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Heavy Menstrual BleedingPhase 3NCT03049735

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

A Phase 3 study testing Relugolix and Estradiol/norethindrone acetate in people with Heavy Menstrual Bleeding and Uterine Fibroid, run by Myovant Sciences GmbH at 110 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 50 years, women only
Conditions the study is for
Heavy Menstrual Bleeding, Uterine Fibroid
What is being tested?
Relugolix and Estradiol/norethindrone acetate
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
388 participants
Where
110 sitesin 6 countries
Study dates
26 Apr 2017to 24 Aug 2020
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 50 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

110 sites in 6 countries.

110 sites in 6 countries

United States76 sites

  • Albuquerque

    Albuquerque, New Mexico, 87109

  • Andalusia

    Andalusia, Alabama, 36420

  • Atlanta

    Atlanta, Georgia, 30342

  • Atlanta

    Atlanta, Georgia, 49074

  • Augusta

    Augusta, Georgia, 30912

  • Aventura

    Aventura, Florida, 33180

  • Bismarck

    Bismarck, North Dakota, 58501

  • Bluffton

    Bluffton, South Carolina, 29910

  • Brandon

    Brandon, Florida, 33510

  • Charleston

    Charleston, South Carolina, 29406

  • Chattanooga

    Chattanooga, Tennessee, 37404

  • Cincinnati

    Cincinnati, Ohio, 45219

  • Cincinnati

    Cincinnati, Ohio, 45267

  • Clearwater

    Clearwater, Florida, 33759

  • Clermont

    Clermont, Florida, 34711

  • College Park

    College Park, Georgia, 30349

  • Columbia

    Columbia, South Carolina, 29201

  • Covington

    Covington, Louisiana, 70433

  • Dayton

    Dayton, Ohio, 45409

  • Denver

    Denver, Colorado, 80209

  • Durham

    Durham, North Carolina, 27713

  • Englewood

    Englewood, Ohio, 45322

  • Fargo

    Fargo, North Dakota, 58103

  • Fort Myers

    Fort Myers, Florida, 33912

  • Fort Worth

    Fort Worth, Texas, 76104

  • Greenville

    Greenville, South Carolina, 29605

  • Hialeah

    Hialeah, Florida, 33012

  • Hialeah

    Hialeah, Florida, 33016

  • Houston

    Houston, Texas, 77054

  • Houston

    Houston, Texas, 77074

  • Irving

    Irving, Texas, 75062

  • Jacksonville

    Jacksonville, Florida, 32207

  • La Mesa

    La Mesa, California, 91942

  • Lafayette

    Lafayette, Indiana, 47905

  • Las Vegas

    Las Vegas, Nevada, 89106

  • Las Vegas

    Las Vegas, Nevada, 89128

  • Lauderdale Lakes

    Lauderdale Lakes, Florida, 33319

  • Lawrenceville

    Lawrenceville, New Jersey, 08648

  • Lincoln

    Lincoln, Nebraska, 68510

  • Little Rock

    Little Rock, Arkansas, 72205

  • Lomita

    Lomita, California, 90717

  • Margate

    Margate, Florida, 33063

  • Memphis

    Memphis, Tennessee, 38119

  • Memphis

    Memphis, Tennessee, 38120

  • Miami

    Miami, Florida, 33155

  • Miami

    Miami, Florida, 33165

  • Miami

    Miami, Florida, 33176

  • Minot

    Minot, North Dakota, 58701

  • Mobile

    Mobile, Alabama, 36608

  • Morehead City

    Morehead City, North Carolina, 28557

  • Norfolk

    Norfolk, Virginia, 23507

  • Norwalk

    Norwalk, California, 90650

  • Oakbrook

    Oakbrook Terrace, Illinois, 60523

  • Oceanside

    Oceanside, California, 92056

  • Omaha

    Omaha, Nebraska, 68124

  • Orlando

    Orlando, Florida, 32806

  • Orlando

    Orlando, Florida, 32808

  • Palm Harbor

    Palm Harbor, Florida, 34684

  • Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Raleigh

    Raleigh, North Carolina, 27612

  • Richland

    Richland, Georgia, 99352

  • Salt Lake City

    Salt Lake City, Utah, 84107

  • Salt Lake City

    Salt Lake City, Utah, 84124

  • San Antonio

    San Antonio, Texas, 78229

  • San Diego

    San Diego, California, 92108

  • San Diego

    San Diego, California, 92111

