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

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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.

Official Title
-----------------
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

Conditions
-----------------
Endometriosis

Intervention / Treatment
-----------------
* Drug: Placebo
* Drug: TAK-385
* Drug: TAK-385
* Drug: TAK-385
* Drug: Leuprorelin acetate


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Premenopausal women The participants must have dysmenorrhea and pelvic pain associated with endometriosis. The participant has experienced a regular menstrual cycle. 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: Participants diagnosed with measurable uterine fibroids with the longest diameter of 3 cm or larger Participants with lower abdominal pain due to irritable bowel syndrome or severe interstitial cystitis Participants with a previous or current history of thyroid dysfunction Participants with current or previous history of pelvic inflammatory disease Participants with positive PAP smear test result conducted Participants with a history of panhysterectomy or bilateral oophorectomy Participants judged by investigator to have marked abnormal uterine bleeding or anovulatory bleeding Participants with a previous or current history of a malignant tumor 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 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 Participants who have been treated with bisphosphonate preparation 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 Participants with non-diagnosable abnormal genital bleeding Participants with a previous or current history of osteoporosis, bone mass loss, or other metabolic bone diseases Participants with clinically significant cardiovascular disease or uncontrollable hypertension Participants judged by investigator to be inappropriate to participate in this study based on the 12-lead electrocardiogram (ECG) findings 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

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* TAK-385 placebo-matching tablets, orally, once daily and Leuprorelin acetate placebo injection, subcutaneously, once every 4 weeks for up to 12 weeks.<br>|
| Experimental: TAK-385 10 mg QD<br> | Drug: TAK-385<br>* TAK-385 10 mg, tablets, orally, once daily and Leuprorelin acetate placebo injection, subcutaneously, once every 4 weeks for up to 12 weeks<br>|
| Experimental: TAK-385 20 mg QD<br> | Drug: TAK-385<br>* TAK-385 20 mg, tablets, orally, once daily and Leuprorelin acetate placebo injection, subcutaneously, once every 4 weeks for up to 12 weeks<br>|
| Experimental: TAK-385 40 mg QD<br> | Drug: TAK-385<br>* TAK-385 40 mg, tablets, orally, once daily and Leuprorelin acetate placebo injection, subcutaneously, once every 4 weeks for up to 12 weeks<br>|
| Other: Leuplin<br> | Drug: Leuprorelin acetate<br>* TAK-385 placebo-matching tablets, orally, once daily and Leuprorelin acetate injection, subcutaneously, once every 4 weeks for up to 12 weeks<br>* Other names: Leuplin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Score for pelvic pain as measured by the Visual Analogue Scale (VAS) | Pelvic pain will be assessed using the VAS as pain evaluation scale. | Week 12 (one menstrual cycle) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VAS Score for Pelvic Pain | Pelvic pain will be assessed using the VAS as pain evaluation scale | Up to Week 12. | 
| VAS Score for Dyspareunia | Dyspareunia will be assessed using the VAS as pain evaluation scale | Up to Week 12. | 
| Bone Mineral Density | Measured by Dual-energy X-ray absorptiometry (DXA) | Up to Week 12. | 
| Treatment-emergent Adverse Events. | Treatment-emergent adverse events are defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through the last visit (Week 16) | Up to Week 16 | 
| Vital Signs | Vital signs will include body temperature, sitting blood pressure and pulse (bpm). | Up to Week 12. | 
| Body Weight |  | Up to Week 12. | 
| Electrocardiograms. |  | Up to Week 12. | 
| Number of Participants with Markedly Abnormal Standard Safety Laboratory Values |  | Up to Week 24 | 
| Serum NTx | NTx is one of the biochemical bone metabolism markers | Up to Week 12. | 
| Serum BAP | BAP is one of the biochemical bone metabolism markers | Up to Week 12. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Drug Therapy