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Trial record 2 of 3 for:    Relugolix LIBERTY

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

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ClinicalTrials.gov Identifier: NCT03103087
Recruitment Status : Active, not recruiting
First Posted : April 6, 2017
Last Update Posted : November 20, 2018
Sponsor:
Information provided by (Responsible Party):
Myovant Sciences GmbH

Brief Summary:
The purpose of this study is to determine the benefit and safety 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. Additionally, this study is designed to evaluate 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 in the same population.

Condition or disease Intervention/treatment Phase
Heavy Menstrual Bleeding Uterine Fibroid Drug: Relugolix Drug: Estradiol/norethindrone acetate Drug: Placebo for relugolix Drug: Placebo for E2/NETA Phase 3

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 estradiol and norethindrone acetate (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 estradiol and norethindrone acetate (Group B) compared with 24 weeks of placebo (Group C).

Approximately 390 women with heavy menstrual bleeding associated with uterine fibroids will be enrolled in the study and will participate for approximately 10 months. Participation will include an ~ 11 week screening period, 24 weeks of treatment and a follow up period of ~ 30 days. A diagnosis of uterine fibroids will be confirmed during the screening period by centrally-reviewed transvaginal and/or transabdominal ultrasound.

Following successful completion of the Screening period study participants will be randomized to Treatment Group A, B, or C and will attend visits monthly (ie, every 4 weeks). 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.

All patients completing the Week 24 visit, including women randomized to placebo, will be offered the opportunity to enroll in an open-label extension study in which all eligible patients will receive relugolix co-administered with low-dose estradiol and norethindrone acetate. Patients who do not enroll into the extension study will have a follow-up visit approximately 30 days after the end of treatment (ie, after the patient's last dose of study medication).


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 390 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: LIBERTY 2: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Efficacy & Safety Study of Relugolix Co-Administered With/Without Estradiol and Norethindrone Acetate in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids
Actual Study Start Date : March 28, 2017
Estimated Primary Completion Date : September 30, 2019
Estimated Study Completion Date : February 28, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Relugolix plus E2/NETA (Group A)
Relugolix 40 mg co-administered with estradiol (1.0 mg) and norethindrone acetate (0.5 mg) for 24 weeks.
Drug: Relugolix
Relugolix 40 mg tablet administered orally once daily
Other Name: TAK-385

Drug: Estradiol/norethindrone acetate
Capsule containing a co-formulated tablet of estradiol 1.0 mg and norethindrone acetate 0.5 mg administered orally once daily
Other Name: E2/NETA, low-dose hormonal add-back

Experimental: Relugolix -> relugolix+E2/NETA (Group B)
Relugolix 40 mg co-administered with placebo for E2/NETA for 12 weeks followed by relugolix 40 mg co-administered with estradiol/norethindrone acetate (1.0/0.5 mg) for 12 weeks.
Drug: Relugolix
Relugolix 40 mg tablet administered orally once daily
Other Name: TAK-385

Drug: Estradiol/norethindrone acetate
Capsule containing a co-formulated tablet of estradiol 1.0 mg and norethindrone acetate 0.5 mg administered orally once daily
Other Name: E2/NETA, low-dose hormonal add-back

Drug: Placebo for E2/NETA
Placebo capsule administered orally once daily and designed to match the capsule containing E2/NETA in size, shape, color, and odor

Placebo Comparator: Placebo (Group C)
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Drug: Placebo for relugolix
Placebo tablet administered orally once daily and manufactured to match the relugolix tablet in size, shape, color, and odor

Drug: Placebo for E2/NETA
Placebo capsule administered orally once daily and designed to match the capsule containing E2/NETA in size, shape, color, and odor




Primary Outcome Measures :
  1. Responder rate based on reduction in menstrual blood loss (MBL) volume [ Time Frame: from Baseline up to last 35 days of treatment, anticipated to be up to 24 weeks ]
    Defined as the proportion of women who achieve a MBL volume of < 80 mL and a ≥ 50% reduction from Baseline MBL volume over the last 35 days of treatment. MBL volume is measured using the alkaline hematin method. For the primary analysis relugolix Group A will be compared with the placebo Group C.


Secondary Outcome Measures :
  1. Responder rate based on reduction in MBL volume [ Time Frame: from Baseline up to last 35 days of treatment, anticipated to be up to 24 weeks ]
    Defined as the proportion of women who achieve a MBL volume of < 80 mL and a ≥ 50% reduction from Baseline MBL volume over the last 35 days of treatment. MBL volume is measured using the alkaline hematin method. For the secondary analysis relugolix Group B will be compared with the placebo Group C.

