A Phase 3 Study to Evaluate the Efficacy and Safety of Relugolix (TAK-385) 40 mg Compared With Leuprorelin in the Treatment of Uterine Fibroids
Condition: Uterine Fibroids
MeSH terms: Leiomyoma; Myofibroma
Intervention: Relugolix; Relugolix Placebo; Leuprorelin; Leuprorelin Placebo
Intervention description: Relugolix tablets; Relugolix placebo-matching tablets; Leuprorelin injection; Leuprorelin placebo-matching injections
Intervention MeSH terms: Leuprolide; Relugolix
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 281.0
Sex: Female
Minimum age: 20 Years
Healthy volunteers: No
Keywords: Drug Therapy

Summary:

      The purpose of this study is to evaluate the efficacy of Relugolix (TAK-385) 40 mg
      administered orally once daily for 12 weeks, compared with leuprorelin injection (once every
      4 weeks, 1.88 mg or 3.75 mg subcutaneously [SC]/time) in patients with uterine fibroids.
    

Eligibility criteria:

        Inclusion Criteria:

        Inclusion Criteria for Entering the Screening (at VISIT 1)

          1. In the opinion of the investigator or subinvestigator, the participant is capable of
             understanding and complying with protocol requirements.

          2. The participant signs and dates a written, informed consent form prior to the
             initiation of any study procedures.

          3. Prior to VISIT 1, the participant has a diagnosis of uterine fibroids confirmed by
             transvaginal ultrasound, abdominal ultrasound, magnetic resonance imaging (MRI),
             computed tomography (CT), or laparoscopy, and has never received any surgical
             treatment for the myoma (measurable noncalcified myoma with the longest diameter of ≥
             3 cm).

          4. The participant is a premenopausal Japanese woman.

          5. The participant is aged 20 years or older on the day of signing and dating the
             informed consent form.

          6. The participant has 1 or more measurable noncalcified myomas with the longest diameter
             of ≥ 3 cm confirmed by transvaginal ultrasound.

          7. The participant has experienced 1 or more regular menstrual cycles (25 to 38 days)
             immediately prior to VISIT 1 and that should include menstrual bleeding for at least 3
             consecutive days.

          8. The participant who is sexually active with a nonsterilized male partner agrees to use
             routinely adequate contraception from signing of informed consent throughout the
             study.

             Inclusion Criteria for Entering the Run-in (at VISIT 2)

          9. The participant has experienced regular menstrual cycles (25 to 38 days) immediately
             prior to VISIT 2 that should include menstrual bleeding of at least 3 consecutive days
             (at least 2 regular menstruation cycles to be confirmed by Inclusion criteria #7 and
             #9).

             Inclusion Criteria for Entering the Treatment (at VISIT 3)

         10. The participant has 1 or more measurable noncalcified myomas, with a longest diameter
             of ≥ 3 cm confirmed by transvaginal ultrasound (the same myoma should be measured as
             in Inclusion criterion #6).

         11. The participant has a diagnosis of menorrhagia with a total Pictorial Blood loss
             Assessment Chart (PBAC) score of ≥ 120 in 1 menstrual cycle just before VISIT 3.

         12. The participant has experienced regular menstrual cycles (25 to 38 days) after VISIT 1
             that should include menstrual bleeding for at least 3 consecutive days (at least 3
             regular menstruation cycles to be confirmed by Inclusion criteria #7, #9 and #12).

        Exclusion Criteria:

          1. The participant has received any investigational compound within 24 weeks prior to the
             start of the administration of the study medication for the Run-in (VISIT 2).

          2. The participant has received relugolix (including placebo) in a previous clinical
             study.

          3. The participant is an immediate family member, study site employee, or is in a
             dependent relationship with a study site employee who is involved in conduct of this
             study (eg, spouse, parent, child, sibling) or may consent under duress.

          4. The participant has a previous or current history of blood disorders (eg, thalassemia,
             sickle cells anemia, folic-acid deficiency, and coagulopathy), excluding (latent)
             iron-deficiency anemia.