  • Seattle

    Seattle, Washington, 98105

  • Shreveport

    Shreveport, Louisiana, 71118

  • South Miami

    South Miami, Florida, 33143

  • St. Louis

    St Louis, Missouri, 63141

  • Sugar Land

    Sugar Land, Texas, 77479

  • Tampa

    Tampa, Florida, 33613

  • Webster

    Webster, Texas, 77598

  • West Palm Beach

    West Palm Beach, Florida, 33409

  • Weston

    Weston, Florida, 33327

  • Williamsville

    Williamsville, New York, 14221

Other trials in United States

Italy12 sites

  • Bologna

    Bologna, 40138

  • Catanzaro

    Catanzaro, 88100

  • Fiernze

    Florence, 50134

  • Genova

    Genova, 16132

  • Milano

    Milan, 20132

  • Modena

    Modena, 41124

  • Monserrato

    Monserrato, 09042

  • Napoli

    Naples, 80131

  • Roma

    Roma, 00161

  • Roma

    Roma, 00168

  • Siena

    Siena, 53100

  • Torino

    Torino, 10126

Other trials in Italy

Poland9 sites

  • Katowice

    Katowice, 40-123

  • Lodz

    Lodz, 90-602

  • Lodz

    Lodz, 91-308

  • Lublin

    Lublin, 20-093

  • Lublin

    Lublin, 20-632

  • Poznan

    Poznan, 60-535

  • Szczecin

    Szczecin, 71-270

  • Warszawa

    Warsaw, 02-201

  • Warszawa

    Warsaw, 02-507

Other trials in Poland

Brazil5 sites

  • Curitiba

    Curitiba, 80430-160

  • Porto Alegre

    Porto Alegre, 90510-040

  • Ribeirao Preto

    Ribeirão Preto, 14049-900

  • Santo Andre

    Santo André, 09190-510

  • Sao Paulo

    São Paulo, 01317-000

Other trials in Brazil

South Africa4 sites

  • Durban

    Durban, 4052

  • Durban

    Durban, 4126

  • Port Elizabeth

    Port Elizabeth, 6001

  • Roodepoort

    Roodepoort, 1724

Other trials in South Africa

United Kingdom4 sites

  • Birmingham

    Birmingham, B15 2TG

  • Isleworth

    Isleworth, TW7 6AF

  • London

    London, SE5 9NY

  • Nottingham

    Nottingham, NG7 2FT

Other trials in United Kingdom

About this study

Official title: LIBERTY 1: An International Phase 3 Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study to Evaluate Relugolix Co-Administered With and Without Low-Dose Estradiol and Norethindrone Acetate in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids

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.

Read the detailed description

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 women 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.

Being tested
Relugolix, Estradiol/norethindrone acetate, Estradiol/norethindrone acetate placebo, Relugolix placebo
Keywords
Uterine Fibroid, Heavy Menstrual Bleeding, Menstrual Blood Volume
Medical subject headings
Menorrhagia, Leiomyoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RelugolixDrug

    Also called TAK-385, MVT-601

    Relugolix (40 mg) tablet administered orally once daily.

  • Estradiol/norethindrone acetateDrug

    Also called E2/NETA, low-dose hormonal add-back

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

  • Estradiol/norethindrone acetate placeboDrug

    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.

  • Relugolix placeboDrug

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

Study groups in NCT03049735
Study groupRoleWhat they receive
Relugolix plus E2/NETA (Group A)ExperimentalRelugolix co-administered with E2/NETA for 24 weeks.
Receives: Drug: Relugolix; Drug: Estradiol/norethindrone acetate
Relugolix plus Delayed E2/NETA (Group B)ExperimentalRelugolix co-administered with E2/NETA placebo for 12 weeks, followed by relugolix co-administered with E2/NETA for 12 weeks.
Receives: Drug: Relugolix; Drug: Estradiol/norethindrone acetate; Drug: Estradiol/norethindrone acetate placebo
Placebo (Group C)Placebo comparatorRelugolix placebo co-administered with E2/NETA placebo for 24 weeks.
Receives: Drug: Estradiol/norethindrone acetate placebo; Drug: Relugolix placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (43)