  2. Time to MBL response [ Time Frame: up to 24 weeks ]
    Defined as the time to achieve a MBL volume of < 80 mL and a ≥ 50% reduction from Baseline MBL volume as measured by the alkaline hematin method.

  3. Change in MBL volume [ Time Frame: from Baseline up to Week 24 ]
    MBL volume is measured using the alkaline hematin method.

  4. Proportion of women with suppression of bleeding [ Time Frame: from Baseline up to last 35 days of treatment, anticipated to be up to 24 weeks ]
    Will be assessed using patient daily diary and MBL volume measured using the alkaline hematin method.

  5. Change in hemoglobin concentration [ Time Frame: from Baseline up to Week 24 ]
    Blood samples will be collected from participants for hemoglobin measurements.

  6. Change in uterine volume [ Time Frame: from Baseline up to Week 24 ]
    Volume of the uterus will be measured by transvaginal or transabdominal ultrasound.

  7. Change in primary fibroid volume [ Time Frame: from Baseline up to Week 24 ]
    Volume of the primary fibroid will be measured by transvaginal or transabdominal ultrasound.

  8. Change in pain scores in women with pain associated with uterine fibroids at baseline [ Time Frame: from Baseline up to Week 24 ]
    Pain will be assessed with daily diary using a Numerical Rating Scale score (11-point scale) for uterine fibroid-associated pain.

  9. Change in impact on quality of life [ Time Frame: from Baseline up to Week 24 ]
    Assessed using the Uterine Fibroid Symptom Health-Related Quality of Life Questionnaire (UFS-QOL).

  10. Change in Patient Global Assessment (PGA) for symptoms [ Time Frame: from Baseline up to Week 24 ]
    The PGA for symptoms is a 1-item questionnaire designed to assess participants impression of the severity of their symptoms related to uterine fibroids.

  11. Change in PGA for function [ Time Frame: from Baseline up to Week 24 ]
    The PGA for function is a 1-item questionnaire designed to assess participants impression of how their symptoms related to uterine fibroids affected their usual activities.

  12. Bone Mineral Density (BMD) [ Time Frame: from Baseline up to Week 24 ]
    Assessed by dual-energy X-ray absorptiometry (DXA) scan.

  13. The number and percentage of participants with adverse events (AE) as a measure of safety and tolerability [ Time Frame: up to 24 weeks ]
    Assessed by frequency and severity of AEs and serious AEs.

  14. Pharmacokinetics of relugolix, estradiol and norethindrone acetate [ Time Frame: up to 24 weeks ]
    Blood samples will be collected from participants for measurement of relugolix, estradiol and norethindrone concentrations.

  15. Serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH) estradiol (E2) and progesterone (P) [ Time Frame: up to 24 weeks ]
    Blood samples will be collected from participants for hormonal measurements.



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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Is a premenopausal female aged 18 to 50 years old on the day of signing and dating the informed consent form;
  2. Has regularly-occurring menstrual periods of ≤ 14 days duration with a cycle of 21 to 38 days from the start of one menstrual period until the start of the next, by patient history for at least 3 months prior to the Screening 1 visit;
  3. Has a diagnosis of uterine fibroids that is confirmed by a transvaginal and/or transabdominal ultrasound performed with saline or gel contrast during the screening period;
  4. Has heavy menstrual bleeding associated with uterine fibroids as evidenced by a menstrual blood loss of ≥ 80 mL per cycle as measured by the alkaline hematin method during the screening period.

Exclusion Criteria:

  1. Has unexplained vaginal bleeding outside of the patient's regular menstrual cycle;
  2. Has a weight that exceeds the weight limit of the DXA scanner;
  3. 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;
  4. 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;
  5. Has been a participant in an investigational drug or device study within the 1 month prior to Screening.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03103087


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Sponsors and Collaborators
Myovant Sciences GmbH
Investigators
Study Director: Myovant Medical Monitor Myovant Sciences

Responsible Party: Myovant Sciences GmbH
ClinicalTrials.gov Identifier: NCT03103087     History of Changes
Other Study ID Numbers: MVT-601-3002
2016-005113-50 ( EudraCT Number )
First Posted: April 6, 2017    Key Record Dates
Last Update Posted: November 20, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Hemorrhage
Leiomyoma
Myofibroma
Menorrhagia
Pathologic Processes
Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Connective Tissue
Connective Tissue Diseases
Uterine Hemorrhage
Uterine Diseases
Genital Diseases, Female
Menstruation Disturbances
Estradiol
Polyestradiol phosphate
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Estradiol valerate
Norethindrone
Norethindrone acetate
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female
Contraceptives, Oral, Synthetic