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

NCT02655237 | Completed Phase 3 Results

• 3 other identifiers: TAK-385/CCT-002U1111-1178-0989JapicCTI-163128
• Study Type: interventional
• Target: 281
• Locations: 1 country
• Sites: 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.

Conditions

Uterine Fibroids

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Total PBAC Score of <10 From Week 6 to 12

  PBAC score was used to measure volume of menstrual blood loss. Participants used sanitary products designated by sponsor and recorded the numbers of tampons or towels used, clots and flooding in patient diary. Three diagrams used which represented a lightly, moderately stained or completely saturated pad/tampon. Following scores assigned: 1) 1, 5, or 20 points for each pad; 2) 1, 5, or 10 points for each tampon; 3) 1 or 5 points for each blood clot of \<1 cm/=1 cm/\>1 in longest diameter; 4) 5 points for each episode of flooding. The total PBAC score (sum of points) ranges from 0 to \>500.

  Week 6 to 12

Secondary Outcomes (16)

• Percentage of Participants With Total PBAC Score of <10 From Week 2 to 6

  Week 2 to 6

• Percentage of Participants With Total PBAC Score of <10 From Week 18 to 24

  Week 18 to 24

• Percentage of Participants With Total PBAC Score of <10 for 6 Weeks Before the Final Dose of Study Drug

  For 6 weeks before the final dose of study drug (up to Week 24)

• Percent Change From Baseline in Myoma Volumes at Weeks 2, 4, 8, 12 and 24

  Baseline, Weeks 2, 4, 8, 12 and 24

• Percent Change From Baseline in Uterine Volumes at Weeks 2, 4, 8, 12 and 24

  Baseline, Weeks 2, 4, 8, 12 and 24

Study Arms (2)

Relugolix 40 mg

EXPERIMENTAL

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.

Drug: Relugolix; Drug: Relugolix Placebo; Drug: Leuprorelin Placebo

Leuprorelin 1.88 mg or 3.75 mg

ACTIVE COMPARATOR

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.

Drug: Relugolix Placebo; Drug: Leuprorelin; Drug: Leuprorelin Placebo

Interventions

Relugolix DRUG

Relugolix tablets

Also known as: TAK-385

Relugolix 40 mg

Relugolix Placebo DRUG

Relugolix placebo-matching tablets

Leuprorelin 1.88 mg or 3.75 mg; Relugolix 40 mg

Leuprorelin DRUG

Leuprorelin injection

Leuprorelin 1.88 mg or 3.75 mg

Leuprorelin Placebo DRUG

Leuprorelin placebo-matching injections

Leuprorelin 1.88 mg or 3.75 mg; Relugolix 40 mg

Eligibility Criteria

• Age: 20 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In the opinion of the investigator or subinvestigator, the participant is capable of understanding and complying with protocol requirements.
• The participant signs and dates a written, informed consent form prior to the initiation of any study procedures.
• 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).
• The participant is a premenopausal Japanese woman.
• The participant is aged 20 years or older on the day of signing and dating the informed consent form.
• The participant has 1 or more measurable noncalcified myomas with the longest diameter of ≥ 3 cm confirmed by transvaginal ultrasound.
• 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.
• 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.
• 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.

You may not qualify if:

• 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).
• The participant has received relugolix (including placebo) in a previous clinical study.
• 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.
• 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.
• The participant has a known history of severe hypersensitivity or severe allergy to sanitary goods.
• The participant has lower abdominal pain due to irritable bowel syndrome or severe interstitial cystitis.
• 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 a previous or current history of pelvic inflammatory disease within 8 weeks prior to VISIT 1.
• 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).
• 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 a malignant tumor or a history of a malignant tumor within 5 years prior to VISIT 1.
• 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.
• 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).
• The participant has been treated with a bisphosphonate preparation within 24 weeks prior to VISIT 2.

Sponsors & Collaborators

• Takeda: lead

Study Sites (25)

Unknown Facility

Nagoya, Aichi-ken, Japan

Location

Unknown Facility

Matsudo, Chiba, Japan

Location

Unknown Facility

Kouriyama, Fukushima, Japan

Location

Unknown Facility

Ebetsu, Hokkaido, Japan

Location

Unknown Facility

Sapporo, Hokkaido, Japan

Location

Unknown Facility

Kako-gun, Hyōgo, Japan

Location

Unknown Facility

Nishinomiya, Hyōgo, Japan

Location

Unknown Facility

Kawasaki, Kanagawa, Japan

Location

Unknown Facility

Yamato, Kanagawa, Japan

Location

Unknown Facility

Yokohama, Kanagawa, Japan

Location

Unknown Facility

Ibaraki, Osaka, Japan

Location

Unknown Facility

Sakai, Osaka, Japan

Location

Unknown Facility

Suita, Osaka, Japan

Location

Unknown Facility

Yao, Osaka, Japan

Location

Unknown Facility

Bunkyo-ku, Tokyo, Japan

Location

Unknown Facility

Chiyoda-ku, Tokyo, Japan

Location

Unknown Facility

Chuou-ku, Tokyo, Japan

Location

Unknown Facility

Minato-ku, Tokyo, Japan

Location

Unknown Facility

Setagaya-ku, Tokyo, Japan

Location

Unknown Facility

Suginami-ku, Tokyo, Japan

Location

Unknown Facility

Taitou-ku, Tokyo, Japan

Location

Unknown Facility

Kagoshima, Japan

Location

Unknown Facility

Kyoto, Japan

Location

Unknown Facility

Osaka, Japan

Location

Unknown Facility

Saitama, Japan

Location

Related Publications (1)

• 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.

  PMID: 30741797 DERIVED

MeSH Terms

Conditions

Leiomyoma

Interventions

relugolix; Leuprolide

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Results Point of Contact

• Title: Medical Director, Clinical Science
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2016
• First Posted: January 13, 2016
• Study Start: March 5, 2016
• Primary Completion: May 17, 2017
• Study Completion: September 25, 2017
• Last Updated: March 22, 2019
• Results First Posted: March 22, 2019

Record last verified: 2018-12

Locations

JP (25)