Clinical Study to Evaluate Efficacy and Safety of TAK-385 40 mg Compared With Leuprorelin in Patients With Endometriosis

December 10, 2020 updated by: ASKA Pharmaceutical Co., Ltd.

Phase III Clinical Study to Evaluate Efficacy and Safety of TAK-385 40 mg Compared With Leuprorelin in Patients With Endometriosis

The objective is to evaluate the efficacy and safety of TAK-385 40 mg orally administrated once daily for 24 weeks compared with Leuprorelin [once/4 weeks, 3.75 or 1.88 mg subcutaneously (SC)/time] in patients with endometriosis.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This study is a phase III, multicenter, randomized, double-blind, parallel-group study to investigate the efficacy and safety of TAK-385 40 mg once daily compared with leuprorelin (once/4 weeks, 3.75 or 1.88 mg SC/time) in premenopausal subjects ≥ 20 years of age with endometriosis. 320 women with endometriosis will be enrolled in the study. This study consists of screening of approximately 1 to 6 weeks, run-in of approximately 3 to 6 weeks, treatment of 24 weeks, and follow-up of 4 weeks. After signing the informed consent form, subjects should record their symptoms in the electronic patient diary every day. During run-in period, daily data will be collected in the electronic patient diary for calculation of the baseline values for the efficacy evaluation.Following run-in period, subjects will receive investigational products (TAK-385 + leuprorelin placebo or TAK-385 placebo + leuprorelin) under double blind. During this study, subjects will visit the study center to undergo the designated examinations and evaluations at each visit. Safety will be assessed throughout the study by monitoring adverse events, vital signs, physical examinations, clinical laboratory tests, 12-lead electrocardiograms (ECG), and assessments of bone mineral density.Subjects will visit the study center to undergo the designated examinations and evaluations at 28 days after final administration.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
335

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
      • Aichi, Japan
        • Chubu Rosai Hospital
      • Aichi, Japan
        • Meitetsu Hospital
      • Chiba, Japan
        • Chiba Aoba Municipal Hospital
      • Chiba, Japan
        • Aiiku Ladies Clinic
      • Chiba, Japan
        • Tokyo Bay Urayasu Ichikawa Medical Center
      • Chiba, Japan
        • Tsujinaka Hospital Kashiwanoha
      • Hiroshima, Japan
        • Fujito Clinic
      • Hokkaido, Japan
        • Hashimoto Clinic
      • Hokkaido, Japan
        • Tokeidai Memorial Hospital
      • Hokkaido, Japan
        • Yoshio Obstetrics Gynecology Hospital
      • Hyogo, Japan
        • Shinsuma Hospital
      • Kagawa, Japan
        • Kagawa Prefectural Central Hospital
      • Kagawa, Japan
        • Takamatsu Red Cross Hospital
      • Kanagawa, Japan
        • Fujisawa City Hospital
      • Kanagawa, Japan
        • Rinkan Clinic
      • Kanagawa, Japan
        • Second Kawasaki Saiwai Clinic
      • Kanagawa, Japan
        • Tawada Ladies Clinic
      • Kumamoto, Japan
        • Japanese Red Cross Kumamoto Hospital
      • Okayama, Japan
        • Kurashiki Medical Clinic
      • Osaka, Japan
        • Chayamachi Ladies Clinic
      • Osaka, Japan
        • Hayakawa Clinic
      • Osaka, Japan
        • Minami-Morimachi Ladies Clinic
      • Osaka, Japan
        • Nomura Clinic Nanba
      • Osaka, Japan
        • Rikako Ladies Clinic
      • Osaka, Japan
        • Tanabe Ladies Clinic
      • Osaka, Japan
        • Yoshimura Ladies Clinic
      • Saitama, Japan
        • Dantsuka Clinic
      • Saitama, Japan
        • Kashiwazaki ladies clinic
      • Saitama, Japan
        • Maruyama Memorial General Hospital
      • Shiga, Japan
        • Kusatsu General Hospital
      • Tokyo, Japan
        • Akasaka-Mitsuke Miyazaki Clinic
      • Tokyo, Japan
        • Ginza Yoshida Hospital
      • Tokyo, Japan
        • Hamada Hospital
      • Tokyo, Japan
        • Ikebukuro Metroporitan Clinic
      • Tokyo, Japan
        • NS Clinic
      • Tokyo, Japan
        • Sei Women's Clinic
      • Tokyo, Japan
        • Seijo Kinoshita Hospital
      • Tokyo, Japan
        • Shimamura Memorial Hospital
      • Tokyo, Japan
        • Toranomon Women's Clinic
      • Tokyo, Japan
        • Yokokura Clinic
      • Tokyo, Japan
        • Yukawa Women'S Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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 is a premenopausal Japanese woman aged 20 years or older at the time consent is obtained.

