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Uterine FibroidsPhase 3NCT02655237

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

A Phase 3 study testing Relugolix and Leuprorelin in people with Uterine Fibroids, run by Takeda at 25 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 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. Read more about this study

Who is it for?
Ages 20 years and older, women only
Conditions the study is for
Uterine Fibroids
What is being tested?
Relugolix and Leuprorelin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
281 participants
Where
25 sitesJapan
Study dates
5 Mar 2016to 25 Sep 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • 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.
Show all 12Show fewer
  • 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 experienced regular menstrual cycles (25 to 38 days) immediately prior to VISIT 2 that should include menstrual bleeding of at least 3 consecutive days (at least 2 regular menstruation cycles to be confirmed by Inclusion criteria #7 and #9).
  • 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).
  • 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.
  • The participant has experienced regular menstrual cycles (25 to 38 days) after VISIT 1 that should include menstrual bleeding for at least 3 consecutive days (at least 3 regular menstruation cycles to be confirmed by Inclusion criteria #7, #9 and #12).

Who cannot join

  • 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.
Show all 25Show fewer
  • 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.
  • 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.
  • The participant has nondiagnosable abnormal genital bleeding.
  • 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.
  • The participant has a previous or current history of osteoporosis, osteopenia, or other metabolic bone diseases.
  • 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).
  • The participant is inappropriate for participation in this study based on standard 12-lead electrocardiogram (ECG) findings, as determined by the investigator or subinvestigator.
  • 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.
  • 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.
  • The participant has a previous or current history of drug abuse (defined as any illicit drug use) or alcohol abuse.
  • The participant is inappropriate for participation in this study for other reasons, as determined by the investigator or subinvestigator.

Trial locations and contacts

25 sites in 1 country.

25 sites in 1 country

Japan25 sites

  • Study site

    Bunkyo-ku, Tokyo

  • Study site

    Chiyoda-ku, Tokyo

  • Study site

    Chuou-ku, Tokyo

  • Study site

    Ebetsu, Hokkaido

  • Study site

    Ibaraki, Osaka

  • Study site

    Kagoshima

  • Study site

    Kako-gun, Hyōgo

  • Study site

    Kawasaki, Kanagawa

  • Study site

    Kouriyama, Fukushima

  • Study site

    Kyoto

  • Study site

    Matsudo, Chiba

  • Study site

    Minato-ku, Tokyo

  • Study site

    Nagoya, Aichi-ken

  • Study site

    Nishinomiya, Hyōgo

  • Study site

    Osaka

  • Study site

    Saitama

  • Study site

    Sakai, Osaka

  • Study site

    Sapporo, Hokkaido

  • Study site

    Setagaya-ku, Tokyo

  • Study site

    Suginami-ku, Tokyo

  • Study site

    Suita, Osaka

  • Study site

    Taitou-ku, Tokyo

  • Study site

    Yamato, Kanagawa

  • Study site

    Yao, Osaka

  • Study site

    Yokohama, Kanagawa

Other trials in Japan

About this study

Official title: A Multicenter, Randomized, Double-Blind, Parallel-Group, Phase 3 Study to Evaluate the Efficacy and Safety of Oral TAK-385 40 mg Compared With Leuprorelin in the Treatment of Uterine Fibroids

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.

Read the 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.

Being tested
Relugolix, Relugolix Placebo, Leuprorelin, Leuprorelin Placebo
Keywords
Drug Therapy
Medical subject headings
Leiomyoma

What participants receive

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

  • RelugolixDrug

    Also called TAK-385

    Relugolix tablets

  • Relugolix PlaceboDrug

    Relugolix placebo-matching tablets

  • LeuprorelinDrug

    Leuprorelin injection

  • Leuprorelin PlaceboDrug

    Leuprorelin placebo-matching injections

Study groups in NCT02655237
Study groupRoleWhat they receive
Relugolix 40 mgExperimentalRelugolix 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.
Receives: Drug: Relugolix; Drug: Relugolix Placebo; Drug: Leuprorelin Placebo
Leuprorelin 1.88 mg or 3.75 mgActive comparatorRelugolix 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.
Receives: Drug: Relugolix Placebo; Drug: Leuprorelin; Drug: Leuprorelin Placebo

What is being measured

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

  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.

    Measured: Week 6 to 12

Secondary outcomes (16)

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

    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.

    Measured: Week 2 to 6

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

    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.

    Measured: Week 18 to 24

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

    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.

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

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

    A transvaginal ultrasound was performed to determine myoma volumes. Only the largest myoma among those measurable at visit 1 was measured throughout the study. On the assumption that the myoma was spheroids, the myoma volumes were calculated using 3 diameters (D1, D2, and D3). D1: the longest diameter of the myoma; D2: the longest diameter of the myoma which was perpendicular to D1; D3: the diameter of the myoma which crossed the intersection of D1 and D2 (intersection "Z") and was perpendicular to D1/D2 plane. The formula used for calculation is Myoma volume= D1*D2*D3*π/6.

