Heavy Menstrual BleedingPhase 3NCT03103087
LIBERTY 2: 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 127 sites in 8 countries.
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
- 382 participants
- Where
- 127 sitesin 8 countries
- Study dates
- 14 Jun 2017to 16 Sep 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 participant'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
127 sites in 8 countries.
127 sites in 8 countries
United States89 sites
Albuquerque
Albuquerque, New Mexico, 87102
Atlanta
Atlanta, Georgia, 30312
Aventura
Aventura, Florida, 33180
Avon
Avon, Indiana, 46123
Baltimore
Baltimore, Maryland, 21208
Bay City
Bay City, Michigan, 48706
Beaumont
Beaumont, Texas, 77702
Birmingham
Birmingham, Alabama, 35205
Brooklyn
Brooklyn, New York, 11201
Canoga Park
Canoga Park, California, 91303
Canton
Canton, Michigan, 48187
Champaign
Champaign, Illinois, 61820
Charleston
Charleston, South Carolina, 29406
Chicago
Chicago, Illinois, 60611
Cincinnati
Cincinnati, Ohio, 45212
Columbus
Columbus, Ohio, 43231
Covington
Covington, Washington, 98042
Dallas
Dallas, Texas, 75231
Dallas
Dallas, Texas, 75234
Decatur
Decatur, Georgia, 30034
DeLand
DeLand, Florida, 32720
Denver
Denver, Colorado, 80209
Detroit
Detroit, Michigan, 48201
Duluth
Duluth, Georgia, 30097
Durham
Durham, North Carolina, 27713
Ft. Lauderdale
Fort Lauderdale, Florida, 33316
Fort Worth
Fort Worth, Texas, 76104
Frisco
Frisco, Texas, 75035
Houston
Houston, Texas, 77030
Houston
Houston, Texas, 77054
Huntington Beach
Huntington Beach, California, 92647
Idaho Falls
Idaho Falls, Idaho, 83404
Jupiter
Jupiter, Florida, 33458
Lake City
Lake City, Florida, 32055
Lakewood
Lakewood, Colorado, 80228
Las Vegas
Las Vegas, Nevada, 89106
Las Vegas
Las Vegas, Nevada, 89109
Las Vegas
Las Vegas, Nevada, 89113
Long Beach
Long Beach, California, 90806
Longview
Longview, Texas, 75605
Los Angeles
Los Angeles, California, 90036
Los Angeles
Los Angeles, California, 90057
Loxahachee
Loxahatchee Groves, Florida, 33470
Marrero
Marrero, Louisiana, 70072
Mesa
Mesa, Arizona, 85209
Metairie
Metairie, Louisiana, 70006
Miami
Miami, Florida, 33126
Miami
Miami, Florida, 33155
Miami Springs
Miami Springs, Florida, 33166
Nampa
Nampa, Idaho, 83686
Naperville
Naperville, Illinois, 60540
New Brunswick
New Brunswick, New Jersey, 08901
New Orleans
New Orleans, Louisiana, 70115
New Port Richey
New Port Richey, Florida, 34652
New York
New York, New York, 10022
New York
New York, New York, 10038
Norcross
Norcross, Georgia, 30093
Norfolk
Norfolk, Nebraska, 68701
Virginia Beach
Norfolk, Virginia, 23502
North Miami
North Miami, Florida, 33161
Oakbrook
Oak Brook, Illinois, 60523
Oviedo
Oviedo, Florida, 32765
Panorama
Panorama City, California, 91402
Plantation
Plantation, Florida, 33324
