction From Baseline MBL Volume With Relugolix Plus E2/NETA

  A responder was a participant who had MBL volume of \< 80 mL and at least a 50% reduction from baseline MBL volume over the last 35 days of treatment (up to Week 24). All returned feminine products collected at each clinical visit were analyzed by the alkaline hematin method to obtain the MBL volume. MBL volume was measured over the Week 24/early termination feminine product collection interval (up to 35 days prior to the last dose of treatment). The percentage of participants who were responders are presented. As per the objective of the study, the pre-specified primary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

  From Baseline up to last 35 days of treatment (up to Week 24)

Secondary Outcomes (43)

• Percentage Of Participants With Amenorrhea Over The Last 35 Days Of Treatment

  From Baseline up to last 35 days of treatment (up to Week 24)

• Percent Change From Baseline At Week 24 In MBL Volume

  Baseline, Week 24

• Percentage Of Participants With A Hemoglobin Level ≤ 10.5 g/dL At Baseline Who Achieved An Increase Of > 2 g/dL From Baseline At Week 24

  From Baseline up to Week 24

• Percentage Of Participants With A Maximum NRS Score ≤ 1 For Uterine Fibroid-Associated Pain Over The Last 35 Days Of Treatment

  From Baseline up to Week 24

• Percent Change From Baseline At Week 24 In Primary Uterine Fibroid Volume

  Baseline, Week 24

Study Arms (3)

Relugolix plus E2/NETA (Group A)

EXPERIMENTAL

Relugolix co-administered with E2/NETA for 24 weeks.

Drug: Relugolix; Drug: Estradiol/norethindrone acetate

Relugolix plus Delayed E2/NETA (Group B)

EXPERIMENTAL

Relugolix co-administered with E2/NETA placebo for 12 weeks, followed by relugolix co-administered with E2/NETA for 12 weeks.

Drug: Relugolix; Drug: Estradiol/norethindrone acetate; Drug: Estradiol/norethindrone acetate placebo

Placebo (Group C)

PLACEBO COMPARATOR

Relugolix placebo co-administered with E2/NETA placebo for 24 weeks.

Drug: Estradiol/norethindrone acetate placebo; Drug: Relugolix placebo

Interventions

Relugolix DRUG

Relugolix (40 mg) tablet administered orally once daily.

Also known as: TAK-385, MVT-601

Relugolix plus Delayed E2/NETA (Group B); Relugolix plus E2/NETA (Group A)

Estradiol/norethindrone acetate DRUG

E2 (1.0 mg)/NETA (0.5 mg) co-formulated capsule administered orally once daily.

Also known as: E2/NETA, low-dose hormonal add-back

Relugolix plus Delayed E2/NETA (Group B); Relugolix plus E2/NETA (Group A)

Estradiol/norethindrone acetate placebo DRUG

E2 (0 mg)/NETA (0 mg) placebo capsule administered orally once daily and designed to match the capsule containing E2/NETA in size, shape, color, and odor.

Placebo (Group C); Relugolix plus Delayed E2/NETA (Group B)

Relugolix placebo DRUG

Relugolix (0 mg) placebo tablet administered orally once daily and manufactured to match the relugolix tablet in size, shape, color, and odor.

Placebo (Group C)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Premenopausal female aged 18 to 50 years old (inclusive) on the day of signing and dating the informed consent form.
• Has regularly occurring menstrual periods of ≤ 14 days duration with a cycle of 21 to 38 days from the start of 1 menstrual period until the start of the next, by participant history for at least 3 months prior to the first screening visit.
• Has a diagnosis of uterine fibroids that is confirmed by a transvaginal and/or transabdominal ultrasound performed during the screening period.
• Has heavy menstrual bleeding associated with uterine fibroids as evidenced by an MBL of ≥ 160 milliliter (mL) during 1 cycle or ≥ 80 mL per cycle for 2 menstrual cycles as measured by the alkaline hematin method during the screening period.