  1. Percentage Of Participants With Amenorrhea Over The Last 35 Days Of Treatment

    Amenorrhea was defined as meeting 1 of the following criteria for 2 consecutive visits:

    1. No feminine product returned due to reported amenorrhea;
    2. No feminine product returned due to reports of spotting/negligible bleeding coupled with electronic diary (eDiary) data indicating infrequent non-cyclic bleeding/spotting;
    3. Feminine product collection with a negligible observed MBL volume coupled with eDiary data indicating infrequent non-cyclic bleeding/spotting.

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

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

  2. Percent Change From Baseline At Week 24 In MBL Volume

    MBL volume was measured using the alkaline hematin method. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: Baseline, Week 24

  3. 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

    Blood samples were collected from participants for hemoglobin measurements. Percentages are based on number of participants with hemoglobin ≤ 10.5 gram (g)/deciliter (dL) at Baseline and reported at Week 24.

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA with placebo arms are presented.

    Measured: From Baseline up to Week 24

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

    Uterine fibroid-associated pain was assessed by a pain numerical rating scale (NRS). The pain NRS is a validated, single-item, self-reported measure, which asks respondents to rank their pain on an 11-point scale as follows: 0 (no pain), 1 to 3 (mild pain), 4 to 6 (moderate pain), and 7 to 10 (severe pain).

    Participants were asked to document, in an e-Diary, the worst pain associated with their uterine fibroids that they experienced during the last 24 hours, every day until the end of study drug administration. Pain evaluable participants, defined as those who had maximum NRS score ≥ 4 at Baseline and had at least 28 days (80% of the last 35 days of treatment) of pain scores recorded in the e-Diary, were analyzed.

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: From Baseline up to Week 24

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

    The volume of the primary uterine fibroid was measured by transvaginal or transabdominal ultrasound.

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: Baseline, Week 24

  6. Percent Change From Baseline At Week 24 In Uterine Volume

    The volume of the uterus was measured by transvaginal or transabdominal ultrasound.

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: Baseline, Week 24

  7. Change From Baseline At Week 24 In UFS-QoL Bleeding And Pelvic Discomfort Scale Score As Measured By The UFS-QoL (Q1, Q2, Q5)

    The Uterine Fibroid Symptom and Health-Related Quality of Life (UFS-QoL) Bleeding and Pelvic Discomfort (BPD) Scale has been derived from the UFS-QoL Symptoms Scale. The scale consists of the following 3 symptoms proximal to uterine fibroids: Heavy bleeding during your menstrual period (Question [Q] 1), passing blood clots during your menstrual period (Q2), and feeling tightness or pressure in your pelvic area (Q5). raw scores were transformed to a normalized score: Transformed Score = [(Actual raw score - lowest possible raw score)/(Possible raw score range)] * 100 Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity.

    As per the study objective, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only these two arms are presented.

    Measured: Baseline, Week 24

  8. Percent Change From Baseline At Week 12 In Bone Mineral Density At The Lumbar Spine (L1 To L4), As Assessed By DXA

    Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry (DXA) at the lumbar spine (L1, L2, L3, and L4) at Baseline and at Week 12. The scans were read by the central radiology laboratory in accordance with the imaging charter. The same DXA machine was used at the local imaging center at each site and operated in the same scan mode for all images procured for an individual participant. All images were submitted for central reading. The central radiology laboratory collected and evaluated all DXA scans for acceptability and measured BMD.

    As per the objective of the study, the pre-specified secondary analyses compared relugolix plus E2/NETA with relugolix plus delayed E2/NETA at Week 12 and are presented below.

    Measured: Baseline, Week 12

  9. Percent Change From Baseline At Week 24 In Bone Mineral Density At The Lumbar Spine (L1 To L4), Total Hip, And Femoral Neck

    BMD was assessed by DXA at the lumbar spine (L1, L2, L3, and L4), total hip, and femoral neck at Baseline and at Week 24. The scans were read by the central radiology laboratory in accordance with the imaging charter. The same DXA machine was used at the local imaging center at each site and operated in the same scan mode for all images procured for an individual participant. All images were submitted for central reading. The central radiology laboratory collected and evaluated all DXA scans for acceptability and measured BMD.

