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

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ClinicalTrials.gov Identifier: NCT03049735
Recruitment Status : Active, not recruiting
First Posted : February 10, 2017
Last Update Posted : August 9, 2019
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 E2/NETA Drug: Placebo for relugolix 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).


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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 1: 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 : April 26, 2017
Actual Primary Completion Date : April 25, 2019
Estimated Study Completion Date : December 30, 2019

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 plus E2/NETA (Group B)
Relugolix 40 mg co-administered with placebo for E2/NETA for 12 weeks followed by relugolix 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 E2/NETA
Placebo capsule administered orally once daily and designed to match the capsule containing E2/NETA in size, shape, color, and odor

Drug: Placebo for relugolix
Placebo tablet administered orally once daily and manufactured to match the relugolix tablet in size, shape, color, and odor




Primary Outcome Measures :
  1. Proportion of women who achieve a menstrual blood loss (MBL) volume of < 80 mL and a ≥ 50% reduction from Baseline MBL volume over the last 35 days of treatment [ Time Frame: from Baseline up to last 35 days of treatment anticipated to be up to 24 weeks ]
    MBL volume is measured using the alkaline hematin method. For the primary analysis the relugolix plus E2/NETA group will be compared with the placebo group.


Secondary Outcome Measures :
  1. Proportion of women with amenorrhea (no or negligible bleeding) [ Time Frame: from Baseline up to last 35 days of treatment anticipated to be up to 24 weeks ]
    Will be assessed using MBL volume measured using the alkaline hematin method and patient daily diary data.

  2. Change in bleeding and pelvic discomfort scale score [ Time Frame: from Baseline up to Week 24 ]
    Will be assessed with 3 questions (each with a five point scale ranging from 'Not at all' to 'A very great deal') related to menstrual bleeding and pelvic tightness/pressure.

  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 Baseline hemoglobin ≤ 10.5 g/dL who have an increase in hemoglobin > 2 g/dL [ Time Frame: from Baseline up to Week 24 ]
    Blood samples will be collected from participants for hemoglobin measurements.

  5. Proportion of women with maximum pain score ≥ 4 during the last 35 days before randomization whose maximum pain score decreased to ≤ 1 over the last 35 days of treatment [ Time Frame: from Baseline up to Week 24 ]
    Pain will be assessed with a daily diary using a Numerical Rating Scale score (11-point scale) for uterine fibroid-associated pain.

  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. 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.

  9. Change from baseline in MBL volume by visit [ Time Frame: up to 24 weeks ]
    Assessed by the alkaline hematin method.

  10. Change in impact on quality of life [ Time Frame: from Baseline up to Week 24 ]
    Assessed using the UFS-QoL Questionnaire.

  11. 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.

  12. 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.

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

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

  15. 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.

  16. Change in 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.



Information from the National Library of Medicine

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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 dual-energy X-ray absorptiometry 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): NCT03049735


  Show 109 Study Locations
Sponsors and Collaborators
Myovant Sciences GmbH
Investigators
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Study Director: Myovant Medical Monitor Myovant Sciences

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Responsible Party: Myovant Sciences GmbH
ClinicalTrials.gov Identifier: NCT03049735     History of Changes
Other Study ID Numbers: MVT-601-3001
2016-003727-27 ( EudraCT Number )
First Posted: February 10, 2017    Key Record Dates
Last Update Posted: August 9, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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

Additional relevant MeSH terms:
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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
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
Contraceptives, Oral