  2. The participant with endometriosis that falls under one of the following. However, in case of recurrence after surgery, it must be diagnosed again by either of the following.

    • The participant who has been diagnosed with endometriosis by Laparotomy or Laparoscopy.
    • The participant who has been confirmed ovarian chocolate cyst by Magnetic Resonance Imaging (MRI) or ultrasonic examination (vaginal, transabdominal or rectal).
    • The participant who has been diagnosed with clinical endometriosis and has the symptom of either induration of Douglas cavum, restriction of uterine mobility or pelvic tenderness confirmed by internal or rectal examination.
  3. The participant must have dysmenorrhea or pelvic pain associated with endometriosis, of which either 1 or both should be at least "moderate" as determined by the investigator or subinvestigator using the B&B scale.
  4. The participant must have maximum VAS score > 30 for pelvic pain associated with endometriosis.
  5. The participant has experienced regular menstrual cycles (25 to 38 days) that should include menstrual bleeding of at least 3 consecutive days (at least 3 regular menstrual cycles to be confirmed).
  6. The participant agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study.

Exclusion Criteria:

  1. The participant has the following drug usage:

    • Use of the following drugs within 24 weeks:bisphosphonate preparation or other investigational agent
    • Use of the following drugs within 16 weeks (for 1-, 3- and 6-month sustained-release preparations, within 20, 28 and 40 weeks, respectively): gonadotropin-releasing hormone (GnRH) analogues, danazol, or aromatase inhibitors.
    • Use of the following drugs within 8 weeks:dienogest, oral contraceptive or sex hormone preparations (norethindrone, norethisterone, medroxyprogesterone, estrogen, or other progestins, etc.)
    • Use of the following drugs (excluding drugs for external use and supplements) within 4 weeks :anti-coagulant drugs, anti-platelet drugs, tranexamic acid, selective estrogen receptor modulators, activated vitamin D preparations, other vitamin D preparations, calcitonin, ipriflavone, steroid hormones, vitamin K preparations, teriparatide, or denosumab
  2. The participant has received TAK-385 (including placebo) in a previous clinical study.
  3. The participant has ovarian chocolate cyst of 10 cm or more and over 40 years old at the time imaging test is performed.
  4. The participant has a history of panhysterectomy or bilateral oophorectomy.
  5. The participant has had markedly abnormal uterine bleeding or anovulatory bleeding, as determined by the investigator or subinvestigator.
  6. The participant has nondiagnosable abnormal genital bleeding.
  7. The participant has a current history of thyroid gland disorder with irregular menstruation, or has a potential for irregular menstruation due to thyroid gland disorder, as determined by the investigator or subinvestigator.
  8. The participant has uterine fibroid requiring treatment.
  9. The participant has lower abdominal pain due to irritable bowel syndrome or severe interstitial cystitis.
  10. The participant has a previous or current history of pelvic inflammatory disease within 8 weeks.
  11. The participant has a previous or current history of osteoporosis, osteopenia, or other metabolic bone diseases.
  12. The participant has a positive cervical cytology result [other than Negative for Intraepithelial Lesion or Malignancy (NILM) in accordance with the 2014 Bethesda system]. However, the following participant may participate in this study; Atypical Squamous Cells of Undetermined Significance (ASC-US) and negative by high-risk Human Papillomavirus (HPV) test. And furthermore, regarding the participant with negative cervical cytology result conducted within 1 year, she may participate in this study without additional test.
  13. The participant has a malignant tumor or a history of a malignant tumor within 5 years.
  14. The participant has clinically significant cardiovascular disease or uncontrollable hypertension.
  15. The participant is inappropriate for participation in this study based on 12-lead ECG findings, as determined by the investigator or subinvestigator.
  16. The participant has active liver disease or jaundice, or has Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) or total bilirubin > 1.5 times the upper limit of normal in the clinical laboratory tests.
  17. The participant has previous or current history of diseases considered to be inappropriate for participation in this study, including severe hepatic impairment, jaundice, renal impairment, cardiovascular disease, endocrine system disease, metabolic disorder, pulmonary disease, gastrointestinal disease, neural disease, urological disease, immune disease, or mental disorder (especially depression-like symptoms) or suicide attempt resulting from a mental disorder.
  18. The participant has a previous or current history of hypersensitivity to GnRH analogues, or has a previous or current history of severe hypersensitivity to other drugs.
  19. The participant is pregnant, lactating, or intending to become pregnant or to donate ova between the signing date of informed consent and 1 month after the end of the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: TAK-385
TAK-385 40 mg administered orally once daily before breakfast + Leuprorelin placebo administered subcutaneously once every 4 weeks
Drug: TAK-385
TAK-385 40 mg tablets + Leuprorelin acetate placebo injection
Other Names:
  • relugolix
Active Comparator: Leuprorelin acetate
TAK-385 placebo administered orally once daily before breakfast + Leuprorelin acetate 1.88 mg / 3.75 mg administered subcutaneously once every 4 weeks
Drug: Leuprorelin acetate
TAK-385 placebo tablets + Leuprorelin acetate 1.88 mg / 3.75 mg injection