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: Baseline, Week 24

  10. Percentage Of Participants Experiencing Vasomotor Symptoms Through Week 12

    An adverse event was defined as an unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product, whether or not related to the medicinal product. The preferred terms of hyperhidrosis, feeling hot, hot flush, night sweats, and flushing were combined to describe vasomotor symptoms. Participants with multiple events for a given preferred term were counted only once for each preferred term.

    Reported CI based on exact binomial 95% CI (Clopper-Pearson).

    As per the objective of the study, this secondary analysis compared relugolix plus E2/NETA with relugolix plus delayed E2/NETA at Week 12 and are presented below.

    Measured: Baseline through Week 12

  11. Percentage Of Participants Experiencing Vasomotor Symptoms Through Week 24

    An adverse event was defined as an unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product, whether or not related to the medicinal product. The preferred terms of hyperhidrosis, feeling hot, hot flush, night sweats, and flushing were combined to describe vasomotor symptoms. Participants with multiple events for a given preferred term were counted only once for each preferred term.

    Reported percentages based on the total number of participants in each treatment group.

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: Baseline through Week 24

  12. Predose Trough Concentrations Of Relugolix And Norethindrone (NET) In The Relugolix Plus E2/NETA Group At Week 24

    Blood samples for determination of relugolix and NET plasma concentrations were collected predose at Week 24. Relugolix and NET plasma concentrations were determined using validated bioanalytical methodology.

    Concentrations below the quantification limit (BQL) were set to 0 for analysis of summary statistics.

    As per the objective of the study, only relugolix plus E2/NETA concentration is presented.

    Measured: Week 24

  13. Predose Trough Concentrations Of E2 In The Relugolix Plus E2/NETA Group At Week 24

    Blood samples for determination of E2 serum concentrations were collected predose at Week 24. Relugolix and NET plasma concentrations were determined using validated bioanalytical methodology.

    Concentrations below the quantification limit (BQL) were set to 0 for analysis of summary statistics. As per the objective of the study, only relugolix plus E2/NETA concentration is presented.

    Measured: Week 24

  14. Change From Baseline At Week 24 In Predose Concentrations Of Estradiol In The Relugolix Plus E2/NETA Group

    Blood samples for determination of serum concentrations were collected predose at Week 24. Relugolix and NET plasma concentrations were determined using validated bioanalytical methodology.

    Concentrations below the quantification limit (BQL) were set to 0 for analysis of summary statistics. As per the objective of the study, only relugolix plus E2/NETA concentration is presented.

    Measured: Baseline, Week 24

  15. Time To MBL Response

    Defined as the time to achieve an MBL volume of < 80 mL and a ≥ 50% reduction from Baseline MBL volume as measured by the alkaline hematin method. MBL volume was measured using the alkaline hematin method.

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: From Baseline through Week 24

  16. Sustained Amenorrhea Rate (No Or Negligible Bleeding)

    Sustained amenorrhea is defined as participants time to achieve and maintain amenorrhea until the date of last study drug.

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: Week 24

  17. Time To Achieving Sustained Amenorrhea (No Or Negligible Bleeding)

    Sustained amenorrhea status as determined based on time to achieve and maintain amenorrhea status.

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: From Baseline through Week 24

  18. Time To Achieving Amenorrhea (No Or Negligible Bleeding)

    Time to amenorrhea was defined as the weeks from date of first dose of study drug to the start of amenorrhea.

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: From Baseline through Week 24

  19. Number Of Participants With Hemoglobin ≤ 10.5 g/dL At Baseline And Achieved An Increase Of > 2 g/dL At Week 24

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: From Baseline through Week 24

  20. Percent Change From Baseline In Hemoglobin For Women With a Hemoglobin ≤ 10.5 g/dL At Baseline

    LS means and p-value for test of difference is relugolix plus E2/NETA minus Placebo based on mixed-effect model with treatment, visit, region, Baseline MBL and treatment by visit interaction included as fixed effects.