Port St. Lucie
Port Saint Lucie, Florida, 34952
Puyallup
Puyallup, Washington, 98372
Raleigh
Raleigh, North Carolina, 27607
Richmond
Richmond, Virginia, 23225
Rochester
Rochester, New York, 14642
Saginaw
Saginaw, Michigan, 48604
Saint Cloud
Saint Cloud, Florida, 34769
San Antonio
San Antonio, Texas, 78258
San Diego
San Diego, California, 92114
Sandy Springs
Sandy Springs, Georgia, 30328
Sarasota
Sarasota, Florida, 34239
Savannah
Savannah, Georgia, 31406
Shawnee
Shawnee Mission, Kansas, 66128
Spokane
Spokane, Washington, 99207
Stuart
Stuart, Florida, 34996
Tampa
Tampa, Florida, 33606
Towson
Towson, Maryland, 21204
Tucson
Tucson, Arizona, 85704
Tuscon
Tucson, Arizona, 85712
Upland
Upland, California, 91786
Washington
Washington D.C., District of Columbia, 20036
Wellington
Wellington, Florida, 33414
West Palm Beach
West Palm Beach, Florida, 33409
West Reading
West Reading, Pennsylvania, 19611
Winston Salem
Winston-Salem, North Carolina, 27103
Hungary8 sites
Budapest
Budapest, 1106
Debrecen
Debrecen, Hajdu, 4032
Debrecen
Debrecen, 4025
Gyula
Gyula, 5700
Kecskemét
Kecskemét, 6000
Nyíregyháza
Nyíregyháza, Szabolcs-Szatmár-Bereg, 4400
Pecs
Pécs, 7624
Szentes
Szentes, 6600
Poland7 sites
Białystok
Bialystok, Podlaskie Voivodeship, 15224
Bialystok
Bialystok, Podlaskie Voivodeship, 15464
Gdańsk
Gdansk, 80850
Katowice
Katowice, Silesian Voivodeship, 40724
Krakow
Krakow, Lesser Poland Voivodeship, 30114
Poznan
Poznan, Greater Poland Voivodeship, 60-192
Rzeszów
Rzeszów, Masovian Voivodeship, 35302
Czechia6 sites
Ceské Budejovice
České Budějovice, 370 01
Jihlava
Jihlava, 586 33
Nachod
Náchod, 54701
Olomouc
Olomouc, 772 00
Ostrava
Ostrava, 708 52
Pisek
Písek, 39701
Belgium5 sites
Brussels
Brussels, 1070
Brussels
Brussels, 1200
Ghent
Ghent, 9000
Jette
Jette, 1090
La Louvière
La Louvière, 7100
Brazil4 sites
Botucatu
Botucatu, 18618-686
Porto Alegre
Porto Alegre, 90035-903
Porto Alegre
Porto Alegre, 90510-040
São Paulo
São Paulo, 04266-010
Chile4 sites
San Ramon
San Ramón, 8880465
Santiago
Santiago, Providencia, 7510186
Santiago
Santiago, 8320165
Santiago
Santiago, 8360160
South Africa4 sites
Bloemfontein
Bloemfontein, 9301
Cape Town
Cape Town, Western Cape, 7405
Centurion
Centurion, 00157
Parow
Parow, 7500
About this study
Official title: LIBERTY 2: 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 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
- Heavy Menstrual Bleeding, Uterine Fibroid
- Being tested
- Relugolix, Estradiol/norethindrone acetate, Relugolix placebo, Estradiol/norethindrone acetate 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.
Relugolix placeboDrug
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 placeboDrug
Also called E2/NETA 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.