          5. The participant has a known history of severe hypersensitivity or severe allergy to
             sanitary goods.

          6. The participant has lower abdominal pain due to irritable bowel syndrome or severe
             interstitial cystitis.

          7. The participant has a current history of thyroid gland disorder with irregular
             menstruation, or has a potential for irregular menstruation due to thyroid gland
             disorder, as determined by the investigator or subinvestigator.

          8. The participant has a previous or current history of pelvic inflammatory disease
             within 8 weeks prior to VISIT 1.

          9. The participant has a positive Pap smear test result obtained within 1 year prior to
             VISIT 1 (if there are no previous test results, those who were judged positive in the
             test conducted before VISIT 2).

         10. The participant has a history of panhysterectomy or bilateral oophorectomy.

         11. The participant has had markedly abnormal uterine bleeding or anovulatory bleeding, as
             determined by the investigator or subinvestigator.

         12. The participant has a malignant tumor or a history of a malignant tumor within 5 years
             prior to VISIT 1.

         13. The participant has been treated with any of the following drugs (excluding drugs for
             external use and dietary supplements) within 4 weeks prior to VISIT 2: anti-coagulant
             drugs, anti-platelet drugs, tranexamic acid, selective estrogen receptor modulators
             (SERMs), activated vitamin D preparations, other vitamin D preparations, calcitonin,
             ipriflavone, steroid hormones, vitamin K preparations, teriparatide, or denosumab.

         14. The participant has been treated with any of the following drugs within 8 weeks prior
             to VISIT 2: oral contraceptive or sex hormone preparations (norethindrone,
             norethisterone, medroxyprogesterone, estrogen, or other progestins), and within 16
             weeks prior to VISIT 2: gonadotropin-releasing hormone (GnRH) analogues, dienogest,
             danazol, or aromatase inhibitors (for 1- and 3-month sustained-release preparations,
             within 20 and 28 weeks prior to VISIT 2, respectively).

         15. The participant has been treated with a bisphosphonate preparation within 24 weeks
             prior to VISIT 2.

         16. The participant has a previous or current history of hypersensitivity or allergies to
             leuprorelin, synthetic GnRH, GnRH agonists or GnRH antagonists, or has a previous or
             current history of severe hypersensitivity or severe allergy to other drugs.

         17. The participant has nondiagnosable abnormal genital bleeding.

         18. Female participant who is pregnant, lactating, or intending to become pregnant or to
             donate ova prior to the signing of informed consent, during the study period, or
             within 1 month after the end of the study.

         19. The participant has a previous or current history of osteoporosis, osteopenia, or
             other metabolic bone diseases.

         20. The participant has clinically significant cardiovascular disease (eg, myocardial
             infarction or unstable angina pectoris within 24 weeks prior to VISIT 1) or
             uncontrollable hypertension (eg, resting systolic blood pressure ≥ 180 mmHg or
             diastolic blood pressure ≥ 110 mmHg at Screening and Run-in).

         21. The participant is inappropriate for participation in this study based on standard
             12-lead electrocardiogram (ECG) findings, as determined by the investigator or
             subinvestigator.

         22. The participant has active liver disease or jaundice, or with alanine aminotransferase
             (ALT), aspartate aminotransferase (AST), or bilirubin (total bilirubin) > 1.5 times
             the upper limit of normal (ULN) in the clinical laboratory tests at VISITs 1 and 2.

         23. The participant has previous or current history of diseases considered to be
             inappropriate for participation in this study, including severe hepatic impairment,
             jaundice, renal impairment, cardiovascular disease, endocrine system disease,
             metabolic disorder, pulmonary disease, gastrointestinal disease, neurological disease,
             urological disease, immune disease, or mental disorder (especially depression-like
             symptoms) or suicide attempt resulting from a mental disorder.

         24. The participant has a previous or current history of drug abuse (defined as any
             illicit drug use) or alcohol abuse.

         25. The participant is inappropriate for participation in this study for other reasons, as
             determined by the investigator or subinvestigator.