Clinical Trials List
Protocol NumberMVT-601-3201
NCT Number(ClinicalTrials.gov Identfier)NCT03085095
2017-08-01 - 2020-12-31
Phase III
Terminated4
ICD-10C61
Malignant neoplasm of prostate
ICD-9185
Malignant neoplasm of prostate
HERO: A Multinational Phase 3 Randomized, Open-label, Parallel Group Study to Evaluate the Safety and Efficacy of Relugolix in Men with Advanced Prostate Cancer
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Trial Applicant
PPD DEVELOPMENT (HK) LIMITED
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Sponsor
Myovant Sciences GmbH
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Hsiao-Jen Chung Division of Urology
- Tzu-chun Wei Division of Urology
- Yen-Hwa Chang Division of Urology
- 朱力行 Division of Nuclear Medicine
- 沈書慧 Division of Radiology
- Yi-Hsiu Huang Division of Urology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 吳勝堂 Division of Urology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- CHUNG-HSIN CHEN Division of Urology
- Ying-Chun Shen Division of Hematology & Oncology
- Chia-Hsien Chen Division of Radiology
- - - Division of Urology
- Yu-Chieh Tsai Division of Hematology & Oncology
- YEN-HENG LIN Division of Radiology
- - - Division of Urology
- Hong-Chiang Chang Division of Urology
- CHING-CHU LU Division of Nuclear Medicine
- YU-CHUAN LU Division of Urology
- JHE-CYUAN GUO Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
- Hsiang Ying Lee Division of Urology
- Tsung-Yi Huang Division of Urology
- 黃俊農 Division of Urology
- 李政學 Division of Urology
- 耿俊閎 Division of Urology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Advanced Prostate Cancer
Objectives
Primary:
• To evaluate the ability of relugolix to achieve and maintain serum
testosterone suppression to castrate levels (≤ 50 ng/dL [1.7 nmol/L])
in men with androgen-sensitive advanced prostate cancer.
Secondary:
• To evaluate the time course and change in serum testosterone during
treatment with relugolix;
• To evaluate the time course and magnitude of prostate-specific
antigen (PSA) reduction during treatment with relugolix;
• To evaluate testosterone recovery following discontinuation of relugolix;
• To evaluate quality of life using validated patient-reported outcome instruments;
• To evaluate the safety of relugolix 120 mg once daily in men with
androgen-sensitive advanced prostate cancer;
• To evaluate the effect of relugolix and leuprolide acetate on
endocrine pharmacodynamic parameters;
• To collect relugolix plasma concentration data to further evaluate
relugolix population pharmacokinetics (PK) and the relationship
between relugolix exposure and serum testosterone; and
• To characterize the relugolix plasma PK parameters in a subset of patients from China and Japan.
Test Drug
Relugolix 120 mg
Active Ingredient
Relugolix
Dosage Form
Tablet
Dosage
120 mg
Endpoints
Primary Outcome Measures :
Sustained Castration Rate [ Time Frame: From Week 5 Day 1 (Day 29) to Week 49 Day 1 (Day 337) ]
Sustained castration rate defined as the cumulative probability of testosterone suppression to < 50 nanogram (ng)/deciliter (dL). The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.
The lower bound of the 95% confidence interval (CI) for the cumulative probability of sustained testosterone suppression in the relugolix treatment group must have been ≥ 90% to meet evaluation criteria for efficacy.
Secondary Outcome Measures :
Castration Rate At Week 1 Day 4 [ Time Frame: Week 1 Day 4 (Day 4) ]
Castration rate was defined as the cumulative probability of testosterone suppression to < 50 ng/dL. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.
Castration Rate At Week 3 Day 1 [ Time Frame: Week 3 Day 1 (Day 15) ]
Castration rate was defined as the cumulative probability of testosterone suppression to < 50 ng/dL. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.
Confirmed Prostate-specific Antigen (PSA) Response Rate [ Time Frame: Week 3 Day 1 (Day 15) and Week 5 Day 1 (Day 29) ]
Confirmed PSA response defined as > 50% reduction in PSA from baseline at Week 3 Day 1 followed with confirmation at Week 5 Day 1.
Profound Castration Rate At Week 3 Day 1 (Day 15) [ Time Frame: Week 3 Day 1 (Day 15) ]
Castration rate defined as the cumulative probability of testosterone suppression to < 20 ng/dL. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.
Follicle-stimulating Hormone (FSH) Level [ Time Frame: Week 25 Day 1 (Day 169) ]
To evaluate the effect of relugolix and leuprolide acetate on FSH suppression.