| Study group | Role | What they receive |
|---|---|---|
| Relugolix plus E2/NETA (Group A) | Experimental | Relugolix co-administered with E2/NETA for 24 weeks. Receives: 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. Receives: 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. Receives: Drug: Relugolix placebo; Drug: Estradiol/norethindrone acetate placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 the last 35 days of treatment (up to Week 24)
Secondary outcomes (43)
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:
- No feminine product returned due to reported amenorrhea;
- No feminine product returned due to reports of spotting/negligible bleeding coupled with electronic diary (e-Diary) data indicating infrequent non-cyclic bleeding/spotting;
- Feminine product collection with a negligible observed MBL volume coupled with e-Diary 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)
Percent Change From Baseline At Week 24 In MBL Volume
MBL volume was measured using the alkaline hematin method. Least square (LS) means 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: 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
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
Percentage Of Participants With A Maximum Numerical Rating Scale (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
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
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: From Baseline up to Week 24
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 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
Measured: Baseline Week 24
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. The LS means were based on a mixed-effect model with visit, region, Baseline MBL volume, age at Baseline, body mass index at Baseline, BMD at Baseline, race, 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: From Baseline up to Week 12
Percent Change From Baseline At Week 24 In Bone Mineral Density At The Lumbar Spine (L1 To L4), Total Hip, And Femoral Neck As Assessed By DXA
BMD was assessed by DXA at the lumbar spine (L1, L2, L3, and L4), total hip, and femoral neck (same leg across participants) 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. The LS means were based on a mixed-effect model with visit, region, Baseline MBL volume, age at Baseline, body mass index at Baseline, BMD at Baseline, race, and treatment by visit interaction included as fixed effects. For Relugolix plus E2/NETA Lumbar Spine (L1 to L4), number (n)=95.
As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only rel
Measured: Baseline through Week 24
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 confidence interval (CI) based on exact binomial 95% CI (Clopper-Pearson). As per the objective of the study, the 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
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
Predose Trough Concentrations Of Relugolix And 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
Predose Trough Concentrations Of E2 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
Change From Baseline At Week 24 In Predose Concentrations Of E2 In The Relugolix Plus E2/NETA Group
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: Baseline, Week 24
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.
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
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
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
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
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
Percent Change From Baseline At Week 24 In Hemoglobin For Women With A Hemoglobin Concentration ≤ 10.5 g/dL At Baseline
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
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
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 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
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). Higher scores are indicative of better health-related quality of life (high score = 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
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). Higher scores are indicative of better health-related quality of life (high score = good). LS means and p-value for test of difference was 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: Baseline, Week 24
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
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
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 participants (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
Number Of Responders With At Least 20 Points Decrease in UFS-QoL Bleeding And Pelvic Discomfort Scale Score
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
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
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
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
Change From Baseline At Week 24 In Symptoms Assessed Using The Patient Global Assessment (PGA) Questionnaire
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
Change From Baseline At Week 24 In Function Assessed Using The PGA Questionnaire
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
Participants Achieving Improvement From Baseline In 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
