A Phase 3 Study to Evaluate the Efficacy and Safety of Relugolix (TAK-385) 40 mg Compared With Leuprorelin in the Treatment of Uterine Fibroids

NCT ID: NCT02655237

Last Updated: 2019-03-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 281 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-05
• Study Completion Date: 2017-09-25

Brief Summary

The purpose of this study is to evaluate the efficacy of Relugolix (TAK-385) 40 mg administered orally once daily for 12 weeks, compared with leuprorelin injection (once every 4 weeks, 1.88 mg or 3.75 mg subcutaneously [SC]/time) in patients with uterine fibroids.

Detailed Description

The drug tested in this study was called Relugolix (TAK-385). Relugolix was tested to treat people who had uterine fibroids.

The study enrolled 281 patients. Participants received relugolix placebo and leuprorelin acetate placebo in run in period for 3 to 6 weeks. After run-in period, participants were randomly assigned (by chance, like flipping a coin) to one of the two treatment groups in 1:1 ratio:

• Relugolix 40 mg
• Leuprorelin 1.88 or 3.75 mg

Participants received relugolix tablets once daily along with leuprorelin 1.88 mg or 3.75 mg subcutaneous injection once in 4 weeks for 24 weeks in treatment period.

This multi-center trial was conducted in Japan. The overall time to participate in this study was approximately 32 to 40 weeks including run-in period of 3 to 6 weeks and a treatment period of 24 weeks. Participants will make multiple visits to the clinic, and a final visit 4 weeks after last dose of study drug for a follow-up assessment.

Conditions

Uterine Fibroids

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Relugolix 40 mg

Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.

Group Type: EXPERIMENTAL

Relugolix

Intervention Type: DRUG

Relugolix tablets

Relugolix Placebo

Intervention Type: DRUG

Relugolix placebo-matching tablets

Leuprorelin Placebo

Intervention Type: DRUG

Leuprorelin placebo-matching injections

Leuprorelin 1.88 mg or 3.75 mg

Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.

Group Type: ACTIVE_COMPARATOR

Relugolix Placebo

Intervention Type: DRUG

Relugolix placebo-matching tablets

Leuprorelin

Intervention Type: DRUG

Leuprorelin injection

Leuprorelin Placebo

Intervention Type: DRUG

Leuprorelin placebo-matching injections

Interventions

Relugolix

Relugolix tablets

Intervention Type: DRUG

Relugolix Placebo

Relugolix placebo-matching tablets

Intervention Type: DRUG

Leuprorelin

Leuprorelin injection

Intervention Type: DRUG

Leuprorelin Placebo

Leuprorelin placebo-matching injections

Intervention Type: DRUG

Other Intervention Names

TAK-385

Eligibility Criteria

Inclusion Criteria

1. In the opinion of the investigator or subinvestigator, the participant is capable of understanding and complying with protocol requirements.

2. The participant signs and dates a written, informed consent form prior to the initiation of any study procedures.

3. Prior to VISIT 1, the participant has a diagnosis of uterine fibroids confirmed by transvaginal ultrasound, abdominal ultrasound, magnetic resonance imaging (MRI), computed tomography (CT), or laparoscopy, and has never received any surgical treatment for the myoma (measurable noncalcified myoma with the longest diameter of ≥ 3 cm).

4. The participant is a premenopausal Japanese woman.

5. The participant is aged 20 years or older on the day of signing and dating the informed consent form.

6. The participant has 1 or more measurable noncalcified myomas with the longest diameter of ≥ 3 cm confirmed by transvaginal ultrasound.

7. The participant has experienced 1 or more regular menstrual cycles (25 to 38 days) immediately prior to VISIT 1 and that should include menstrual bleeding for at least 3 consecutive days.

8. The participant who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the study.

10. The participant has 1 or more measurable noncalcified myomas, with a longest diameter of ≥ 3 cm confirmed by transvaginal ultrasound (the same myoma should be measured as in Inclusion criterion #6).

11. The participant has a diagnosis of menorrhagia with a total Pictorial Blood loss Assessment Chart (PBAC) score of ≥ 120 in 1 menstrual cycle just before VISIT 3.

Exclusion Criteria

1. The participant has received any investigational compound within 24 weeks prior to the start of the administration of the study medication for the Run-in (VISIT 2).

2. The participant has received relugolix (including placebo) in a previous clinical study.

3. The participant is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.

4. The participant has a previous or current history of blood disorders (eg, thalassemia, sickle cells anemia, folic-acid deficiency, and coagulopathy), excluding (latent) iron-deficiency anemia.

5. The participant has a known history of severe hypersensitivity or severe allergy to sanitary goods.

6. The participant has lower abdominal pain due to irritable bowel syndrome or severe interstitial cystitis.

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 a previous or current history of pelvic inflammatory disease within 8 weeks prior to VISIT 1.