PSA Response Rate At Week 3 Day 1 [ Time Frame: Week 3 Day 1 (Day 15) ]
PSA response defined as > 50% reduction in PSA from baseline. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.
PSA Response Rate At Week 5 Day 1 [ Time Frame: Week 5 Day 1 (Day 29) ]
PSA response defined as > 50% reduction in PSA from baseline. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.
Testosterone Recovery Rate [ Time Frame: Day 90 follow-up ]
The cumulative probability of testosterone recovery back to > 280 ng/dL (lower limit of the normal range), back to ≥ 50 ng/dL (definition of castration), and back to > 280 ng/dL or baseline at 90 days after drug discontinuation was assessed. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.
Sustained Profound Castration Rate From Week 5 Day 1 Through Week 49 Day 1 [ Time Frame: Week 5 Day 1 (Day 29) through Week 49 Day 1 (Day 337) ]
Sustained profound castration rate was defined as the cumulative probability of testosterone suppression to < 20 ng/dL. The rate was estimated by the Kaplan-Meier method and reported as percentage of participants.
Profound Castration Rate At Week 1 Day 4 (Day 4) [ Time Frame: At Week 1 Day 4 (Day 4) ]
Castration rate defined as the cumulative probability of testosterone suppression to < 20 ng/dL. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.
Sustained Profound Castration Rate From Week 25 Day 1 Through Week 49 Day 1 [ Time Frame: Week 25 Day 1 (Day 169) through Week 49 Day 1 (Day 337) ]
Sustained profound castration rate was defined as the cumulative probability of testosterone suppression to < 20 ng/dL. The rate was estimated by the Kaplan-Meier method and reported as percentage of participants.
Undetectable PSA Rate [ Time Frame: Week 25 Day 1 (Day 169) ]
Defined as the proportion of participants with PSA concentration < 0.02 ng/milliliter (mL).The rate was estimated by the Kaplan-Meier method and reported as percentage of participants.
Rate Of PSA Progression-free Survival [ Time Frame: Week 49 Day 1 (Day 337) ]
PSA progression was defined as the first increase in PSA of 25% or greater and 2 ng/mL or greater above the nadir with confirmation by a second consecutive PSA measurement at least 3 weeks later. For participants without declining PSA from baseline, a PSA increase of ≥ 25% and ≥ 2 ng/mL from baseline beyond 12 weeks was considered PSA progression. The rate of progression-free survival was estimated using the Kaplan-Meier method and reported as percentage of participants.
Change From Baseline In Quality Of Life (QoL) Total Score As Assessed By The Global Health Domain Of The European Organisation Of Research And Treatment Of Cancer (EORTC)-Quality Of Life Questionnaire (QLQ)-C30 [ Time Frame: Baseline, Week 49 Day 1 (Day 337) ]
The EORTC QLQ-C30 core measurement was used to capture distal outcomes, including physical, social functioning, and overall health-related quality of life. The questionnaire incorporates 30 questions comprising nine multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social); 3 symptom scales (fatigue, pain, and nausea and vomiting); and a global health and quality of life scale. All raw domain scores are linearly transformed to a 0-100 scale. The global health and quality of life domain is presented. An increase in activity or functioning scores indicates improvement (higher/healthier level of functioning) and a decrease in symptom scores indicates improvement (lower level of symptoms/problems).
Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 [ Time Frame: Baseline, Week 49 Day 1 (Day 337) ]
The EORTC QLQ-C30 core measurement was used to capture distal outcomes, including physical, social functioning, and overall health-related quality of life. The questionnaire incorporates 30 questions comprising nine multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social); 3 symptom scales (fatigue, pain, and nausea and vomiting); and a global health and quality of life scale. All raw domain scores are linearly transformed to a 0-100 scale. All domains except for the global health and quality are presented. An increase in activity or functioning scores indicates improvement (higher/healthier level of functioning) and a decrease in symptom scores indicates improvement (lower level of symptoms/problems).
Change From Baseline In QoL Total Score As Assessed By The EORTC-QLQ-PR25 Sexual Activity And Functioning And Hormonal-Treatment-Related Symptom Subdomains [ Time Frame: Baseline, Week 49 Day 1 (Day 337) ]
Subscales for assessment of hormonal treatment-related symptoms (6 items) and sexual activity and function (6 items) from the EORTC-QLQ-PR25 25-item prostate cancer module of the EORTC are presented. Questions used 4 point scale (1 'Not at all' to 4 'Very much'). All raw domain scores are linearly transformed to a 0-100 scale. An increase in activity or functioning scores indicates improvement (higher/healthier level of functioning) and a decrease in symptom scores indicates improvement (lower level of symptoms/problems).
