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A Placebo-Controlled, Phase 3 Study of Relugolix (TAK-385) 40 mg in the Treatment of Pain Symptoms Associated With Uterine Fibroids

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02655224
Recruitment Status : Completed
First Posted : January 13, 2016
Results First Posted : March 22, 2019
Last Update Posted : March 22, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda

Tracking Information
First Submitted Date  ICMJE January 12, 2016
First Posted Date  ICMJE January 13, 2016
Results First Submitted Date  ICMJE May 16, 2018
Results First Posted Date  ICMJE March 22, 2019
Last Update Posted Date March 22, 2019
Actual Study Start Date  ICMJE March 26, 2016
Actual Primary Completion Date May 16, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 25, 2018)
Percentage of Participants With a Maximum NRS Score of 1 or Less During the 28 Days Before the Final Dose of Study Drug [ Time Frame: For 28 days before the final dose of study drug (up to Week 12) ]
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. The percentage of participants with a score of 1 or less is reported.
Original Primary Outcome Measures  ICMJE
 (submitted: January 12, 2016)
Proportion of participants with a maximum NRS score of 1 or less during the 28 days before the final dose of study drug (Week 12) [ Time Frame: Week 12 ]
NRS score is a 11-item self-reported instrument assessing pain. It includes 11 items from 0 (No Pain), 1-3 (Mild Pain), 4-6 (Moderate Pain), and 7-10 (Severe Pain). Higher scores reflect greater level of pain.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 25, 2018)
  • Percentage of Participants With a Maximum NRS Score of 0 During the 28 Days Before the Final Dose of Study Drug [ Time Frame: For 28 days before the final dose of study drug (up to Week 12) ]
    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. The percentage of participants with a score of 0 is reported.
  • Mean NRS Score During the 28 Days Before the Final Dose of Study Drug [ Time Frame: For 28 days before the final dose of study drug (up to Week 12) ]
    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.
  • Percentage of Days Without Pain Symptoms (NRS = 0) During the 28 Days Before the Final Dose of Study Drug [ Time Frame: For 28 days before the final dose of study drug (up to Week 12) ]
    Percentage of day without pain symptoms (NRS = 0) was reported. Number of days without pain symptoms is determined by a zero score on the NRS. 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. Percentage of days without pain symptoms (NRS=0) during the 28 days before the final dose of study drug (%) = [(number of days without pain symptoms (NRS=0) during the last 28 days of the treatment)/(number of days with available data during the last 28 days of the treatment)]*100.
  • Percentage of Participants With Maximum NRS Score of 1 or Less From Day 1 to 28, From Day 29 to 56, and From Day 57 to 84 [ Time Frame: Day 1 to 28, Day 29 to 56, and Day 57 to 84 ]
    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. The percentage of participants with a score of 1 or less is reported.
  • Percentage of Participants With a Maximum NRS Score of 0 From Day 1 to 28, From Day 29 to 56, and From Day 57 to 84 [ Time Frame: Day 1 to 28, Day 29 to 56, and Day 57 to 84 ]
    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. The percentage of participants with a score of 0 is reported.
  • Mean NRS Score From Day 1 to 28, From Day 29 to 56, and From Day 57 to 84 [ Time Frame: Day 1 to 28, Day 29 to 56, and Day 57 to 84 ]
    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.
  • Percentage of Days Without Pain Symptoms (NRS = 0) From Day 1 to 28, From Day 29 to 56, and From Day 57 to 84 [ Time Frame: Day 1 to 28, Day 29 to 56, and Day 57 to 84 ]
    Percentage of day without pain symptoms (NRS = 0) was reported. Number of days without pain symptoms is determined by a zero score on the NRS. 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. Percentage of days without pain symptoms (NRS=0) (%) = [(number of days without pain symptoms (NRS=0) during the last 28 days of the treatment)/(number of days with available data during the last 28 days of the treatment)]*100.