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: Week 24

  21. Number Of Participants With Hemoglobin Increase Of ≥ 1 g/dL From Baseline To Week 24 Among Those With Below Lower Limit Of Normal

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: Week 24

  22. Change From Baseline At Week 24 In The UFS-QoL Symptom Severity Scale Score

    Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity. A negative change from baseline indicates improvement.

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: Baseline, Week 24

  23. Change From Baseline At Week 24 In The UFS-QoL Activities Scale Score

    Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity.

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: Baseline, Week 24

  24. Change From Baseline At Week 24 In The UFS-QoL Revised Activities Scale Score

    Transformed score ranges from 0 to 100 based on Likert scale (none of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity.

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: Baseline, Week 24

  25. Change From Baseline In UFS-QoL Score By Health-Related Quality Of Life Total Score

    The UFS-QoL total score was the sum of 6 subscales (concern, activities, energy/mood, control, self-conscious, and sexual function). The raw scores were transformed to normalized scores. Transformed score ranges from 0 to 100. Higher scores are indicative of better health-related quality of life (high = good).

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: Baseline, Week 24

  26. Number Of Responders With At Least 20 Points Increase From Baseline At Week 24 In UFS-QoL Revised Activities Scale Score

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: From Baseline through Week 24

  27. Change From Baseline In UFS-QoL Bleeding And Pelvic Discomfort Scale Score

    The Bleeding and Pelvic Discomfort Scale consists of 3 items proximal to uterine fibroids that are experienced by most patients (heavy bleeding during the menstrual period [Question 1], passing blood clots during the menstrual period [Question 2], and feeling tightness or pressure in the pelvic area [Question 5]).Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity. A negative change from baseline indicates improvement.

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: Baseline, Week 24

  28. Number Of Responders With At Least 20 Points Decrease In UFS-QoL Bleeding And Pelvic Discomfort Scale Score

    A Responder was defined as meeting a meaningful change threshold, set as a 20-point change from Baseline, in the Bleeding And Pelvic Discomfort Scale at Week 24 on the transformed score.

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: Baseline, Week 24

  29. Change From Baseline At Week 24 In The Interference Of Uterine Fibroids With Physical Activities Based On UFS-QoL Question 11

    Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity. A negative change from baseline indicates improvement.

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: Baseline, Week 24

  30. Change From Baseline At Week 24 In The Interference Of Uterine Fibroids With Social Activities Based On UFS-QoL Question 20

    Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity. A negative change from baseline indicates improvement.

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: Baseline, Week 24

  31. Change From Baseline At Week 24 In Embarrassment Caused By Uterine Fibroids Based On UFS-QoL Question 29

    Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity. A negative change from baseline indicates improvement.

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: Baseline, Week 24

  32. Change From Baseline At Week 24 In Symptoms Assessed Using The Patient Global Assessment (PGA) Questionnaire

    The PGAs assessed participants' limitation in activities and the severity of symptoms due to uterine fibroids over the previous 4 weeks, as perceived by the participant. The PGA for symptoms is a 1-item questionnaire designed to assess participant's impression of the severity of their symptoms related to uterine fibroids. The PGA for function and symptoms was evaluated using a 5-point response scale (no limitation at all [1], mild limitation [2], moderate limitation [3], quite a bit of limitation [4], and extreme limitation [5]).

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: Baseline, Week 24

  33. Change From Baseline At Week 24 In Function Assessed Using The PGA Questionnaire

    The PGAs assessed participants' limitation in activities and the severity of symptoms due to uterine fibroids over the previous 4 weeks, as perceived by the participant. The PGA for symptoms is a 1-item questionnaire designed to assess participant's impression of the severity of their symptoms related to uterine fibroids. The PGA for function and symptoms was evaluated using a 5-point response scale (no limitation at all [1], mild limitation [2], moderate limitation [3], quite a bit of limitation [4], and extreme limitation [5]).

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: Baseline, Week 24

  34. Participants Achieving Improvement From Baseline In The PGA Questionnaire For Symptoms From Baseline At Week 24

    The PGAs assessed participants' limitation in activities and the severity of symptoms due to uterine fibroids over the previous 4 weeks, as perceived by the participant. The PGA for function and symptoms was evaluated using a 5-point response scale (no limitation at all [1], mild limitation [2], moderate limitation [3], quite a bit of limitation [4], and extreme limitation [5]). Category improvements for symptoms are presented. A 1-category improvement would be severe at baseline to moderate.