Change From Baseline In QoL Total Score For Urinary And Bowel Symptoms Domains As Assessed By The EORTC-QLQ-PR25 [ Time Frame: Baseline, Week 49 Day 1 (Day 337) ]
Subscale assessments of urinary symptoms (9 items) and bowel symptoms (4 items) from the EORTC-QLQ-PR25 25-item prostate cancer module of the EORTC are presented. Questions used 4 point scale (1 'Not at all' to 4 'Very much'). All raw domain scores are linearly transformed to a 0-100 scale. A decrease in symptom scores indicates improvement (lower level of symptoms/problems).
Change From Baseline In QoL Total Score As Assessed By The European Quality Of Life 5-Dimension 5-Level Questionnaire (EuroQoL EQ-5D-5L) [ Time Frame: Baseline, Week 49 Day 1 (Day 337) ]
The EuroQoL EQ-5D-5L comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 5 levels: no problems (1 as numerical score), slight problems (2 as numerical score), moderate problems (3 as numerical score), severe problems (4 as numerical score), and extreme problems (5 as numerical score). The total score ranges from 0 to 100. A decrease in score indicates improvement.
Percent Change From Baseline In Serum Concentrations Of Luteinizing Hormone [ Time Frame: Week 1 Day 4 (Day 4), Week 5 Day 1 (Day 29), Week 25 Day 1 (Day 169), and Week 49 Day 1 (Day 337) ]
Blood samples were collected from participants for hormonal measurements.
Percent Change From Baseline In Serum Concentrations Of FSH [ Time Frame: Week 1 Day 4 (Day 4), Week 5 Day 1 (Day 29), Week 25 Day 1 (Day 169), and Week 49 Day 1 (Day 337) ]
Blood samples were collected from participants for hormonal measurements.
Percent Change From Baseline In Serum Concentrations Of Dihydrotestosterone [ Time Frame: Week 5 Day 1 (Day 29), Week 25 Day 1 (Day 169), and Week 49 Day 1 (Day 337) ]
Blood samples were collected from participants for hormonal measurements.
Percent Change From Baseline In Serum Concentrations Of Sex Hormone-Binding Globulin [ Time Frame: Week 5 Day 1 (Day 29), Week 25 Day 1 (Day 169), and Week 49 Day 1 (Day 337) ]
Blood samples were collected from participants for hormonal measurements.
Maximum Observed Plasma Concentration (Cmax) Of Relugolix [ Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1 and Week 2 ]
The Cmax of relugolix was determined for single and repeat doses in subsets of participants from Japan. Single dose pharmacokinetics (PK) was assessed on Day 1 following an initial 360 mg dose of relugolix. Repeat dose PK was assessed following repeat dosing of relugolix 120 mg once daily for 2 weeks.
Area Under The Concentration-Time Curve (AUC0-τ) Of Relugolix [ Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1 and Week 2 ]
The AUC0-τ of relugolix was determined for single and repeat doses in subsets of participants from Japan. Single dose PK was assessed on Day 1 following an initial 360 mg dose of relugolix. Repeat dose PK was assessed following repeat dosing of relugolix 120 mg once daily for 2 weeks.
Time To Maximum Observed Plasma Concentration (Tmax) Of Relugolix [ Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1 and Week 2 ]
The Tmax of relugolix was determined for single and repeat doses in subsets of participants from Japan. Single dose PK was assessed on Day 1 following an initial 360 mg dose of relugolix. Repeat dose PK was assessed following repeat dosing of relugolix 120 mg once daily for 2 weeks.
Other Outcome Measures:
Percentage of Participants Who Experienced Major Adverse Cardiovascular Events (MACE) [ Time Frame: From Week 5 Day 1 (Day 29) to Week 49 Day 1 (Day 337) ]
MACE were defined as nonfatal myocardial infarction, nonfatal stroke, and death from any cause.
Sustained Castration Rate [ Time Frame: From Week 5 Day 1 (Day 29) to Week 49 Day 1 (Day 337) ]
Sustained castration rate defined as the cumulative probability of testosterone suppression to < 50 nanogram (ng)/deciliter (dL). The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.
The lower bound of the 95% confidence interval (CI) for the cumulative probability of sustained testosterone suppression in the relugolix treatment group must have been ≥ 90% to meet evaluation criteria for efficacy.
Secondary Outcome Measures :
Castration Rate At Week 1 Day 4 [ Time Frame: Week 1 Day 4 (Day 4) ]
Castration rate was defined as the cumulative probability of testosterone suppression to < 50 ng/dL. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.
