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EndometriosisPhase 3NCT03931915

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

A Phase 3 study testing TAK-385 and Leuprorelin acetate in people with Endometriosis, run by ASKA Pharmaceutical Co., Ltd. at 41 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 20 years and older, women only
Conditions the study is for
Endometriosis
What is being tested?
TAK-385 and Leuprorelin acetate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
335 participants
Where
41 sitesJapan
Study dates
8 May 2019to 28 Sep 2020
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • The participant is a premenopausal Japanese woman aged 20 years or older at the time consent is obtained.
  • 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.
  • 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.
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  • The participant must have maximum VAS score > 30 for pelvic pain associated with endometriosis.
  • 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).
  • The participant agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study.

Who cannot join

  • 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
  • The participant has received TAK-385 (including placebo) in a previous clinical study.
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  • The participant has ovarian chocolate cyst of 10 cm or more and over 40 years old at the time imaging test is performed.
  • The participant has a history of panhysterectomy or bilateral oophorectomy.
  • The participant has had markedly abnormal uterine bleeding or anovulatory bleeding, as determined by the investigator or subinvestigator.
  • The participant has nondiagnosable abnormal genital bleeding.
  • 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.
  • The participant has uterine fibroid requiring treatment.
  • The participant has lower abdominal pain due to irritable bowel syndrome or severe interstitial cystitis.
  • The participant has a previous or current history of pelvic inflammatory disease within 8 weeks.
  • The participant has a previous or current history of osteoporosis, osteopenia, or other metabolic bone diseases.
  • 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.
  • The participant has a malignant tumor or a history of a malignant tumor within 5 years.
  • The participant has clinically significant cardiovascular disease or uncontrollable hypertension.
  • The participant is inappropriate for participation in this study based on 12-lead ECG findings, as determined by the investigator or subinvestigator.
  • 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.
  • 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.
  • 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.
  • 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.

Trial locations and contacts

41 sites in 1 country.

41 sites in 1 country

Japan41 sites

  • Chubu Rosai Hospital

    Aichi

  • Meitetsu Hospital

    Aichi

  • Aiiku Ladies Clinic

    Chiba

  • Chiba Aoba Municipal Hospital

    Chiba

  • Tokyo Bay Urayasu Ichikawa Medical Center

    Chiba

  • Tsujinaka Hospital Kashiwanoha

    Chiba

  • Fujito Clinic

    Hiroshima

  • Hashimoto Clinic

    Hokkaido

  • Tokeidai Memorial Hospital

    Hokkaido

  • Yoshio Obstetrics Gynecology Hospital

    Hokkaido

  • Shinsuma Hospital

    Hyōgo

  • Kagawa Prefectural Central Hospital

    Kagawa

  • Takamatsu Red Cross Hospital

    Kagawa

  • Fujisawa City Hospital

    Kanagawa

  • Rinkan Clinic

    Kanagawa

  • Second Kawasaki Saiwai Clinic

    Kanagawa

  • Tawada Ladies Clinic

    Kanagawa

  • Japanese Red Cross Kumamoto Hospital

    Kumamoto

  • Kurashiki Medical Clinic

    Okayama

  • Chayamachi Ladies Clinic

    Osaka

  • Hayakawa Clinic

    Osaka

  • Minami-Morimachi Ladies Clinic

    Osaka

  • Nomura Clinic Nanba

    Osaka

  • Rikako Ladies Clinic

    Osaka

  • Tanabe Ladies Clinic

    Osaka

  • Yoshimura Ladies Clinic

    Osaka

  • Dantsuka Clinic

    Saitama

  • Kashiwazaki Ladies Clinic

    Saitama

  • Maruyama Memorial General Hospital

    Saitama

  • Kusatsu General Hospital

    Shiga

  • Akasaka-Mitsuke Miyazaki Clinic

    Tokyo

  • Ginza Yoshida Hospital

    Tokyo

  • Hamada Hospital

    Tokyo

  • Ikebukuro Metroporitan Clinic

    Tokyo

  • NS Clinic

    Tokyo

  • Sei Women's Clinic

    Tokyo

  • Seijo Kinoshita Hospital

    Tokyo

  • Shimamura Memorial Hospital

    Tokyo

  • Toranomon Women's Clinic

    Tokyo

  • Yokokura Clinic

    Tokyo

  • Yukawa Women's Clinic

    Tokyo

Other trials in Japan

About this study

Official title: 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.