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

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

    A transvaginal ultrasound was performed for determination of uterine volumes. On the assumption that the uterus was spheroids, the uterine volumes were calculated using 3 diameters (D1, D2, and D3) measured as shown below: D1: the longest diameter of the uterus (unit of length: cm); D2: the longest diameter of the uterus which was perpendicular to D1 (unit of length: cm); D3: the diameter of the uterus which crossed the intersection of D1 and D2 (intersection "Z") and was perpendicular to D1/D2 plane (unit of length: cm). The formula used for calculation is Uterine volume=D1*D2*D3*π/6.

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

  6. Change From Baseline in Hemoglobin at Weeks 4, 8, 12, 16, 20, 24 and Follow up

    Anemia-related measurements consisted of hemoglobin, which were determined at the central laboratory.

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24 and Follow up (up to Week 28)

  7. Numerical Rating Scale (NRS) Score

    Pain symptoms were evaluated using the NRS score. NRS score is a self-reported instrument assessing pain from 0 to 10. Higher scores reflect greater level of pain.

    Measured: From Week 6 to 12, from Week 2 to 6, from Week 18 to 24, and for 6 weeks before the final dose (up to Week 24)

  8. Change From Baseline in Uterine Fibroid Symptom and Quality of Life (UFS-QOL)- Symptom Severity Score at Weeks 4, 8, 12, 16, 20, 24 and Follow-up

    UFS-QOL was a 37-item self-reporting tool for evaluating QOL in participants with uterine fibroid. It includes eight symptom-related questions and 29 HRQL questions across six subscales (concern, activities, energy/mood, control, self-consciousness, sexual function). The total symptom severity score is ranging from 0 to 100. The higher scores indicate greater severity.

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24 and Follow-up (up to Week 28)

  9. Change From Baseline in Uterine Fibroid Symptom and Quality of Life (UFS-QOL)- HRQL Total Scores at Weeks 4, 8, 12, 16, 20, 24 and Follow-up

    UFS-QOL was a 37-item self-reporting tool for evaluating QOL in participants with uterine fibroid. It includes eight symptom-related questions and 29 HRQL questions across six subscales (concern, activities, energy/mood, control, self-consciousness, sexual function). The total HRQL score is ranging from 0 to 100. The higher scores indicate better QOL.

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24 and Follow-up (up to Week 28)

  10. Number of Participants Who Had One or More Treatment Emergent Adverse Event (TEAE)

    An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

    Measured: Up to Week 28

  11. Number of Participants With Markedly Abnormal Values of Vital Signs

    Vital signs included sitting blood pressure (after the participant has rested for at least 5 minutes), body temperature (oral or tympanic measurement) (degree Celsius [°C]) and pulse (beats per minute [bpm]) is reported.

    Measured: Up to Week 28

  12. Number of Participants With TEAE Related to Weight

    Number of participants with TEAEs of which threshold was 5% or above in either treatment group related to weight was reported.

    Measured: Up to Week 28

  13. Number of Participants With TEAE Related to Standard 12-Lead ECGs

    Number of participants with TEAEs of which threshold was 5% or above in either treatment group related to ECG was reported.

    Measured: Up to Week 28

  14. Number of Participants With Markedly Abnormal Values of Laboratory Test

    Number of participants with any markedly abnormal values in laboratory tests collected throughout study is reported. WBC = White blood cells, AST = Aspartate Aminotransferase, ALT = Alanine Aminotransferase, GGT = gamma-glutamyl transferase, ULN = upper limit of normal or upper reference limit.

    Measured: Up to Week 28

  15. Number of Participants With TEAE (Bone Density Decreased) Related to Bone Mineral Density

    Number of participants with TEAEs of which threshold was 5% or above in either treatment group related to bone mineral density was reported.

    Measured: Up to Week 28

  16. Number of Participants With TEAE Related to Biochemical Bone Metabolism Markers

    Number of participants with TEAEs of which threshold was 5% or above in either treatment group related to biochemical bone metabolism markers was reported.

    Measured: Up 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 posted13 Jan 2016 (estimated)
  2. Study start5 Mar 2016
  3. Primary completion17 May 2017
  4. Study completion25 Sep 2017

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
281 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02655237
Sponsor's protocol ID
TAK-385/CCT-002
Other IDs
U1111-1178-0989, JapicCTI-163128
Status last verified
Dec 2018
First submitted
12 Jan 2016
Last updated
22 Mar 2019
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 30741797

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Relugolix and Leuprorelin in people with Uterine Fibroids, run by Takeda at 25 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 12 inclusion and 25 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 22 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 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?

Yes. Results are posted in the registry (first posted 22 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Percentage of Participants With Total PBAC Score of <10 From Week 6 to 12 (time frame: Week 6 to 12). 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 NCT02655237, 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 22 Mar 2019; AzTrials last refreshed its copy on 28 Oct 2026.

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