You may not qualify if:

• Has transvaginal and/or transabdominal ultrasound during the screening period demonstrating pathology other than uterine fibroids that could be responsible for or contributing to the patient's heavy menstrual bleeding.
• Has known rapidly enlarging uterine fibroids in the opinion of the investigator.
• Has a weight that exceeds the weight limit of the DXA scanner or has a condition that precludes an adequate DXA measurement at the lumbar spine and proximal femur.
• Has a history of or currently has osteoporosis, or other metabolic bone disease, hyperparathyroidism, hyperprolactinemia, hyperthyroidism, anorexia nervosa, or low traumatic (from the standing position) or atraumatic fracture (toe, finger, skull, face and ankle fractures are allowed). A history of successfully treated hyperparathyroidism, hyperprolactinemia, or hyperthyroidism is allowed if the participant's bone mineral density is within normal limits.
• Has a history of the use of bisphosphonates, calcitonin, calcitriol, ipriflavone, teriparatide, denosumab, or any medication other than calcium and vitamin D preparations to treat bone mineral density loss.
• Has been a participant in an investigational drug or device study within the 1 month prior to the first screening visit.

Sponsors & Collaborators

• Myovant Sciences GmbH: lead

Study Sites (110)

Andalusia

Andalusia, Alabama, 36420, United States

Location

Mobile

Mobile, Alabama, 36608, United States

Location

Little Rock

Little Rock, Arkansas, 72205, United States

Location

La Mesa

La Mesa, California, 91942, United States

Location

Lomita

Lomita, California, 90717, United States

Location

Norwalk

Norwalk, California, 90650, United States

Location

Oceanside

Oceanside, California, 92056, United States

Location

San Diego

San Diego, California, 92108, United States

Location

San Diego

San Diego, California, 92111, United States

Location

Denver

Denver, Colorado, 80209, United States

Location

Aventura

Aventura, Florida, 33180, United States

Location

Brandon

Brandon, Florida, 33510, United States

Location

Clearwater

Clearwater, Florida, 33759, United States

Location

Clermont

Clermont, Florida, 34711, United States

Location

Fort Myers

Fort Myers, Florida, 33912, United States

Location

Hialeah

Hialeah, Florida, 33012, United States

Location

Hialeah

Hialeah, Florida, 33016, United States

Location

Jacksonville

Jacksonville, Florida, 32207, United States

Location

Lauderdale Lakes

Lauderdale Lakes, Florida, 33319, United States

Location

Margate

Margate, Florida, 33063, United States

Location

Miami

Miami, Florida, 33155, United States

Location

Miami

Miami, Florida, 33165, United States

Location

Miami

Miami, Florida, 33176, United States

Location

Orlando

Orlando, Florida, 32806, United States

Location

Orlando

Orlando, Florida, 32808, United States

Location

Palm Harbor

Palm Harbor, Florida, 34684, United States

Location

South Miami

South Miami, Florida, 33143, United States

Location

Tampa

Tampa, Florida, 33613, United States

Location

West Palm Beach

West Palm Beach, Florida, 33409, United States

Location

Weston

Weston, Florida, 33327, United States

Location

Atlanta

Atlanta, Georgia, 30342, United States

Location

Atlanta

Atlanta, Georgia, 49074, United States

Location

Augusta

Augusta, Georgia, 30912, United States

Location

College Park

College Park, Georgia, 30349, United States

Location

Richland

Richland, Georgia, 99352, United States

Location

Oakbrook

Oakbrook Terrace, Illinois, 60523, United States

Location

Lafayette

Lafayette, Indiana, 47905, United States

Location

Covington

Covington, Louisiana, 70433, United States

Location

Shreveport

Shreveport, Louisiana, 71118, United States

Location

St. Louis

St Louis, Missouri, 63141, United States

Location

Lincoln

Lincoln, Nebraska, 68510, United States

Location

Omaha

Omaha, Nebraska, 68124, United States

Location

Las Vegas

Las Vegas, Nevada, 89106, United States

Location

Las Vegas

Las Vegas, Nevada, 89128, United States

Location

Lawrenceville

Lawrenceville, New Jersey, 08648, United States

Location

Albuquerque

Albuquerque, New Mexico, 87109, United States

Location

Williamsville

Williamsville, New York, 14221, United States

Location

Durham

Durham, North Carolina, 27713, United States

Location

Morehead City

Morehead City, North Carolina, 28557, United States

Location

Raleigh

Raleigh, North Carolina, 27612, United States

Location

Bismarck

Bismarck, North Dakota, 58501, United States

Location

Fargo

Fargo, North Dakota, 58103, United States

Location

Minot

Minot, North Dakota, 58701, United States

Location

Cincinnati

Cincinnati, Ohio, 45219, United States

Location

Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Dayton

Dayton, Ohio, 45409, United States

Location

Englewood

Englewood, Ohio, 45322, United States

Location

Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Bluffton

Bluffton, South Carolina, 29910, United States

Location

Charleston

Charleston, South Carolina, 29406, United States

Location

Columbia

Columbia, South Carolina, 29201, United States

Location

Greenville

Greenville, South Carolina, 29605, United States

Location

Chattanooga

Chattanooga, Tennessee, 37404, United States

Location

Memphis

Memphis, Tennessee, 38119, United States

Location

Memphis

Memphis, Tennessee, 38120, United States

Location

Fort Worth

Fort Worth, Texas, 76104, United States

Location

Houston

Houston, Texas, 77054, United States

Location

Houston

Houston, Texas, 77074, United States

Location

Irving

Irving, Texas, 75062, United States

Location

San Antonio

San Antonio, Texas, 78229, United States

Location

Sugar Land

Sugar Land, Texas, 77479, United States

Location

Webster

Webster, Texas, 77598, United States

Location

Salt Lake City

Salt Lake City, Utah, 84107, United States

Location

Salt Lake City

Salt Lake City, Utah, 84124, United States

Location

Norfolk

Norfolk, Virginia, 23507, United States

Location

Seattle

Seattle, Washington, 98105, United States

Location

Curitiba

Curitiba, 80430-160, Brazil

Location

Porto Alegre

Porto Alegre, 90510-040, Brazil

Location

Ribeirao Preto

Ribeirão Preto, 14049-900, Brazil

Location

Santo Andre

Santo André, 09190-510, Brazil

Location

Sao Paulo

São Paulo, 01317-000, Brazil

Location

Bologna

Bologna, 40138, Italy

Location

Catanzaro

Catanzaro, 88100, Italy

Location

Fiernze

Florence, 50134, Italy

Location

Genova

Genova, 16132, Italy

Location

Milano

Milan, 20132, Italy

Location

Modena

Modena, 41124, Italy

Location

Monserrato

Monserrato, 09042, Italy

Location

Napoli

Napoli, 80131, Italy

Location

Roma

Roma, 00161, Italy

Location

Roma

Roma, 00168, Italy

Location

Siena

Siena, 53100, Italy

Location

Torino

Torino, 10126, Italy

Location

Katowice

Katowice, 40-123, Poland

Location

Lodz

Lodz, 90-602, Poland

Location

Lodz

Lodz, 91-308, Poland

Location

Lublin

Lublin, 20-093, Poland

Location

Lublin

Lublin, 20-632, Poland

Location

Poznan

Poznan, 60-535, Poland

Location

Szczecin

Szczecin, 71-270, Poland

Location

Warszawa

Warsaw, 02-201, Poland

Location

Warszawa

Warsaw, 02-507, Poland

Location

Durban

Durban, 4052, South Africa

Location

Durban

Durban, 4126, South Africa

Location

Port Elizabeth

Port Elizabeth, 6001, South Africa

Location

Roodepoort

Roodepoort, 1724, South Africa

Location

Birmingham

Birmingham, B15 2TG, United Kingdom

Location

Isleworth

Isleworth, TW7 6AF, United Kingdom

Location

London

London, SE5 9NY, United Kingdom

Location

Nottingham

Nottingham, NG7 2FT, United Kingdom

Location

Related Publications (8)

• Stewart EA, Lukes AS, Venturella R, Ferreira JA, Li Y, Hunsche E, Wagman RB, Al-Hendy A. A plain language summary describing changes in pain associated with uterine fibroids among women receiving relugolix combination therapy. Pain Manag. 2024 Sep;14(9):469-476. doi: 10.1080/17581869.2024.2408114. Epub 2024 Oct 28.

