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

Inclusion Criteria: Inclusion Criteria for Entering the Screening (at VISIT 1)

1. In the opinion of the investigator or subinvestigator, the participant is capable ofunderstanding and complying with protocol requirements.

2. The participant signs and dates a written, informed consent form prior to theinitiation of any study procedures.

3. Prior to VISIT 1, the participant has a diagnosis of uterine fibroids confirmed bytransvaginal ultrasound, abdominal ultrasound, magnetic resonance imaging (MRI),computed tomography (CT), or laparoscopy, and has never received any surgicaltreatment 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 theinformed consent form.

6. The participant has 1 or more measurable noncalcified myomas with the longest diameterof ≥ 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 3consecutive days.

8. The participant who is sexually active with a nonsterilized male partner agrees to useroutinely adequate contraception from signing of informed consent throughout thestudy. Inclusion Criteria for Entering the Run-in (at VISIT 2)

9. The participant has experienced regular menstrual cycles (25 to 38 days) immediatelyprior 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 diameterof ≥ 3 cm confirmed by transvaginal ultrasound (the same myoma should be measured asin Inclusion criterion #6).

11. The participant has a diagnosis of menorrhagia with a total Pictorial Blood lossAssessment 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 1that should include menstrual bleeding for at least 3 consecutive days (at least 3regular 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 thestart of the administration of the study medication for the Run-in (VISIT 2).

2. The participant has received relugolix (including placebo) in a previous clinicalstudy.

3. The participant is an immediate family member, study site employee, or is in adependent relationship with a study site employee who is involved in conduct of thisstudy (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 tosanitary goods.

6. The participant has lower abdominal pain due to irritable bowel syndrome or severeinterstitial cystitis.

7. The participant has a current history of thyroid gland disorder with irregularmenstruation, or has a potential for irregular menstruation due to thyroid glanddisorder, as determined by the investigator or subinvestigator.

8. The participant has a previous or current history of pelvic inflammatory diseasewithin 8 weeks prior to VISIT 1.

9. The participant has a positive Pap smear test result obtained within 1 year prior toVISIT 1 (if there are no previous test results, those who were judged positive in thetest 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, asdetermined by the investigator or subinvestigator.

12. The participant has a malignant tumor or a history of a malignant tumor within 5 yearsprior to VISIT 1.

13. The participant has been treated with any of the following drugs (excluding drugs forexternal use and dietary supplements) within 4 weeks prior to VISIT 2: anti-coagulantdrugs, 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 priorto VISIT 2: oral contraceptive or sex hormone preparations (norethindrone,norethisterone, medroxyprogesterone, estrogen, or other progestins), and within 16weeks 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 weeksprior to VISIT 2.

16. The participant has a previous or current history of hypersensitivity or allergies toleuprorelin, synthetic GnRH, GnRH agonists or GnRH antagonists, or has a previous orcurrent 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 todonate ova prior to the signing of informed consent, during the study period, orwithin 1 month after the end of the study.

19. The participant has a previous or current history of osteoporosis, osteopenia, orother metabolic bone diseases.

20. The participant has clinically significant cardiovascular disease (eg, myocardialinfarction or unstable angina pectoris within 24 weeks prior to VISIT 1) oruncontrollable hypertension (eg, resting systolic blood pressure ≥ 180 mmHg ordiastolic 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 orsubinvestigator.

22. The participant has active liver disease or jaundice, or with alanine aminotransferase (ALT), aspartate aminotransferase (AST), or bilirubin (total bilirubin) > 1.5 timesthe 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 beinappropriate 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-likesymptoms) or suicide attempt resulting from a mental disorder.

24. The participant has a previous or current history of drug abuse (defined as anyillicit drug use) or alcohol abuse.

25. The participant is inappropriate for participation in this study for other reasons, asdetermined by the investigator or subinvestigator.