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.

Study Overview

• Status: Completed
• Conditions: Endometriosis
• Intervention / Treatment: Drug: Placebo; Drug: TAK-385; Drug: TAK-385; Drug: TAK-385; Drug: Leuprorelin acetate

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 Type: Interventional
• Enrollment (Actual): 487
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Aichi
    • Nagoya-shi, Aichi, Japan
  • Chiba
    • Chiba-shi, Chiba, Japan
    • Funabashi-shi, Chiba, Japan
    • Ichihara-shi, Chiba, Japan
    • Yachiyo-shi, Chiba, Japan
  • Ehime
    • Nihama-shi, Ehime, Japan
  • Fukui
    • Fukui-shi, Fukui, Japan
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan
    • Iizuka-shi, Fukuoka, Japan
    • Kitakyushu-shi, Fukuoka, Japan
    • Onga-gun, Fukuoka, Japan
    • Yanagawa-shi, Fukuoka, Japan
  • Fukushima
    • Koriyama-shi, Fukushima, Japan
  • Gifu
    • Takayama-shi, Gifu, Japan
  • Gunma
    • Takasaki-shi, Gunma, Japan
  • Hirosima
    • Hirosima-shi, Hirosima, Japan
  • Hokkaido
    • Ebetsu-shi, Hokkaido, Japan
    • Ishikari-shi, Hokkaido, Japan
    • Sapporo-shi, Hokkaido, Japan
  • Hyogo
    • Amagasaki-shi, Hyogo, Japan
    • Kako-gun, Hyogo, Japan
    • Kawanishi-shi, Hyogo, Japan
    • Kobe-shi, Hyogo, Japan
  • Ishikawa
    • Kanazawa-shi, Ishikawa, Japan
  • Kagawa
    • Marugame-shi, Kagawa, Japan
  • Kagoshima
    • Kagoshima-shi, Kagoshima, Japan
  • Kanagawa
    • Hiratsuka-shi, Kanagawa, Japan
    • Kamakura-shi, Kanagawa, Japan
    • Kawasaki-shi, Kanagawa, Japan
    • Yamato-shi, Kanagawa, Japan
    • Yokohama-shi, Kanagawa, Japan
  • Kochi
    • Nankoku-shi, Kochi, Japan
  • Kumamoto
    • Kumamoto-shi, Kumamoto, Japan
  • Kyoto
    • Kyoto-shi, Kyoto, Japan
  • Miyagi
    • Sendai-shi, Miyagi, Japan
  • Nagano
    • Matsumoto-shi, Nagano, Japan
    • Nagano-shi, Nagano, Japan
    • Suzaka-shi, Nagano, Japan
  • Nara
    • Nara-shi, Nara, Japan
  • Oita
    • Oita-shi, Oita, Japan
  • Okayama
    • Kurashiki-shi, Okayama, Japan
    • Okayama-shi, Okayama, Japan
  • Osaka
    • Hirakata-shi, Osaka, Japan
    • Ibaraki-shi, Osaka, Japan
    • Ikeda-shi, Osaka, Japan
    • Osaka-shi, Osaka, Japan
    • Sakai-shi, Osaka, Japan
    • Suita-shi, Osaka, Japan
    • Tondabayashi-shi, Osaka, Japan
    • Toyonaka-shi, Osaka, Japan
  • Saitama
    • Iruma-shi, Saitama, Japan
  • Shiga
    • Kusatsu-shi, Shiga, Japan
  • Shizuoka
    • Hamamatsu-shi, Shizuoka, Japan
    • Numazu-shi, Shizuoka, Japan
    • Yaizu-shi, Shizuoka, Japan
  • Tokushima
    • Komatsushima-shi, Tokushima, Japan
    • Naruto-shi, Tokushima, Japan
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan
    • Chiyoda-ku, Tokyo, Japan
    • Chuo-ku, Tokyo, Japan
    • Itabashi-ku, Tokyo, Japan
    • Machida-shi, Tokyo, Japan
    • Minato-ku, Tokyo, Japan
    • Ohta-ku, Tokyo, Japan
    • Setagaya-ku, Tokyo, Japan
    • Shinagawa-ku, Tokyo, Japan
    • Suginami-ku, Tokyo, Japan
  • Toyama
    • Toyama-shi, Toyama, Japan
  • Yamaguchi
    • Yamaguchi-shi, Yamaguchi, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

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

Collaborators and Investigators

• Sponsor: Takeda

Publications and helpful links

General Publications

• Osuga Y, Seki Y, Tanimoto M, Kusumoto T, Kudou K, Terakawa N. Relugolix, an oral gonadotropin-releasing hormone receptor antagonist, reduces endometriosis-associated pain in a dose-response manner: a randomized, double-blind, placebo-controlled study. Fertil Steril. 2021 Feb;115(2):397-405. doi: 10.1016/j.fertnstert.2020.07.055. Epub 2020 Sep 7.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: August 31, 2011
• First Submitted That Met QC Criteria: October 21, 2011
• First Posted (Estimate): October 24, 2011

Study Record Updates

• Last Update Posted (Estimate): February 25, 2014
• Last Update Submitted That Met QC Criteria: February 24, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Endometriosis; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Androgen Antagonists; Leuprolide; Relugolix
• Other Study ID Numbers: TAK-385/CCT-101; U1111-1123-6890 (Registry Identifier: WHO); JapicCTI-111588 (Registry Identifier: JapicCTI)