  • Number of Participants Reporting Who Had One or More Treatment-emergent Adverse Event (TEAE) [ Time Frame: Up to Week 16 ]
    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.
  • Number of Participants With Markedly Abnormal Values of Vital Signs [ Time Frame: Up to Week 16 ]
    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]) are reported.
  • Number of Participants With TEAEs Related to Weight [ Time Frame: Up to Week 16 ]
    Number of participants with TEAEs of which threshold was 5% or above in either treatment group related to weight was reported.
  • Number of Participants With TEAEs Related to Standard 12-lead Electrocardiogram (ECG) [ Time Frame: Up to Week 16 ]
    Number of participants with TEAEs of which threshold was 5% or above in either treatment group related to ECG was reported.
  • Number of Participants With Markedly Abnormal Values of Laboratory Tests [ Time Frame: Up to Week 16 ]
    Number of participants with any markedly abnormal values in laboratory tests collected throughout study is reported. WBC = White blood cells, GGT = gamma-glutamyl transferase, LLN = lower limit of normal or lower reference limit, ULN = upper limit of normal or upper reference limit.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 12, 2016)
  • Proportion of participants with a maximum NRS score of 0 during the 28 days before the final dose of study drug (Week 12) [ Time Frame: Up to 28 days before Week 12 ]
    NRS score is a 11-item self-reported instrument assessing pain. It includes 11 items from 0 (No Pain), 1-3 (Mild Pain), 4-6 (Moderate Pain), and 7-10 (Severe Pain). Higher scores reflect greater level of pain.
  • Mean NRS score during the 28 days before the final dose of study drug (Week 12) [ Time Frame: Up to 28 days before Week 12 ]
    NRS score is a 11-item self-reported instrument assessing pain. It includes 11 items from 0 (No Pain), 1-3 (Mild Pain), 4-6 (Moderate Pain), and 7-10 (Severe Pain). Higher scores reflect greater level of pain.
  • Number of days without pain symptoms (NRS = 0) during the 28 days before the final dose of study drug [ Time Frame: Up to 28 days before Week 12 ]
    Number of days without pain symptoms is determined from zero score in NRS. NRS score is a 11-item self-reported instrument assessing pain. It includes 11 items from 0 (No Pain), 1-3 (Mild Pain), 4-6 (Moderate Pain), and 7-10 (Severe Pain). Higher scores reflect greater level of pain.
  • Number of Participants Reporting One or More Treatment-emergent Adverse Events [ Time Frame: Up to 28 days from Week 12 ]
    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.
  • Number of Participants who have AEs related to Vital Signs [ Time Frame: Up to 28 days from Week 12 ]
    Vital signs included sitting blood pressure (after the participant has rested for at least 5 minutes), body temperature (oral or tympanic measurement) (degree Celsius) and pulse (bpm).
  • Number of Participants who have AEs related to Body Weight [ Time Frame: Up to 28 days from Week 12 ]
    Number of participants with any markedly abnormal values in participant's weight collected throughout study.
  • Number of Participants who have AEs related to Standard 12-lead Electrocardiogram (ECG) [ Time Frame: Up to 28 days from Week 12 ]
    Number of participants with any markedly abnormal values in electrocardiograms collected throughout study.
  • Number of Participants who have AEs related to Laboratory Tests [ Time Frame: Up to 28 days from Week 12 ]
    Number of participants with any markedly abnormal values in laboratory tests collected throughout study.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Placebo-Controlled, Phase 3 Study of Relugolix (TAK-385) 40 mg in the Treatment of Pain Symptoms Associated With Uterine Fibroids
Official Title  ICMJE A Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Oral TAK-385 40 mg in the Treatment of Pain Symptoms Associated With Uterine Fibroids
Brief Summary The purpose of this study is to evaluate the efficacy and safety of Relugolix (TAK-385) in patients having pain symptoms associated with uterine fibroids.
Detailed Description

