Efficacy and Safety to Evaluate Relugolix with Women With Heavy Menstrual Bleeding Associated with Uterine Fibroids

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

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2016-003727-27-DE

Enrollment

390

Registered

2017-04-11

Start date

2018-01-19

Completion date

Unknown

Last updated

2018-07-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

heavy menstrual bleeding associated with uterine fibroids MedDRA version: 20.0 Level: LLT Classification code 10027331 Term: Menstrual flow altered System Organ Class: 100000023998 MedDRA version: 20.0 Level: LLT Classification code 10046783 Term: Uterine fibroid System Organ Class: 100000021126

Interventions

Product Name: Relugolix Product Code: TAK-385, RVT-601 Pharmaceutical Form: Film-coated tablet INN or Proposed INN: Relugolix, CAS Number: 737789-87-6 Current Sponsor code: MVT-601 Other descriptive

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Has voluntarily signed and dated the informed consent form prior to initiation of any screening or study-specific procedures; 2. Is a premenopausal female aged 18 to 50 years old (inclusive) on the day of signing and dating the informed consent form; 3. Has regularly-occurring menstrual periods of = 14 days duration with a cycle of 21 to 38 days from the start of one menstrual period until the start of the next, by patient history for at least 3 months prior to the Screening 1 visit; 4. Has a diagnosis of uterine fibroids that is confirmed by a transvaginal ultrasound performed during the screening period. At least one uterine fibroid must be verified by a central reader to meet at least one of the following criteria: a. Subserosal, intramural, or =65 years) no F.1.3.1 Number of subjects for this age r

Exclusion criteria

Exclusion criteria: 1.Has transvaginal and/or transabdominal ultrasound during the screening period demonstrating pathology other than uterine fibroids that could be responsible for or contributing to the patient's heavy menstrual bleeding, such as uterine or cervical polyps >2.0 cm, large simple ovarian cyst >4.0 cm, endometrioma(s) >4.0 cm, or any other clinically significant gynecological disorder determined by the investigator to require further evaluation and/or treatment during the study; Note: Saline or gel contrast is not routinely required. Use of such contrast is required only when the endometrium cannot be evaluated or when there are ambiguous and potentially exclusionary findings on the transvaginal or transabdominal ultrasound (e.g., suspected intrauterine masses, equivocal endometrial findings, etc.); 2. Has known rapidly enlarging uterine fibroids in the opinion of the investigator; 3. Has undergone myomectomy, ultrasound-guided laparoscopic radiofrequency ablation, or any other surgical procedure for fibroids, uterine artery embolization, magnetic resonance-guided focused ultrasound for fibroids, as well as endometrial ablation for abnormal uterine bleeding within 6 months prior to the Screening 1 visit; 4. Has a weight that exceeds the weight limit of the DXA scanner; 5. Has a baseline bone mineral density z-score < -2.0 at spine or total hip; 6. 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 patient's bone mineral density is within normal limits; 7. 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; 8. Anticipated use of systemic glucocorticoids at an oral prednisone-equivalent dose of more than 5 mg every other day during the study. Note: topical, inhaled, intranasal, otic, ophthalmic, intraarticular, or intralesional subcutaneous are permitted without restriction; 9. Gastrointestinal disorder affecting absorption or gastrointestinal motility; 10. Has any contraindication to treatment with low-dose estradiol and norethindrone acetate, including: a. Known, suspected, or history of breast cancer; b. Known or suspected estrogen-dependent neoplasia; c. Active deep vein thrombosis or pulmonary embolism, or history of these conditions prior to the Baseline Day 1 visit; d. History of or active arterial thromboembolic disease, including stroke and myocardial infarction; e. Known anaphylactic reaction or angioedema or hypersensitivity to estradiol or norethindrone acetate; f. Known protein C, protein S, or antithrombin deficiency, or other known thrombophilia disorders, including Factor V Leiden; g. Migraine with aura h. History of porphyria; 11. Has jaundice or known current active liver disease from any cause, including hepatitis A (HAV IgM), hepatitis B (HBsAg), or hepatitis C (HCV Ab positive, confirmed by HCV RNA); 12. Has any of the following cervical pathology: high grade cervical neoplasia, atypical glandular cells, atypical endocervical cells, atypical squamous cells favoring high grade. Of note, patients with atypic

Design outcomes

Primary

Measure	Time frame
Main Objective: To determine the benefit of relugolix 40 mg once daily co-administered with low dose estradiol and norethindrone acetate compared with placebo for 24 weeks on heavy menstrual bleeding associated with uterine fibroids.;Secondary Objective: To determine the benefit of relugolix 40 mg once daily for 12 weeks followed by 12 weeks of relugolix 40 mg once daily co-administered with low dose estradiol and norethindrone acetate compared with placebo for 24 weeks on heavy menstrual bleeding associated with uterine fibroids; To determine the benefit of 24 weeks of relugolix 40 mg once daily co-administered with either 12 or 24 weeks of low dose estradiol and norethindrone acetate compared with placebo for 24 weeks on the following: Change in hemoglobin; Impact of heavy menstrual bleeding on social, leisure, and physical activities; Pain associated with uterine fibroids; Uterine volume; and Uterine fibroid volume. To determine the safety of 24 weeks of relugolix 40 mg once daily co-administered with either 12 or 24 weeks of low dose estradiol and norethindrone acetate in women with heavy menstrual bleeding associated with uterine fibroids compared with placebo for 24 weeks; Please see all objectives in the protocol;Primary end point(s): Proportion of women in the relugolix Group A versus the placebo Group C who achieve a menstrual blood loss volume of < 80 mL AND at least a 50% reduction from baseline menstrual blood loss volume, as measured by the alkaline hematin method.;Timepoint(s) of evaluation of this end point: over the last 35 days of 24 weeks of treatment	—

