A Placebo-Controlled, Phase 3 Study of Relugolix (TAK-385) 40 mg in the Treatment of Pain Symptoms Associated With Uterine Fibroids

The purpose of this study is to evaluate the efficacy and safety of Relugolix (TAK-385) in patients having pain symptoms associated with uterine fibroids.

The drug being tested in this study is called relugolix (TAK-385). Relugolix is being tested to treat people who have uterine fibroids.

The study enrolled 65 patients. Participants received relugolix placebo in run in period for 3 to 6 weeks. After run-in period, participants were randomly assigned to one of the two treatment groups in 1:1 ratio:

1. Relugolix 40 mg
2. Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient

All participants were asked to take one tablet at the same time each day throughout the study.

This multi-center trial was conducted in Japan. The overall time to participate in this study was 20 to 28 weeks, including run-in period of 3 to 6 weeks and a treatment period of 12 weeks. Participants made multiple visits to the clinic, and 4 weeks after last dose of study drug for a follow-up assessment.

Eligibility Criteria:
Inclusion Criteria:

Inclusion Criteria for Entering the Screening Period (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 a 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 a 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 Period (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 for 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 Period (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 in Inclusion criterion #6).
11. The participant has a maximum Numerical Rating Scale (NRS) score of ≥4 during 1 menstrual cycle just before VISIT 3.
12. The participant has pain symptoms associated with uterine fibroids for at least 2 days during 1 menstrual cycle just before VISIT 3.
13. 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 #13).

Exclusion Criteria:

1. The participant has received any investigational compound within 24 weeks prior to the start of the administration of the study drug for the day of first menstruation after VISIT 1.
2. The participant has received relugolix (including placebo) in a previous clinical study.
3. The participant is an immediate family member or 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, or sibling) or may consent under duress.
4. The participant has lower abdominal pain due to irritable bowel syndrome or severe interstitial cystitis.
5. 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.
6. The participant has a previous or current history of pelvic inflammatory disease within 8 weeks prior to VISIT 1.
7. 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).
8. The participant has a history of panhysterectomy or bilateral oophorectomy.
9. The participant has had markedly abnormal uterine bleeding or anovulatory bleeding, as determined by the investigator or subinvestigator.
10. The participant has a malignant tumor or a history of a malignant tumor within 5 years prior to VISIT 1.
11. The participant has been treated with selective estrogen receptor modulators (SERMs) (excluding drugs for external use and dietary supplements) within 4 weeks prior to VISIT 2.
12. 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).
13. The participant has a previous or current history of severe hypersensitivity or severe allergies to drugs.
14. The participant has nondiagnosable abnormal genital bleeding.
15. 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.
16. 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 Period).
17. The participant is ineligible for this study based on standard 12-lead electrocardiogram (ECG) findings, as determined by the investigator or subinvestigator.
18. 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 VISIT 1 and 2.
19. The participant has a previous or current history of diseases considered to be ineligible for 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, mental disorder (especially depression-like symptoms) and suicide attempt resulting from a mental disorder.
20. The participant has a previous or current history of drug abuse (defined as any illicit drug use) or alcohol abuse.
21. The participant is ineligible for this study for other reasons, as determined by the investigator or subinvestigator.