The drug being tested in this study is called relugolix (TAK-385). Relugolix is being tested to treat people who have uterine fibroids.

The study enrolled 65 patients. Participants received relugolix placebo in run in period for 3 to 6 weeks. After run-in period, participants were randomly assigned to one of the two treatment groups in 1:1 ratio:

  1. Relugolix 40 mg
  2. Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient

All participants were asked to take one tablet at the same time each day throughout the study.

This multi-center trial was conducted in Japan. The overall time to participate in this study was 20 to 28 weeks, including run-in period of 3 to 6 weeks and a treatment period of 12 weeks. Participants made multiple visits to the clinic, and 4 weeks after last dose of study drug for a follow-up assessment.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Uterine Fibroids
Intervention  ICMJE
  • Drug: Relugolix
    Relugolix Tablets
    Other Name: TAK-385
  • Drug: Relugolix placebo
    Relugolix placebo-matching tablets
Study Arms  ICMJE
  • Experimental: Relugolix 40 mg
    Relugolix placebo-matching tablet, orally, once daily before breakfast for 3 to 6 weeks in the run-in period, followed by relugolix 40 mg, tablet, orally once daily before breakfast for 12 weeks.
    Intervention: Drug: Relugolix
  • Placebo Comparator: Placebo
    Relugolix placebo-matching tablet, orally, once daily before breakfast for 3 to 6 weeks in the run-in period, followed by relugolix placebo-matching tablet, orally once daily before breakfast for 12 weeks.
    Intervention: Drug: Relugolix placebo
Publications * Osuga Y, Enya K, Kudou K, Hoshiai H. Relugolix, a novel oral gonadotropin-releasing hormone antagonist, in the treatment of pain symptoms associated with uterine fibroids: a randomized, placebo-controlled, phase 3 study in Japanese women. Fertil Steril. 2019 Nov;112(5):922-929.e2. doi: 10.1016/j.fertnstert.2019.07.013. Epub 2019 Oct 6.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 25, 2018)
65
Original Estimated Enrollment  ICMJE
 (submitted: January 12, 2016)
64
Actual Study Completion Date  ICMJE May 19, 2017
Actual Primary Completion Date May 16, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Inclusion Criteria for Entering the Screening Period (at VISIT 1)

  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 a 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 a 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.

    Inclusion Criteria for Entering the Run-in Period (at VISIT 2)

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

    Inclusion Criteria for Entering the Treatment Period (at VISIT 3)

  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 in Inclusion criterion #6).
  11. The participant has a maximum Numerical Rating Scale (NRS) score of ≥4 during 1 menstrual cycle just before VISIT 3.
  12. The participant has pain symptoms associated with uterine fibroids for at least 2 days during 1 menstrual cycle just before VISIT 3.
  13. 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 #13).

Exclusion Criteria:

  1. The participant has received any investigational compound within 24 weeks prior to the start of the administration of the study drug for the day of first menstruation after VISIT 1.
  2. The participant has received relugolix (including placebo) in a previous clinical study.
  3. The participant is an immediate family member or 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, or sibling) or may consent under duress.
  4. The participant has lower abdominal pain due to irritable bowel syndrome or severe interstitial cystitis.
  5. 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.
  6. The participant has a previous or current history of pelvic inflammatory disease within 8 weeks prior to VISIT 1.
  7. 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).
  8. The participant has a history of panhysterectomy or bilateral oophorectomy.
  9. The participant has had markedly abnormal uterine bleeding or anovulatory bleeding, as determined by the investigator or subinvestigator.
  10. The participant has a malignant tumor or a history of a malignant tumor within 5 years prior to VISIT 1.
  11. The participant has been treated with selective estrogen receptor modulators (SERMs) (excluding drugs for external use and dietary supplements) within 4 weeks prior to VISIT 2.
  12. 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).
  13. The participant has a previous or current history of severe hypersensitivity or severe allergies to drugs.
  14. The participant has nondiagnosable abnormal genital bleeding.
  15. 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.
  16. 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 Period).
  17. The participant is ineligible for this study based on standard 12-lead electrocardiogram (ECG) findings, as determined by the investigator or subinvestigator.
  18. 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 VISIT 1 and 2.
  19. The participant has a previous or current history of diseases considered to be ineligible for 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, mental disorder (especially depression-like symptoms) and suicide attempt resulting from a mental disorder.
  20. The participant has a previous or current history of drug abuse (defined as any illicit drug use) or alcohol abuse.
  21. The participant is ineligible for this study for other reasons, as determined by the investigator or subinvestigator.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02655224
Other Study ID Numbers  ICMJE TAK-385-3008
U1111-1178-1086 ( Registry Identifier: WHO )
JapicCTI-163127 ( Registry Identifier: JapicCTI )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Takeda
Study Sponsor  ICMJE Takeda
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Study Director Takeda
PRS Account Takeda
Verification Date December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP