LIBERTY 2: Efficacy & Safety Study of Relugolix in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids

NCT ID: NCT03103087

Last Updated: 2022-04-20

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

382 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-06-14

Study Completion Date

2020-09-16

Brief Summary

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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.

Detailed Description

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This study is an international phase 3 randomized, double-blind, placebo-controlled efficacy and safety study to evaluate 24 weeks of oral daily relugolix 40 mg co-administered with low-dose E2 and NETA (Group A) and 12 weeks of daily oral relugolix 40 mg alone followed by 12 weeks of daily oral relugolix 40 mg co-administered with low-dose E2 and NETA (Group B) compared with 24 weeks of placebo (Group C).

All participants completing the Week 24 visit, including participants randomized to placebo, were offered the opportunity to enroll in an open-label extension study in which all eligible participants will receive relugolix co-administered with low-dose E2 and NETA. Participants who did not enroll into the extension study had a follow-up visit approximately 30 days after the end of treatment (that is, after the participant's last dose of study medication).

Safety will be assessed throughout the study by monitoring adverse events, vital signs, physical examinations, clinical laboratory tests, 12-lead electrocardiograms, and assessments of bone mineral density.

Conditions

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Heavy Menstrual Bleeding Uterine Fibroid

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Relugolix plus E2/NETA (Group A)

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

Group Type EXPERIMENTAL

Relugolix

Intervention Type DRUG

Relugolix (40 mg) tablet administered orally once daily.

Estradiol/norethindrone acetate

Intervention Type DRUG

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

Relugolix plus Delayed E2/NETA (Group B)

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

Group Type EXPERIMENTAL

Relugolix

Intervention Type DRUG

Relugolix (40 mg) tablet administered orally once daily.

Estradiol/norethindrone acetate

Intervention Type DRUG

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

Estradiol/norethindrone acetate placebo

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

Group Type PLACEBO_COMPARATOR

Relugolix placebo

Intervention Type DRUG

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

Estradiol/norethindrone acetate placebo

Intervention Type 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.

Interventions

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Relugolix

Relugolix (40 mg) tablet administered orally once daily.

Intervention Type DRUG

Estradiol/norethindrone acetate

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

Intervention Type DRUG

Relugolix placebo

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

Intervention Type DRUG

Estradiol/norethindrone acetate placebo

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.

Intervention Type DRUG

Other Intervention Names

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TAK-385 MVT-601 E2/NETA low-dose hormonal add-back E2/NETA placebo

Eligibility Criteria

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Inclusion Criteria

1. Premenopausal female aged 18 to 50 years old (inclusive) on the day of signing and dating the informed consent form.
2. 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.
3. Has a diagnosis of uterine fibroids that is confirmed by a transvaginal and/or transabdominal ultrasound performed during the screening period.
4. 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.

Exclusion Criteria

1. 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 participant's heavy menstrual bleeding.
2. Has known rapidly enlarging uterine fibroids in the opinion of the investigator.
3. 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.
4. 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.
5. 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.
6. Has been a participant in an investigational drug or device study within the 1 month prior to the first screening visit.
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Myovant Sciences GmbH

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Myovant Medical Monitor

Role: STUDY_DIRECTOR

Myovant Sciences

Locations

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Birmingham

Birmingham, Alabama, United States

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Mesa

Mesa, Arizona, United States

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Tucson

Tucson, Arizona, United States

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Tuscon

Tucson, Arizona, United States

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Canoga Park

Canoga Park, California, United States

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Huntington Beach

Huntington Beach, California, United States

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Long Beach

Long Beach, California, United States

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Los Angeles

Los Angeles, California, United States

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Los Angeles

Los Angeles, California, United States

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Panorama

Panorama City, California, United States

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San Diego

San Diego, California, United States

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Upland

Upland, California, United States

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Denver

Denver, Colorado, United States

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Lakewood

Lakewood, Colorado, United States

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Washington

Washington D.C., District of Columbia, United States

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Aventura

Aventura, Florida, United States

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DeLand

DeLand, Florida, United States

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Ft. Lauderdale

Fort Lauderdale, Florida, United States

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Jupiter

Jupiter, Florida, United States

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Lake City

Lake City, Florida, United States

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Loxahachee

Loxahatchee Groves, Florida, United States

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Miami

Miami, Florida, United States

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Miami

Miami, Florida, United States

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Miami Springs

Miami Springs, Florida, United States

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New Port Richey

New Port Richey, Florida, United States

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North Miami

North Miami, Florida, United States

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Oviedo

Oviedo, Florida, United States

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Plantation

Plantation, Florida, United States

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Port St. Lucie

Port Saint Lucie, Florida, United States

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Saint Cloud

Saint Cloud, Florida, United States

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Sarasota

Sarasota, Florida, United States

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Stuart

Stuart, Florida, United States

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Tampa

Tampa, Florida, United States

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Wellington

Wellington, Florida, United States

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West Palm Beach

West Palm Beach, Florida, United States

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Atlanta

Atlanta, Georgia, United States

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Decatur

Decatur, Georgia, United States

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Duluth

Duluth, Georgia, United States

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Norcross

Norcross, Georgia, United States

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Sandy Springs

Sandy Springs, Georgia, United States

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Savannah

Savannah, Georgia, United States

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Idaho Falls

Idaho Falls, Idaho, United States

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Nampa

Nampa, Idaho, United States

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Champaign

Champaign, Illinois, United States

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Chicago

Chicago, Illinois, United States

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Naperville

Naperville, Illinois, United States

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Oakbrook

Oak Brook, Illinois, United States

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Avon

Avon, Indiana, United States

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Shawnee

Shawnee Mission, Kansas, United States

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Marrero

Marrero, Louisiana, United States

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Metairie

Metairie, Louisiana, United States

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New Orleans

New Orleans, Louisiana, United States

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Baltimore

Baltimore, Maryland, United States

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Towson

Towson, Maryland, United States

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Bay City

Bay City, Michigan, United States

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Canton

Canton, Michigan, United States

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Detroit

Detroit, Michigan, United States

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Saginaw

Saginaw, Michigan, United States

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Norfolk

Norfolk, Nebraska, United States

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Las Vegas

Las Vegas, Nevada, United States

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Las Vegas

Las Vegas, Nevada, United States

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Las Vegas

Las Vegas, Nevada, United States

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New Brunswick

New Brunswick, New Jersey, United States

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Albuquerque

Albuquerque, New Mexico, United States

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Brooklyn

Brooklyn, New York, United States

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New York

New York, New York, United States

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New York

New York, New York, United States

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Rochester

Rochester, New York, United States

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Durham

Durham, North Carolina, United States

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Raleigh

Raleigh, North Carolina, United States

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Winston Salem

Winston-Salem, North Carolina, United States

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Cincinnati

Cincinnati, Ohio, United States

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Columbus

Columbus, Ohio, United States

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West Reading

West Reading, Pennsylvania, United States

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Charleston

Charleston, South Carolina, United States

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Beaumont

Beaumont, Texas, United States

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Dallas

Dallas, Texas, United States

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Dallas

Dallas, Texas, United States

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Fort Worth

Fort Worth, Texas, United States

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Frisco

Frisco, Texas, United States

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Houston

Houston, Texas, United States

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Houston

Houston, Texas, United States

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Longview

Longview, Texas, United States

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San Antonio

San Antonio, Texas, United States

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Virginia Beach

Norfolk, Virginia, United States

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Richmond

Richmond, Virginia, United States

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Covington

Covington, Washington, United States

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Puyallup

Puyallup, Washington, United States

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Spokane

Spokane, Washington, United States

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Brussels

Brussels, , Belgium

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Brussels

Brussels, , Belgium

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Ghent

Ghent, , Belgium

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Jette

Jette, , Belgium

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La Louvière

La Louvière, , Belgium

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Botucatu

Botucatu, , Brazil

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Porto Alegre

Porto Alegre, , Brazil

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Porto Alegre

Porto Alegre, , Brazil

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São Paulo

São Paulo, , Brazil

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Santiago

Santiago, Providencia, Chile

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San Ramon

San Ramón, , Chile

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Santiago

Santiago, , Chile

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Santiago

Santiago, , Chile

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Ceské Budejovice

České Budějovice, , Czechia

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Jihlava

Jihlava, , Czechia

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Nachod

Náchod, , Czechia

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Olomouc

Olomouc, , Czechia

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Ostrava

Ostrava, , Czechia

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Pisek

Písek, , Czechia

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Debrecen

Debrecen, Hajdu, Hungary

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Nyíregyháza

Nyíregyháza, Szabolcs-Szatmár-Bereg, Hungary

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Budapest

Budapest, , Hungary

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Debrecen

Debrecen, , Hungary

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Gyula

Gyula, , Hungary

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Kecskemét

Kecskemét, , Hungary

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Pecs

Pécs, , Hungary

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Szentes

Szentes, , Hungary

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Poznan

Poznan, Greater Poland Voivodeship, Poland

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Krakow

Krakow, Lesser Poland Voivodeship, Poland

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Rzeszów

Rzeszów, Masovian Voivodeship, Poland

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Białystok

Bialystok, Podlaskie Voivodeship, Poland

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Bialystok

Bialystok, Podlaskie Voivodeship, Poland

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Katowice

Katowice, Silesian Voivodeship, Poland

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Gdańsk

Gdansk, , Poland

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Cape Town

Cape Town, Western Cape, South Africa

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Bloemfontein

Bloemfontein, , South Africa

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Centurion

Centurion, , South Africa

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Parow

Parow, , South Africa

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Countries

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United States Belgium Brazil Chile Czechia Hungary Poland South Africa

References

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Catherino WH, Al-Hendy A, Zaim S, Bouzegaou N, Venturella R, Stewart EA, Wu R, Vannuccini S, Perry JS, Rakov VG, Munro MG. Efficacy and safety of relugolix combination therapy in women with uterine fibroids and adenomyosis: subgroup analysis of LIBERTY 1 and LIBERTY 2. Fertil Steril. 2025 Sep;124(3):523-533. doi: 10.1016/j.fertnstert.2025.04.037. Epub 2025 May 2.

Reference Type DERIVED
PMID: 40320117 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39466126 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37863160 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37477173 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37183454 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36357960 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35675604 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35415708 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33596357 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2016-005113-50

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MVT-601-3002

Identifier Type: -

Identifier Source: org_study_id

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