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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

February 8, 2017
April 6, 2017
November 20, 2018
March 28, 2017
September 30, 2019   (Final data collection date for primary outcome measure)
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.
Menstrual blood loss volume Group A vs Group C [ Time Frame: 24 weeks ]
Proportion of women in the relugolix Group A versus the placebo Group C who achieve a menstrual blood loss volume of < 80 mL and a 50% reduction from baseline.
Complete list of historical versions of study NCT03103087 on ClinicalTrials.gov Archive Site
  • 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.
  • 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.
  • Change in MBL volume [ Time Frame: from Baseline up to Week 24 ]
    MBL volume is measured using the alkaline hematin method.
  • 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.
  • Change in hemoglobin concentration [ Time Frame: from Baseline up to Week 24 ]
    Blood samples will be collected from participants for hemoglobin measurements.
  • Change in uterine volume [ Time Frame: from Baseline up to Week 24 ]
    Volume of the uterus will be measured by transvaginal or transabdominal ultrasound.
  • 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.
  • 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.
  • 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).
  • 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.
  • 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.
  • Bone Mineral Density (BMD) [ Time Frame: from Baseline up to Week 24 ]
    Assessed by dual-energy X-ray absorptiometry (DXA) scan.
  • 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.
  • 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.
  • 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.
Menstrual blood loss volume Group B vs Group C [ Time Frame: 24 weeks ]
Proportion of women in the relugolix Group B versus the placebo Group C who achieve a menstrual blood loss volume of < 80 mL and a 50% reduction from baseline.
Not Provided
Not Provided
 
LIBERTY 2: Efficacy & Safety Study of Relugolix in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids
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
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.

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).

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
  • Heavy Menstrual Bleeding
  • Uterine Fibroid
  • 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 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
  • 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.
    Interventions:
    • Drug: Relugolix
    • Drug: Estradiol/norethindrone acetate
  • 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.
    Interventions:
    • Drug: Relugolix
    • Drug: Estradiol/norethindrone acetate
    • Drug: Placebo for E2/NETA
  • Placebo Comparator: Placebo (Group C)
    Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
    Interventions:
    • Drug: Placebo for relugolix
    • Drug: Placebo for E2/NETA
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
390
Same as current
February 28, 2020
September 30, 2019   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: Female
18 Years to 50 Years   (Adult)
No
Contact information is only displayed when the study is recruiting subjects
Belgium,   Brazil,   Chile,   Hungary,   Poland,   South Africa,   United States
 
 
NCT03103087
MVT-601-3002
2016-005113-50 ( EudraCT Number )
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: No
Myovant Sciences GmbH
Myovant Sciences GmbH
Not Provided
Study Director: Myovant Medical Monitor Myovant Sciences
Myovant Sciences GmbH
November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP