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

Phase 2

Completed

• Conditions: Endometriosis
• Interventions: Drug: Placebo; Drug: TAK-385; Drug: Leuprorelin acetate

• Registration Number: NCT01458301
• Lead Sponsor: Takeda

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.

Study Timeline

• Study First Submitted: 2011-08-31
• Study Start: 2011-10
• Study First Submitted QC: 2011-10-21
• Study First Posted: 2011-10-24
• Primary Completion: 2013-08
• Study Completion: 2013-08
• Status Verified: 2014-02
• Last Update Submitted: 2014-02-24
• Last Update Posted: 2014-02-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 487

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
TAK-385 10 mg QD	TAK-385	-
TAK-385 20 mg QD	TAK-385	-
TAK-385 40 mg QD	TAK-385	-
Leuplin	Leuprorelin acetate	-

Primary Outcome Measures

Name	Time	Method
Score for pelvic pain as measured by the Visual Analogue Scale (VAS)	Week 12 (one menstrual cycle)	Pelvic pain will be assessed using the VAS as pain evaluation scale.

Secondary Outcome Measures

Name	Time	Method
Serum NTx	Up to Week 12.	NTx is one of the biochemical bone metabolism markers
Serum BAP	Up to Week 12.	BAP is one of the biochemical bone metabolism markers
Vital Signs	Up to Week 12.	Vital signs will include body temperature, sitting blood pressure and pulse (bpm).
Body Weight	Up to Week 12.
Electrocardiograms.	Up to Week 12.
VAS Score for Pelvic Pain	Up to Week 12.	Pelvic pain will be assessed using the VAS as pain evaluation scale
VAS Score for Dyspareunia	Up to Week 12.	Dyspareunia will be assessed using the VAS as pain evaluation scale
Bone Mineral Density	Up to Week 12.	Measured by Dual-energy X-ray absorptiometry (DXA)
Treatment-emergent Adverse Events.	Up to Week 16	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)
Number of Participants with Markedly Abnormal Standard Safety Laboratory Values	Up to Week 24