9. The participant has a positive Pap smear test result obtained within 1 year prior to VISIT 1 (if there are no previous test results, those who were judged positive in the test conducted before VISIT 2).

10. The participant has a history of panhysterectomy or bilateral oophorectomy.

11. The participant has had markedly abnormal uterine bleeding or anovulatory bleeding, as determined by the investigator or subinvestigator.

12. The participant has a malignant tumor or a history of a malignant tumor within 5 years prior to VISIT 1.

13. The participant has been treated with any of the following drugs (excluding drugs for external use and dietary supplements) within 4 weeks prior to VISIT 2: anti-coagulant drugs, anti-platelet drugs, tranexamic acid, selective estrogen receptor modulators (SERMs), activated vitamin D preparations, other vitamin D preparations, calcitonin, ipriflavone, steroid hormones, vitamin K preparations, teriparatide, or denosumab.

14. The participant has been treated with any of the following drugs within 8 weeks prior to VISIT 2: oral contraceptive or sex hormone preparations (norethindrone, norethisterone, medroxyprogesterone, estrogen, or other progestins), and within 16 weeks prior to VISIT 2: gonadotropin-releasing hormone (GnRH) analogues, dienogest, danazol, or aromatase inhibitors (for 1- and 3-month sustained-release preparations, within 20 and 28 weeks prior to VISIT 2, respectively).

15. The participant has been treated with a bisphosphonate preparation within 24 weeks prior to VISIT 2.

16. The participant has a previous or current history of hypersensitivity or allergies to leuprorelin, synthetic GnRH, GnRH agonists or GnRH antagonists, or has a previous or current history of severe hypersensitivity or severe allergy to other drugs.

17. The participant has nondiagnosable abnormal genital bleeding.

18. Female participant who is pregnant, lactating, or intending to become pregnant or to donate ova prior to the signing of informed consent, during the study period, or within 1 month after the end of the study.

19. The participant has a previous or current history of osteoporosis, osteopenia, or other metabolic bone diseases.

20. The participant has clinically significant cardiovascular disease (eg, myocardial infarction or unstable angina pectoris within 24 weeks prior to VISIT 1) or uncontrollable hypertension (eg, resting systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg at Screening and Run-in).

21. The participant is inappropriate for participation in this study based on standard 12-lead electrocardiogram (ECG) findings, as determined by the investigator or subinvestigator.

22. The participant has active liver disease or jaundice, or with alanine aminotransferase (ALT), aspartate aminotransferase (AST), or bilirubin (total bilirubin) > 1.5 times the upper limit of normal (ULN) in the clinical laboratory tests at VISITs 1 and 2.

23. 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, neurological disease, urological disease, immune disease, or mental disorder (especially depression-like symptoms) or suicide attempt resulting from a mental disorder.

24. The participant has a previous or current history of drug abuse (defined as any illicit drug use) or alcohol abuse.

25. The participant is inappropriate for participation in this study for other reasons, as determined by the investigator or subinvestigator.

• Minimum Eligible Age: 20 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Takeda

Locations

Nagoya, Aichi-ken, Japan

Matsudo, Chiba, Japan

Kouriyama, Fukushima, Japan

Ebetsu, Hokkaido, Japan

Sapporo, Hokkaido, Japan

Kako-gun, Hyōgo, Japan

Nishinomiya, Hyōgo, Japan

Kawasaki, Kanagawa, Japan

Yamato, Kanagawa, Japan

Yokohama, Kanagawa, Japan

Ibaraki, Osaka, Japan

Sakai, Osaka, Japan

Suita, Osaka, Japan

Yao, Osaka, Japan

Bunkyo-ku, Tokyo, Japan

Chiyoda-ku, Tokyo, Japan

Chuou-ku, Tokyo, Japan

Minato-ku, Tokyo, Japan

Setagaya-ku, Tokyo, Japan

Suginami-ku, Tokyo, Japan

Taitou-ku, Tokyo, Japan

Kagoshima, , Japan

Kyoto, , Japan

Osaka, , Japan

Saitama, , Japan

Countries

Japan

References

Osuga Y, Enya K, Kudou K, Tanimoto M, Hoshiai H. Oral Gonadotropin-Releasing Hormone Antagonist Relugolix Compared With Leuprorelin Injections for Uterine Leiomyomas: A Randomized Controlled Trial. Obstet Gynecol. 2019 Mar;133(3):423-433. doi: 10.1097/AOG.0000000000003141.

Reference Type: DERIVED

PMID: 30741797 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1178-0989

Identifier Type: REGISTRY

Identifier Source: secondary_id

JapicCTI-163128

Identifier Type: REGISTRY

Identifier Source: secondary_id

TAK-385/CCT-002

Identifier Type: -

Identifier Source: org_study_id