Study of Relugolix With Estradiol and Norethindrone Acetate in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids
Condition: Uterine Leiomyoma; Uterine Fibroids
MeSH terms: Leiomyoma; Myofibroma; Menorrhagia; Hemorrhage
Study type: Interventional
Phase: Phase 3

Summary: 
      The objectives of this randomized withdrawal study are to evaluate the long-term efficacy and
      safety of the combination of relugolix, estradiol (E2) and norethindrone acetate (NETA), once
      daily, for up to 104 weeks in patients with uterine fibroids who have completed a total of 52
      weeks of treatment, including a 24-week treatment period in a parent study (study
      MVT-601-3001 or MVT-601-3002) and a 28-week treatment period in the open-label extension
      study (MVT-601-3003), and who meet the definition of responder, defined as a patient who
      demonstrates a menstrual blood loss of < 80 mL and at least a 50% reduction from parent study
      baseline menstrual blood loss volume on the alkaline hematin analysis of the feminine
      products returned at Week 48 in the extension study.
    

Detailed description: 
      This randomized withdrawal study is an international phase 3 double-blind, placebo-controlled
      study that will enroll eligible patients with uterine fibroids who have completed the 24-week
      treatment period in a parent study (MVT-601-3001 or MVT-601-3002) and the 28-week treatment
      period of the open-label extension study (MVT-601-3003). When including treatment during the
      parent study and the extension study, patients completing this randomized withdrawal study
      will have received up to a total of 104 weeks of treatment with relugolix.

      Approximately 360 women with heavy menstrual bleeding associated with uterine fibroids
      completing the extension study with a response to treatment will be eligible to participate
      in this study. A responder is defined as a patient who demonstrates a menstrual blood loss of
      < 80 mL and at least a 50% reduction from parent study baseline menstrual blood loss volume
      on the alkaline hematin analysis of the feminine products returned at Week 48 in the
      extension study.

      Screening procedures will be done on the same day as the Week 52 visit for the extension
      study. This visit will be referred to as the "Week 52/Baseline visit." When the Week
      52/Baseline procedures in the extension study have been completed, the investigator will
      assess patient eligibility for participation in this study. The eligibility assessment will
      be based on data available at the Week 52/Baseline visit.

      Patients will be asked to provide feminine products for alkaline hematin analysis at each
      visit until the analysis confirms the return of heavy menstrual bleeding. The patients will
      then be offered retreatment with open-label relugolix with E2/NETA with the onset of the next
      menses. They will resume collection of feminine products for alkaline hematin analysis until
      two consecutive analyses confirm resolution of heavy menstrual bleeding (menstrual blood loss
      of < 80 mL). Safety will be assessed throughout the study by monitoring adverse events, vital
      signs, physical examinations, clinical laboratory tests, and assessments of bone mineral
      density.
    

Intervention name(s): Relugolix; Estradiol/norethindrone acetate; Placebo for relugolix; Placebo for E2/NETA
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Relugolix 40 mg tablet administered orally once daily; Capsule containing co-formulated tablet of estradiol 1.0 mg and norethindrone acetate 0.5 mg administered orally once daily; Placebo tablet administered orally once daily and manufactured to match the relugolix tablet in size, shape, color, and odor; Placebo capsule administered orally once daily and designed to match the E2/NETA capsule in size, shape, color, and odor
Other intervention name(s): TAK-385; E2/NETA; Low-dose hormonal add-back
Intervention MeSH terms: Norethindrone; Norethindrone Acetate; Estradiol; Relugolix
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized withdrawal following an open-label extension to a randomized controlled parent study
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Heavy menstrual bleeding; Menorrhagia; Uterine Fibroids; Uterine Leiomyoma