Participants Achieving Improvement From Baseline In PGA 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
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
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
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)
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
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
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
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
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.
- First posted6 Apr 2017
- Study start14 Jun 2017
- Primary completion10 Jul 2019
- Study completion16 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Heavy Menstrual BleedingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 382 participants (actual)
Sponsor and investigators
- Lead sponsor
- Myovant Sciences GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Myovant Medical Monitor, Study director, Myovant Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03103087
- Sponsor's protocol ID
- MVT-601-3002
- Other IDs
- 2016-005113-50, 2016
- Status last verified
- Sep 2021
- First submitted
- 8 Feb 2017
- Last updated
- 20 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 40320117Stewart 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 39466126Stewart 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 37863160Al-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 37477173Al-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 37183454Al-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 36357960Stewart 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 35675604Hunsche 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 35415708Al-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
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- LIBERTY 2: 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
- ClinicalTrials.gov ID
- NCT03103087
- Acronym / sponsor ID
- MVT-601-3002
- Conditions
- Heavy Menstrual Bleeding, Uterine Fibroid
- Keywords
- Uterine Fibroid, Heavy Menstrual Bleeding, Menstrual Blood Volume
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 382 participants (actual)
- Lead sponsor
- Myovant Sciences GmbHIndustry (pharma, biotech, devices)
- Study start
- 14 Jun 2017 (actual)
- Primary completion
- 10 Jul 2019 (actual)
- Study completion
- 16 Sep 2020 (actual)
- First posted
- 6 Apr 2017 (actual)
- Results
- Posted 20 Apr 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Relugolix plus E2/NETA (Group A) | Experimental | Drug: Relugolix, Drug: Estradiol/norethindrone acetateRelugolix co-administered with E2/NETA for 24 weeks. |
| Relugolix plus Delayed E2/NETA (Group B) | Experimental | Drug: Relugolix, Drug: Estradiol/norethindrone acetate, Drug: Estradiol/norethindrone acetate placeboRelugolix co-administered with E2/NETA placebo for 12 weeks, followed by relugolix co-administered with E2/NETA for 12 weeks. |
| Placebo (Group C) | Placebo comparator | Drug: Relugolix placebo, Drug: Estradiol/norethindrone acetate placeboRelugolix placebo co-administered with E2/NETA placebo for 24 weeks. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RelugolixAlso: TAK-385, MVT-601Relugolix (40 mg) tablet administered orally once daily. | Drug | Relugolix plus Delayed E2/NETA (Group B), Relugolix plus E2/NETA (Group A) |
| Estradiol/norethindrone acetateAlso: E2/NETA, low-dose hormonal add-backE2 (1.0 mg)/NETA (0.5 mg) co-formulated capsule administered orally once daily. | Drug | Relugolix plus Delayed E2/NETA (Group B), Relugolix plus E2/NETA (Group A) |
| Relugolix placeboRelugolix (0 mg) placebo tablet administered orally once daily and manufactured to match the relugolix tablet in size, shape, color, and odor. | Drug | Placebo (Group C) |
| Estradiol/norethindrone acetate placeboAlso: E2/NETA placeboE2 (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. | Drug | Placebo (Group C), Relugolix plus Delayed E2/NETA (Group B) |
Primary outcome
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 the last 35 days of treatment (up to Week 24)
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.
43 secondary outcomes
Percentage Of Participants With Amenorrhea Over The Last 35 Days Of Treatment
Time frame: From Baseline up to last 35 days of treatment (up to Week 24)
Percent Change From Baseline At Week 24 In MBL Volume
Time frame: 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
Time frame: From Baseline up to Week 24
Percentage Of Participants With A Maximum Numerical Rating Scale (NRS) Score ≤ 1 For Uterine Fibroid-Associated Pain Over The Last 35 Days Of Treatment
Time frame: From Baseline up to Week 24
Percent Change From Baseline At Week 24 In Primary Uterine Fibroid Volume
Time frame: Baseline Week 24
Percent Change From Baseline At Week 24 In Uterine Volume
Time frame: From Baseline up to Week 24
Change From Baseline At Week 24 In UFS-QoL Bleeding And Pelvic Discomfort Scale Score As Measured By The UFS-QoL (Q1, Q2, Q5)
Time frame: Baseline Week 24
Percent Change From Baseline At Week 12 In Bone Mineral Density At The Lumbar Spine (L1 to L4) As Assessed By DXA
Time frame: From Baseline up to Week 12
Percent Change From Baseline At Week 24 In Bone Mineral Density At The Lumbar Spine (L1 To L4), Total Hip, And Femoral Neck As Assessed By DXA
Time frame: Baseline through Week 24
Percentage Of Participants Experiencing Vasomotor Symptoms Through Week 12
Time frame: Baseline through Week 12
Percentage Of Participants Experiencing Vasomotor Symptoms Through Week 24
Time frame: Baseline through Week 24
Predose Trough Concentrations Of Relugolix And NET In The Relugolix Plus E2/NETA Group At Week 24
Time frame: Week 24
Predose Trough Concentrations Of E2 In The Relugolix Plus E2/NETA Group At Week 24
Time frame: Week 24
Change From Baseline At Week 24 In Predose Concentrations Of E2 In The Relugolix Plus E2/NETA Group
Time frame: Baseline, Week 24
Time To MBL Response
Time frame: From Baseline through Week 24
Sustained Amenorrhea Rate (No Or Negligible Bleeding)
Time frame: Week 24
Time To Achieving Sustained Amenorrhea (No Or Negligible Bleeding)
Time frame: From Baseline through Week 24
Time To Achieving Amenorrhea (No Or Negligible Bleeding)
Time frame: From Baseline through Week 24
Number Of Participants With Hemoglobin ≤ 10.5 g/dL At Baseline And Achieved An Increase Of > 2 g/dL At Week 24
Time frame: From Baseline through Week 24
Percent Change From Baseline At Week 24 In Hemoglobin For Women With A Hemoglobin Concentration ≤ 10.5 g/dL At Baseline
Time frame: Baseline, Week 24
Number Of Participants With Hemoglobin Increase Of ≥ 1 g/dL From Baseline To Week 24 Among Those With Below Lower Limit Of Normal
Time frame: Week 24
Change From Baseline At Week 24 In The UFS-QoL Symptom Severity Scale Score
Time frame: Baseline, Week 24
Change From Baseline At Week 24 In The UFS-QoL Activities Scale Score
Time frame: Baseline, Week 24
Change From Baseline At Week 24 In The UFS-QoL Revised Activities Scale Score
Time frame: Baseline, Week 24
Change From Baseline In UFS-QoL Score by Health-Related Quality of Life Total Score
Time frame: Baseline, Week 24
Number Of Responders With At Least 20 Points Increase From Baseline At Week 24 In UFS-QoL Revised Activities Scale Score
Time frame: From Baseline through Week 24
Change From Baseline in UFS-QoL Bleeding and Pelvic Discomfort Scale Score
Time frame: Baseline, Week 24
Number Of Responders With At Least 20 Points Decrease in UFS-QoL Bleeding And Pelvic Discomfort Scale Score
Time frame: Baseline, Week 24
Change From Baseline At Week 24 In The Interference Of Uterine Fibroids With Physical Activities Based On UFS-QoL Question 11
Time frame: Baseline, Week 24
Change From Baseline At Week 24 In The Interference Of Uterine Fibroids With Social Activities Based On UFS-QoL Question 20
Time frame: Baseline, Week 24
Change From Baseline At Week 24 In Embarrassment Caused By Uterine Fibroids Based On UFS-QoL Question 29
Time frame: Baseline, Week 24
Change From Baseline At Week 24 In Symptoms Assessed Using The Patient Global Assessment (PGA) Questionnaire
Time frame: Baseline, Week 24
Change From Baseline At Week 24 In Function Assessed Using The PGA Questionnaire
Time frame: Baseline, Week 24
Participants Achieving Improvement From Baseline In PGA Questionnaire For Symptoms From Baseline At Week 24
Time frame: From Baseline through Week 24
Participants Achieving Improvement From Baseline In PGA For Uterine Fibroid-related Function From Baseline At Week 24
Time frame: From Baseline through Week 24
Change From Baseline At Week 24 In The Menorrhagia Impact Questionnaire Score For Physical Activities
Time frame: Baseline, Week 24
Change From Baseline At Week 24 In The Menorrhagia Impact Questionnaire Score For Social Activities
Time frame: Baseline, Week 24
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
Time frame: From Baseline up to the last 35 days of treatment (up to 24 weeks)
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
Time frame: Baseline, Week 24
Change From Baseline In Luteinizing Serum Concentration At Week 24
Time frame: Baseline, Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40320117Catherino 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.
- Derived from this study: PubMed 39466126Stewart 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.
- Derived from this study: PubMed 37863160Stewart 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.
- Derived from this study: PubMed 37477173Al-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.
- Derived from this study: PubMed 37183454Al-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.
- Derived from this study: PubMed 36357960Al-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.
- Derived from this study: PubMed 35675604Stewart 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.
- Derived from this study: PubMed 35415708Hunsche 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.
- Derived from this study: PubMed 33596357Al-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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Myovant Medical Monitor study director
Myovant Sciences
127 sites in 8 countries: see every site and its status.
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 127 sites in 8 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 20 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 127 sites in United States, Hungary, Poland, Czechia, Belgium and 3 more countries. 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 20 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 the 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 NCT03103087, which also lists 9 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 20 Apr 2022.