Measure

Time frame

Main Objective: To determine the benefit of relugolix 40 mg once daily co-administered with low dose estradiol and norethindrone acetate compared with placebo for 24 weeks on heavy menstrual bleeding associated with uterine fibroids.;Secondary Objective: To determine the benefit of relugolix 40 mg once daily for 12 weeks followed by 12 weeks of relugolix 40 mg once daily co-administered with low dose estradiol and norethindrone acetate compared with placebo for 24 weeks on heavy menstrual bleeding associated with uterine fibroids; To determine the benefit of 24 weeks of relugolix 40 mg once daily co-administered with either 12 or 24 weeks of low dose estradiol and norethindrone acetate compared with placebo for 24 weeks on the following: Change in hemoglobin; Impact of heavy menstrual bleeding on social, leisure, and physical activities; Pain associated with uterine fibroids; Uterine volume; and Uterine fibroid volume. To determine the safety of 24 weeks of relugolix 40 mg once daily co-administered with either 12 or 24 weeks of low dose estradiol and norethindrone acetate in women with heavy menstrual bleeding associated with uterine fibroids compared with placebo for 24 weeks; Please see all objectives in the protocol;Primary end point(s): Proportion of women in the relugolix Group A versus the placebo Group C who achieve a menstrual blood loss volume of < 80 mL AND at least a 50% reduction from baseline menstrual blood loss volume, as measured by the alkaline hematin method.;Timepoint(s) of evaluation of this end point: over the last 35 days of 24 weeks of treatment

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Secondary

Measure	Time frame
Secondary end point(s): Proportion of women in the relugolix Group B versus the placebo Group C who achieve a menstrual blood loss volume of < 80 mL AND at least a 50% reduction from baseline menstrual blood loss volume , as measured by the alkaline hematin method. The following secondary endpoints will be assessed comparing each relugolix treatment group to placebo inferentially and relugolix Group A to Group B descriptively: Time to achieving a menstrual blood loss volume of < 80 mL AND at least a 50% reduction from baseline menstrual blood loss volume as measured by the alkaline hematin method; Change from Baseline to Week 24 in menstrual blood loss; Proportion of women who achieve amenorrhea as measured by the alkaline hematin method; Time to amenorrhea as measured by the by the alkaline hematin method; Proportion of women with a hemoglobin below the lower limit of normal at Baseline who achieve an increase of = 1 g/dL from Baseline at Week 24; Change from Baseline to Week 24 in the Menorrhagia Impact Questionnaire Score for physical activities; Change from Baseline to Week 24 in the Menorrhagia Impact Questionnaire Score for social and leisure activities; Proportion of women who achieve a mean Numerical Rating Scale score for uterine fibroid-associated pain that is at least a 30% reduction from Baseline in the subset of women with a maximum pain score = 4 during the 35 days prior to randomization; Change from Baseline to Week 24 in uterine volume; and Change from Baseline to Week 24 in uterine fibroid volume. Treatment-emergent adverse events, change in vital signs (including weight), clinical laboratory tests, and electrocardiograms; Percent change from Baseline to Weeks 12 and 24 in bone mineral density at the spine (average of L1-L4), total hip, and femoral neck as assessed by DXA; Incidence of vasomotor symptoms. ;Timepoint(s) of evaluation of this end point: over the last 35 days of 24 weeks of treatment	—

Measure

Time frame

Secondary end point(s): Proportion of women in the relugolix Group B versus the placebo Group C who achieve a menstrual blood loss volume of < 80 mL AND at least a 50% reduction from baseline menstrual blood loss volume , as measured by the alkaline hematin method. The following secondary endpoints will be assessed comparing each relugolix treatment group to placebo inferentially and relugolix Group A to Group B descriptively: Time to achieving a menstrual blood loss volume of < 80 mL AND at least a 50% reduction from baseline menstrual blood loss volume as measured by the alkaline hematin method; Change from Baseline to Week 24 in menstrual blood loss; Proportion of women who achieve amenorrhea as measured by the alkaline hematin method; Time to amenorrhea as measured by the by the alkaline hematin method; Proportion of women with a hemoglobin below the lower limit of normal at Baseline who achieve an increase of = 1 g/dL from Baseline at Week 24; Change from Baseline to Week 24 in the Menorrhagia Impact Questionnaire Score for physical activities; Change from Baseline to Week 24 in the Menorrhagia Impact Questionnaire Score for social and leisure activities; Proportion of women who achieve a mean Numerical Rating Scale score for uterine fibroid-associated pain that is at least a 30% reduction from Baseline in the subset of women with a maximum pain score = 4 during the 35 days prior to randomization; Change from Baseline to Week 24 in uterine volume; and Change from Baseline to Week 24 in uterine fibroid volume. Treatment-emergent adverse events, change in vital signs (including weight), clinical laboratory tests, and electrocardiograms; Percent change from Baseline to Weeks 12 and 24 in bone mineral density at the spine (average of L1-L4), total hip, and femoral neck as assessed by DXA; Incidence of vasomotor symptoms. ;Timepoint(s) of evaluation of this end point: over the last 35 days of 24 weeks of treatment

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Countries

Argentina, Brazil, Germany, Italy, Poland, South Africa, United Kingdom, United States

Contacts

Public ContactMelinda Whiteside

Myovant Sciences GmbH

melinda.whiteside@myovant.com+1650 235 4048

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026