  PMID: 39466126 DERIVED

• Stewart EA, Al-Hendy A, Lukes AS, Madueke-Laveaux OS, Zhu E, Proehl S, Schulmann T, Marsh EE. Relugolix combination therapy in Black/African American women with symptomatic uterine fibroids: LIBERTY Long-Term Extension study. Am J Obstet Gynecol. 2024 Feb;230(2):237.e1-237.e11. doi: 10.1016/j.ajog.2023.10.030. Epub 2023 Oct 18.

  PMID: 37863160 DERIVED

• Al-Hendy A, Lukes AS, Venturella R, Villarroel C, McKain L, Li Y, Wagman RB, Stewart EA. A plain language summary of the long-term relugolix combination therapy study for uterine fibroids. J Comp Eff Res. 2023 Aug;12(8):e230069. doi: 10.57264/cer-2023-0069. Epub 2023 Jul 21.

  PMID: 37477173 DERIVED

• Al-Hendy A, Lukes AS, Poindexter AN 3rd, Venturella R, Villarroel C, Critchley HO, Li Y, McKain L, Arjona Ferreira JC, Langenberg AG, Wagman RB, Stewart EA. A plain language summary of the safety of relugolix combination therapy and improvement in symptoms in women with uterine fibroids from the LIBERTY 1 and LIBERTY 2 studies. Pain Manag. 2023 Apr;13(4):205-211. doi: 10.2217/pmt-2022-0085. Epub 2023 May 15.

  PMID: 37183454 DERIVED

• Al-Hendy A, Lukes AS, Poindexter AN 3rd, Venturella R, Villarroel C, McKain L, Li Y, Wagman RB, Stewart EA. Long-term Relugolix Combination Therapy for Symptomatic Uterine Leiomyomas. Obstet Gynecol. 2022 Dec 1;140(6):920-930. doi: 10.1097/AOG.0000000000004988. Epub 2022 Nov 2.

  PMID: 36357960 DERIVED

• Stewart EA, Lukes AS, Venturella R, Arjona Ferreira JC, Li Y, Hunsche E, Wagman RB, Al-Hendy A. Relugolix Combination Therapy for Uterine Leiomyoma-Associated Pain in the LIBERTY Randomized Trials. Obstet Gynecol. 2022 Jun 1;139(6):1070-1081. doi: 10.1097/AOG.0000000000004787. Epub 2022 May 2.

  PMID: 35675604 DERIVED

• Hunsche E, Rakov V, Scippa K, Witherspoon B, McKain L. The Burden of Uterine Fibroids from the Perspective of US Women Participating in Open-Ended Interviews. Womens Health Rep (New Rochelle). 2022 Mar 4;3(1):286-296. doi: 10.1089/whr.2021.0086. eCollection 2022.

  PMID: 35415708 DERIVED

• Al-Hendy A, Lukes AS, Poindexter AN 3rd, Venturella R, Villarroel C, Critchley HOD, Li Y, McKain L, Arjona Ferreira JC, Langenberg AGM, Wagman RB, Stewart EA. Treatment of Uterine Fibroid Symptoms with Relugolix Combination Therapy. N Engl J Med. 2021 Feb 18;384(7):630-642. doi: 10.1056/NEJMoa2008283.

  PMID: 33596357 DERIVED

MeSH Terms

Conditions

Menorrhagia; Leiomyoma

Interventions

relugolix; estradiol, norethindrone drug combination; Estradiol

Condition Hierarchy (Ancestors)

Uterine Hemorrhage; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Menstruation Disturbances; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

None reported

Results Point of Contact

• Title: Clinical Trials at Myovant
• Organization: Myovant Sciences GmbH

clinicaltrials@myovant.com

+1 650 238 0250

Study Officials

• Myovant Medical Monitor

  Myovant Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2017
• First Posted: February 10, 2017
• Study Start: April 26, 2017
• Primary Completion: April 29, 2019
• Study Completion: August 24, 2020
• Last Updated: April 19, 2022
• Results First Posted: April 19, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (12); PL (9); ZA (4); BR (5); US (76); GB (4)