Efficacy and Safety of TAK-385 in the Treatment of Uterine Fibroids

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 Uterine Fibroids

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

Study Overview

• Status: Completed
• Conditions: Uterine Fibroids
• Intervention / Treatment: Drug: TAK-385; Drug: TAK-385; Drug: TAK-385; Drug: Placebo

Detailed Description

This study is a Phase II, multicenter, randomized, double-blind, parallel-group, placebo-controlled for evaluation of the efficacy and safety of TAK-385 10, 20, and 40 mg (p.o.) following once daily administration for 12 weeks in women with uterine fibroids.

• Study Type: Interventional
• Enrollment (Actual): 216
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Chiba
    • Chiba-shi, Chiba, Japan
    • Itchihara-shi, Chiba, Japan
    • Matsuno-shi, Chiba, Japan
  • Ehime
    • Matsuyama-shi, Ehime, Japan
    • Nihama-shi, Ehime, Japan
  • Fukui
    • Fukui-shi, Fukui, Japan
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan
    • Iizuka-shi, Fukuoka, Japan
    • Yanagigawa-shi, Fukuoka, Japan
  • Gunma
    • Mebashi-shi, Gunma, Japan
  • Hokkaido
    • Ebetsu-shi, Hokkaido, Japan
    • Sapporo-shi, Hokkaido, Japan
  • Hyogo
    • Amagasaki-shi, Hyogo, Japan
    • Kobe-shi, Hyogo, Japan
  • Kanagawa
    • Kamakura-shi, Kanagawa, Japan
    • Yokohama-shi, Kanagawa, Japan
  • Oita
    • Oita-shi, Oita, Japan
  • Osaka
    • Ibaraki-shi, Osaka, Japan
    • Osaka-shi, Osaka, Japan
    • Sakai-shi, Osaka, Japan
    • Tondabayashi-shi, Osaka, Japan
  • Tokyo
    • Chuo-ku, Tokyo, Japan
    • Itabashi-ku, Tokyo, Japan
    • Setagaya-ku, Tokyo, Japan
    • Shinagawa-ku, Tokyo, Japan
    • Suginami-ku, Tokyo, Japan
  • Toyama
    • Toyama-shi, Toyama, 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. The participant has been diagnosed with uterine fibroids and has never received surgical treatment for the myoma.
2. The participant is a premenopausal woman.
3. The participant has one or more measurable noncalcified myomas confirmed by transvaginal sonography.
4. The participant has experienced regular menstrual cycles
5. The participant is diagnosed as menorrhagia

Exclusion Criteria:

1. Participants with a screening Hb <8 g/dL
2. Participants with a previous or current history of blood disorders
3. Participants with a known history of severe hypersensitivity or severe allergy to sanitary goods
4. Participants with lower abdominal pain due to irritable bowel syndrome or severe interstitial cystitis
5. Participants with a previous or current history of thyroid dysfunction
6. Participants with a previous or current history of pelvic inflammatory disease
7. Participants with a positive PAP smear test result
8. Participants with a history of panhysterectomy or bilateral oophorectomy
9. Participants judged by investigator to have marked abnormal uterine bleeding or anovulatory bleeding
10. Participants with a previous or current history of a malignant tumor
11. 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
12. 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
13. Participants who have been treated with a bisphosphonate preparation
14. Participants with a previous or current history of severe hypersensitivity or severe allergy to drugs
15. Participants with non-diagnosable abnormal genital bleeding
16. Participants with a previous or current history of osteoporosis, bone mass loss, or other metabolic bone diseases
17. Participants with clinically significant cardiovascular disease or uncontrollable hypertension
18. Participants judged by investigator to be inappropriate to participate in this study based on the 12-lead electrocardiogram (ECG) findings
19. 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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; TAK-385 placebo-matching tablets, orally, once daily for up to 12 weeks.
Experimental: TAK-385 10 mg QD	Drug: TAK-385; TAK-385 10 mg, tablets, orally, once daily for up to 12 weeks.; Drug: TAK-385; TAK-385 20 mg, tablets, orally, once daily for up to 12 weeks.; Drug: TAK-385; TAK-385 40 mg, tablets, orally, once daily for up to 12 weeks.
Experimental: TAK-385 20 mg QD	Drug: TAK-385; TAK-385 10 mg, tablets, orally, once daily for up to 12 weeks.; Drug: TAK-385; TAK-385 20 mg, tablets, orally, once daily for up to 12 weeks.; Drug: TAK-385; TAK-385 40 mg, tablets, orally, once daily for up to 12 weeks.
Experimental: TAK-385 40 mg QD	Drug: TAK-385; TAK-385 10 mg, tablets, orally, once daily for up to 12 weeks.; Drug: TAK-385; TAK-385 20 mg, tablets, orally, once daily for up to 12 weeks.; Drug: TAK-385; TAK-385 40 mg, tablets, orally, once daily for up to 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decrease in menstrual blood loss	Blood loss will be assessed using the Pictorial Blood Loss Assessment Chart (PBAC).	Week 12 (one menstrual cycle)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone Mineral Density	Measured by Dual-energy X-ray absorptiometry (DXA)	Up to Week 12.
Body Weight		Up to Week 12.
Decrease in menstrual blood loss	Blood loss will be assessed using PBAC	Up to Week 6
Decrease in menstrual blood loss	Blood loss will be assessed using PBAC	Up to Week 12.
Amenorrhea	Amenorrhea will be assessed using PBAC	Week 12 (one menstrual cycle).
Amenorrhea	Amenorrhea will be assessed using PBAC	Up to Week 6.
Amenorrhea	Amenorrhea will be assessed using PBAC	Up to Week 12.
Change in menstrual blood loss	Change in menstrual blood loss measured by PBAC	Week 12 (one menstrual cycle)
Myoma Volume		Up to Week 12.
Uterine Volume		Up to Week 12.
Hemoglobin Concentration in Blood		Up to Week 12.
Pain Symptom	Measured by Numerical Rating Scale.	Up to Week 12.
Other Clinical Symptoms	Assessed by clinical laboratory tests	Up to Week 12.
Quality of Life (QOL) Score	QOL will be assessed using Uterine Fibroid Symptom and Quality of Life (UFS-QOL)	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.
Electrocardiograms	Up to Week 12.
Laboratory Values		Up to Week 12
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

• Hoshiai H, Seki Y, Kusumoto T, Kudou K, Tanimoto M. Relugolix for oral treatment of uterine leiomyomas: a dose-finding, randomized, controlled trial. BMC Womens Health. 2021 Oct 28;21(1):375. doi: 10.1186/s12905-021-01475-2.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: August 31, 2011
• First Submitted That Met QC Criteria: October 12, 2011
• First Posted (Estimate): October 17, 2011

Study Record Updates

• Last Update Posted (Estimate): January 21, 2013
• Last Update Submitted That Met QC Criteria: January 17, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Connective Tissue Diseases; Neoplasms, Connective Tissue; Neoplasms, Muscle Tissue; Leiomyoma; Myofibroma; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Androgen Antagonists; Relugolix
• Other Study ID Numbers: TAK-385/CCT-001; U1111-1123-6815 (Registry Identifier: WHO); JapicCTI-111590 (Registry Identifier: JapicCTI)