Read the 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.

Conditions
Endometriosis
Being tested
TAK-385, Leuprorelin acetate
Medical subject headings
Endometriosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TAK-385Drug

    Also called relugolix

    TAK-385 40 mg tablets + Leuprorelin acetate placebo injection

  • Leuprorelin acetateDrug

    TAK-385 placebo tablets + Leuprorelin acetate 1.88 mg / 3.75 mg injection

Study groups in NCT03931915
Study groupRoleWhat they receive
TAK-385ExperimentalTAK-385 40 mg administered orally once daily before breakfast + Leuprorelin placebo administered subcutaneously once every 4 weeks
Receives: Drug: TAK-385
Leuprorelin acetateActive comparatorTAK-385 placebo administered orally once daily before breakfast + Leuprorelin acetate 1.88 mg / 3.75 mg administered subcutaneously once every 4 weeks
Receives: Drug: Leuprorelin acetate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change of maximum Visual Analogue Scale (VAS) score for endometriosis associated pelvic pain

    Pelvic pain will be assessed using the VAS (0 - 100) as pain evaluation scale

    Measured: Baseline and the last 28 days of treatment period

Secondary outcomes (14)

  1. Change of mean VAS score for endometriosis associated pelvic pain

    Pelvic pain will be assessed using the VAS (0 - 100) as pain evaluation scale

    Measured: Baseline and the last 28 days of treatment period

  2. VAS score for endometriosis associated pelvic pain

    Pelvic pain will be assessed using the VAS (0 - 100) as pain evaluation scale

    Measured: Up to Week 24

  3. Change of VAS score for endometriosis associated pelvic pain

    Pelvic pain will be assessed using the VAS (0 - 100) as pain evaluation scale

    Measured: Baseline and up to Week 24

  4. VAS score for menstrual pain

    Menstrual pain will be assessed using the VAS (0 - 100) as pain evaluation scale

    Measured: Up to Week 24

  5. Change of VAS score for menstrual pain

    Menstrual pain will be assessed using the VAS (0 - 100) as pain evaluation scale

    Measured: Baseline and up to Week 24

  6. VAS score for endometriosis associated pelvic pain outside the menstruation period

    Pelvic pain outside the menstruation period will be assessed using the VAS (0 - 100) as pain evaluation scale

    Measured: Up to Week 24

  7. Change of VAS score for endometriosis associated pelvic pain outside the menstruation period

    Pelvic pain outside the menstruation period will be assessed using the VAS (0 - 100) as pain evaluation scale

    Measured: Baseline and up to Week 24

  8. VAS score for dyspareunia

    Dyspareunia will be assessed using the VAS (0 - 100) as pain evaluation scale

    Measured: Up to Week 24

  9. Change of VAS score for dyspareunia

    Dyspareunia will be assessed using the VAS (0 - 100) as pain evaluation scale

    Measured: Baseline and up to Week 24

  10. Adverse event

    Measured: Up to Week 28

  11. Bone mineral density

    Measured: Up to Week 24

  12. Serum concentrations of NTx (N-telopeptide)

    Measured: Up to Week 24

  13. Serum concentrations of BAP (Bone alkaline phosphatase)

    Measured: Up to Week 24

  14. Period from the last dose of study drug to return of menstrual cycles

    Measured: From Week 24 to Week 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Apr 2019
  2. Study start8 May 2019
  3. Primary completion12 Jun 2020
  4. Study completion28 Sep 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
335 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03931915
Sponsor's protocol ID
TAK-385/3-A
Status last verified
Jul 2020
First submitted
24 Apr 2019
Last updated
11 Dec 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Harada T, Osuga Y, Suzuki Y, Fujisawa M, Fukui M, Kitawaki J. Relugolix, an oral gonadotropin-releasing hormone receptor antagonist, reduces endometriosis-associated pain compared with leuprorelin in Japanese women: a phase 3, randomized, double-blind, noninferiority study. Fertil Steril. 2022 Mar;117(3):583-592. doi: 10.1016/j.fertnstert.2021.11.013. Epub 2021 Dec 8.

    PubMed 34895700

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing TAK-385 and Leuprorelin acetate in people with Endometriosis, run by ASKA Pharmaceutical Co., Ltd. at 41 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 41 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change of maximum Visual Analogue Scale (VAS) score for endometriosis associated pelvic pain (time frame: Baseline and the last 28 days of treatment period). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03931915, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2020.

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