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change of maximum Visual Analogue Scale (VAS) score for endometriosis associated pelvic pain
Time Frame: Baseline and the last 28 days of treatment period
Pelvic pain will be assessed using the VAS (0 - 100) as pain evaluation scale
Baseline and the last 28 days of treatment period

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change of mean VAS score for endometriosis associated pelvic pain
Time Frame: Baseline and the last 28 days of treatment period
Pelvic pain will be assessed using the VAS (0 - 100) as pain evaluation scale
Baseline and the last 28 days of treatment period
VAS score for endometriosis associated pelvic pain
Time Frame: Up to Week 24
Pelvic pain will be assessed using the VAS (0 - 100) as pain evaluation scale
Up to Week 24
Change of VAS score for endometriosis associated pelvic pain
Time Frame: Baseline and up to Week 24
Pelvic pain will be assessed using the VAS (0 - 100) as pain evaluation scale
Baseline and up to Week 24
VAS score for menstrual pain
Time Frame: Up to Week 24
Menstrual pain will be assessed using the VAS (0 - 100) as pain evaluation scale
Up to Week 24
Change of VAS score for menstrual pain
Time Frame: Baseline and up to Week 24
Menstrual pain will be assessed using the VAS (0 - 100) as pain evaluation scale
Baseline and up to Week 24
VAS score for endometriosis associated pelvic pain outside the menstruation period
Time Frame: Up to Week 24
Pelvic pain outside the menstruation period will be assessed using the VAS (0 - 100) as pain evaluation scale
Up to Week 24
Change of VAS score for endometriosis associated pelvic pain outside the menstruation period
Time Frame: Baseline and up to Week 24
Pelvic pain outside the menstruation period will be assessed using the VAS (0 - 100) as pain evaluation scale
Baseline and up to Week 24
VAS score for dyspareunia
Time Frame: Up to Week 24
Dyspareunia will be assessed using the VAS (0 - 100) as pain evaluation scale
Up to Week 24
Change of VAS score for dyspareunia
Time Frame: Baseline and up to Week 24
Dyspareunia will be assessed using the VAS (0 - 100) as pain evaluation scale
Baseline and up to Week 24
Adverse event
Time Frame: Up to Week 28
Up to Week 28
Bone mineral density
Time Frame: Up to Week 24
Up to Week 24
Serum concentrations of NTx (N-telopeptide)
Time Frame: Up to Week 24
Up to Week 24
Serum concentrations of BAP (Bone alkaline phosphatase)
Time Frame: Up to Week 24
Up to Week 24
Period from the last dose of study drug to return of menstrual cycles
Time Frame: From Week 24 to Week 28
From Week 24 to Week 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
ASKA Pharmaceutical Co., Ltd.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 8, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 12, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 28, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 24, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 26, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 30, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 11, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 10, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TAK-385/3-A

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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