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: From Baseline through Week 24

  35. Participants Achieving Improvement From Baseline In The PGA Questionnaire For Uterine Fibroid-related Function From Baseline At Week 24

    The PGAs assessed participants' limitation in activities and the severity of symptoms due to uterine fibroids over the previous 4 weeks, as perceived by the participant. The PGA for function and symptoms was evaluated using a 5-point response scale (no limitation at all [1], mild limitation [2], moderate limitation [3], quite a bit of limitation [4], and extreme limitation [5]). Category improvements for symptoms are presented. A 1-category improvement would be severe at baseline to moderate.

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: From Baseline through Week 24

  36. Change From Baseline At Week 24 In The Menorrhagia Impact Questionnaire Score For Physical Activities

    The Menorrhagia Impact was evaluated using a 5-point response scale to assess level of improvement from Baseline to Week 24. Response scale: Not at all, 2. Slightly, 3.Moderately, 4. Quite a bit and 5. Extremely.

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: Baseline, Week 24

  37. Change From Baseline At Week 24 In The Menorrhagia Impact Questionnaire Score For Social Activities

    The Menorrhagia Impact was evaluated using a 5-point response scale to assess level of improvement from Baseline to Week 24. Response scale: Not at all, 2. Slightly, 3.Moderately, 4. Quite a bit and 5. Extremely.

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: Baseline, Week 24

  38. Number Of Participants Who Achieved A Maximum NRS Score ≤ 1 For Uterine Fibroid-associated Pain Over The Last 35 Days Of Treatment Who Had Maximum Pain Scores ≥ 4 During The 35 Days Prior To Randomization

    Uterine fibroid-associated pain was assessed by a pain NRS. The pain NRS is a validated, single-item, self-reported measure, which asks respondents to rank their pain on an 11-point scale as follows: 0 (no pain), 1 to 3 (mild pain), 4 to 6 (moderate pain), and 7 to 10 (severe pain).

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: From Baseline up to the last 35 days of treatment (up to 24 weeks)

  39. Number Of Participants With A ≥ 30% Reduction in NRS Score From Baseline to Last 35 Days of Treatment Who Had Maximum Pain Scores ≥ 4 At Baseline

    Uterine fibroid-associated pain was assessed by a pain NRS. The pain NRS is a validated, single-item, self-reported measure, which asks respondents to rank their pain on an 11-point scale as follows: 0 (no pain), 1 to 3 (mild pain), 4 to 6 (moderate pain), and 7 to 10 (severe pain).

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: Baseline, Week 24

  40. Change From Baseline In Luteinizing Serum Concentration At Week 24

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: Baseline, Week 24

  41. Change From Baseline In Follicle Stimulating Serum Concentration At Week 24

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: Baseline, Week 24

  42. Change From Baseline In E2 Serum Concentration At Week 24

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: Baseline, Week 24

  43. Change From Baseline In Progesterone Serum Concentration At Week 24

    As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

    Measured: Baseline, Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Feb 2017
  2. Study start26 Apr 2017
  3. Primary completion29 Apr 2019
  4. Study completion24 Aug 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
388 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03049735
Sponsor's protocol ID
MVT-601-3001
Other IDs
2016-003727-27, 2016
Status last verified
Mar 2022
First submitted
8 Feb 2017
Last updated
19 Apr 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 39466126

  • 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.

    PubMed 37863160

  • 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.

    PubMed 37477173

  • 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.

    PubMed 37183454

  • 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.

    PubMed 36357960

  • 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.

    PubMed 35675604

  • 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.

    PubMed 35415708

  • 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.

    PubMed 33596357

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Relugolix and Estradiol/norethindrone acetate in people with Heavy Menstrual Bleeding and Uterine Fibroid, run by Myovant Sciences GmbH at 110 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 110 sites in United States, Italy, Poland, Brazil, South Africa and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: From Baseline up to last 35 days of treatment (up to Week 24)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03049735, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2022.

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