Efficacy and Safety of TAK-385 in the Treatment of Endometriosis

A Phase II, Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Study of the Efficacy and Safety of TAK-385 10, 20, and 40 mg (p.o.) in the Treatment of Endometriosis

The purpose of this study is to determine the efficacy and safety of TAK-385, once daily (QD), for 12 weeks in women with endometriosis.

This Phase II, multicenter, double-blind, randomized, parallel-group, placebo-controlled study will evaluate the efficacy and safety of 3 dose levels (10, 20, and 40 mg) of TAK-385 following oral administration for 12 weeks in women with endometriosis.

Inclusion Criteria:

1. Premenopausal women

2. The participants must have dysmenorrhea and pelvic pain associated with endometriosis.

3. The participant has experienced a regular menstrual cycle.

4. The participant has been diagnosed with endometriosis by method a), b), or c).

   • Laparotomy
   • Laparoscopy
   • Chocolate cyst of the ovary confirmed by MRI

Exclusion Criteria:

1. Participants diagnosed with measurable uterine fibroids with the longest diameter of 3 cm or larger
2. Participants with lower abdominal pain due to irritable bowel syndrome or severe interstitial cystitis
3. Participants with a previous or current history of thyroid dysfunction
4. Participants with current or previous history of pelvic inflammatory disease
5. Participants with positive PAP smear test result conducted
6. Participants with a history of panhysterectomy or bilateral oophorectomy
7. Participants judged by investigator to have marked abnormal uterine bleeding or anovulatory bleeding
8. Participants with a previous or current history of a malignant tumor
9. Participants who have been treated with any of the following drugs: anticoagulant drug, antiplatelet drug, tranexamic acid, selective estrogen receptor modulator (SERM), activated vitamin D, other vitamin D, calcitonin, ipriflavone, steroid hormone, vitamin K, teriparatide,or denosumab
10. Participants who have been treated with any of the following drugs: oral contraceptive and sex hormone preparation, gonadotropin-releasing hormone (GnRH) analogue, dienogest, danazol, or aromatase inhibitor
11. Participants who have been treated with bisphosphonate preparation
12. Participants with a previous or current history of hypersensitivity or allergy to Leuplin, synthetic LH-RH, LH-RH derivatives, gelatin-containing formulations or food containing gelatin, or have a previous or current history of severe hypersensitivity or severe allergy to other drugs
13. Participants with non-diagnosable abnormal genital bleeding
14. Participants with a previous or current history of osteoporosis, bone mass loss, or other metabolic bone diseases
15. Participants with clinically significant cardiovascular disease or uncontrollable hypertension
16. Participants judged by investigator to be inappropriate to participate in this study based on the 12-lead electrocardiogram (ECG) findings
17. Participants with active liver disease or jaundice, or with alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin > 1.5 times the upper limit of normal (ULN) in the clinical laboratory tests