Castration Rate At Week 3 Day 1 [ Time Frame: Week 3 Day 1 (Day 15) ]
Castration rate was defined as the cumulative probability of testosterone suppression to < 50 ng/dL. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.
Confirmed Prostate-specific Antigen (PSA) Response Rate [ Time Frame: Week 3 Day 1 (Day 15) and Week 5 Day 1 (Day 29) ]
Confirmed PSA response defined as > 50% reduction in PSA from baseline at Week 3 Day 1 followed with confirmation at Week 5 Day 1.
Profound Castration Rate At Week 3 Day 1 (Day 15) [ Time Frame: Week 3 Day 1 (Day 15) ]
Castration rate defined as the cumulative probability of testosterone suppression to < 20 ng/dL. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.
Follicle-stimulating Hormone (FSH) Level [ Time Frame: Week 25 Day 1 (Day 169) ]
To evaluate the effect of relugolix and leuprolide acetate on FSH suppression.
PSA Response Rate At Week 3 Day 1 [ Time Frame: Week 3 Day 1 (Day 15) ]
PSA response defined as > 50% reduction in PSA from baseline. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.
PSA Response Rate At Week 5 Day 1 [ Time Frame: Week 5 Day 1 (Day 29) ]
PSA response defined as > 50% reduction in PSA from baseline. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.
Testosterone Recovery Rate [ Time Frame: Day 90 follow-up ]
The cumulative probability of testosterone recovery back to > 280 ng/dL (lower limit of the normal range), back to ≥ 50 ng/dL (definition of castration), and back to > 280 ng/dL or baseline at 90 days after drug discontinuation was assessed. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.
Sustained Profound Castration Rate From Week 5 Day 1 Through Week 49 Day 1 [ Time Frame: Week 5 Day 1 (Day 29) through Week 49 Day 1 (Day 337) ]
Sustained profound castration rate was defined as the cumulative probability of testosterone suppression to < 20 ng/dL. The rate was estimated by the Kaplan-Meier method and reported as percentage of participants.
Profound Castration Rate At Week 1 Day 4 (Day 4) [ Time Frame: At Week 1 Day 4 (Day 4) ]
Castration rate defined as the cumulative probability of testosterone suppression to < 20 ng/dL. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.
Sustained Profound Castration Rate From Week 25 Day 1 Through Week 49 Day 1 [ Time Frame: Week 25 Day 1 (Day 169) through Week 49 Day 1 (Day 337) ]
Sustained profound castration rate was defined as the cumulative probability of testosterone suppression to < 20 ng/dL. The rate was estimated by the Kaplan-Meier method and reported as percentage of participants.
Undetectable PSA Rate [ Time Frame: Week 25 Day 1 (Day 169) ]
Defined as the proportion of participants with PSA concentration < 0.02 ng/milliliter (mL).The rate was estimated by the Kaplan-Meier method and reported as percentage of participants.
Rate Of PSA Progression-free Survival [ Time Frame: Week 49 Day 1 (Day 337) ]
PSA progression was defined as the first increase in PSA of 25% or greater and 2 ng/mL or greater above the nadir with confirmation by a second consecutive PSA measurement at least 3 weeks later. For participants without declining PSA from baseline, a PSA increase of ≥ 25% and ≥ 2 ng/mL from baseline beyond 12 weeks was considered PSA progression. The rate of progression-free survival was estimated using the Kaplan-Meier method and reported as percentage of participants.
Change From Baseline In Quality Of Life (QoL) Total Score As Assessed By The Global Health Domain Of The European Organisation Of Research And Treatment Of Cancer (EORTC)-Quality Of Life Questionnaire (QLQ)-C30 [ Time Frame: Baseline, Week 49 Day 1 (Day 337) ]
The EORTC QLQ-C30 core measurement was used to capture distal outcomes, including physical, social functioning, and overall health-related quality of life. The questionnaire incorporates 30 questions comprising nine multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social); 3 symptom scales (fatigue, pain, and nausea and vomiting); and a global health and quality of life scale. All raw domain scores are linearly transformed to a 0-100 scale. The global health and quality of life domain is presented. An increase in activity or functioning scores indicates improvement (higher/healthier level of functioning) and a decrease in symptom scores indicates improvement (lower level of symptoms/problems).
Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 [ Time Frame: Baseline, Week 49 Day 1 (Day 337) ]
The EORTC QLQ-C30 core measurement was used to capture distal outcomes, including physical, social functioning, and overall health-related quality of life. The questionnaire incorporates 30 questions comprising nine multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social); 3 symptom scales (fatigue, pain, and nausea and vomiting); and a global health and quality of life scale. All raw domain scores are linearly transformed to a 0-100 scale. All domains except for the global health and quality are presented. An increase in activity or functioning scores indicates improvement (higher/healthier level of functioning) and a decrease in symptom scores indicates improvement (lower level of symptoms/problems).
Change From Baseline In QoL Total Score As Assessed By The EORTC-QLQ-PR25 Sexual Activity And Functioning And Hormonal-Treatment-Related Symptom Subdomains [ Time Frame: Baseline, Week 49 Day 1 (Day 337) ]
Subscales for assessment of hormonal treatment-related symptoms (6 items) and sexual activity and function (6 items) from the EORTC-QLQ-PR25 25-item prostate cancer module of the EORTC are presented. Questions used 4 point scale (1 'Not at all' to 4 'Very much'). All raw domain scores are linearly transformed to a 0-100 scale. An increase in activity or functioning scores indicates improvement (higher/healthier level of functioning) and a decrease in symptom scores indicates improvement (lower level of symptoms/problems).
Change From Baseline In QoL Total Score For Urinary And Bowel Symptoms Domains As Assessed By The EORTC-QLQ-PR25 [ Time Frame: Baseline, Week 49 Day 1 (Day 337) ]
Subscale assessments of urinary symptoms (9 items) and bowel symptoms (4 items) from the EORTC-QLQ-PR25 25-item prostate cancer module of the EORTC are presented. Questions used 4 point scale (1 'Not at all' to 4 'Very much'). All raw domain scores are linearly transformed to a 0-100 scale. A decrease in symptom scores indicates improvement (lower level of symptoms/problems).
Change From Baseline In QoL Total Score As Assessed By The European Quality Of Life 5-Dimension 5-Level Questionnaire (EuroQoL EQ-5D-5L) [ Time Frame: Baseline, Week 49 Day 1 (Day 337) ]
The EuroQoL EQ-5D-5L comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 5 levels: no problems (1 as numerical score), slight problems (2 as numerical score), moderate problems (3 as numerical score), severe problems (4 as numerical score), and extreme problems (5 as numerical score). The total score ranges from 0 to 100. A decrease in score indicates improvement.
Percent Change From Baseline In Serum Concentrations Of Luteinizing Hormone [ Time Frame: Week 1 Day 4 (Day 4), Week 5 Day 1 (Day 29), Week 25 Day 1 (Day 169), and Week 49 Day 1 (Day 337) ]
Blood samples were collected from participants for hormonal measurements.
Percent Change From Baseline In Serum Concentrations Of FSH [ Time Frame: Week 1 Day 4 (Day 4), Week 5 Day 1 (Day 29), Week 25 Day 1 (Day 169), and Week 49 Day 1 (Day 337) ]
Blood samples were collected from participants for hormonal measurements.
Percent Change From Baseline In Serum Concentrations Of Dihydrotestosterone [ Time Frame: Week 5 Day 1 (Day 29), Week 25 Day 1 (Day 169), and Week 49 Day 1 (Day 337) ]
Blood samples were collected from participants for hormonal measurements.
Percent Change From Baseline In Serum Concentrations Of Sex Hormone-Binding Globulin [ Time Frame: Week 5 Day 1 (Day 29), Week 25 Day 1 (Day 169), and Week 49 Day 1 (Day 337) ]
Blood samples were collected from participants for hormonal measurements.
Maximum Observed Plasma Concentration (Cmax) Of Relugolix [ Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1 and Week 2 ]
The Cmax of relugolix was determined for single and repeat doses in subsets of participants from Japan. Single dose pharmacokinetics (PK) was assessed on Day 1 following an initial 360 mg dose of relugolix. Repeat dose PK was assessed following repeat dosing of relugolix 120 mg once daily for 2 weeks.
Area Under The Concentration-Time Curve (AUC0-τ) Of Relugolix [ Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1 and Week 2 ]
The AUC0-τ of relugolix was determined for single and repeat doses in subsets of participants from Japan. Single dose PK was assessed on Day 1 following an initial 360 mg dose of relugolix. Repeat dose PK was assessed following repeat dosing of relugolix 120 mg once daily for 2 weeks.
Time To Maximum Observed Plasma Concentration (Tmax) Of Relugolix [ Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1 and Week 2 ]
The Tmax of relugolix was determined for single and repeat doses in subsets of participants from Japan. Single dose PK was assessed on Day 1 following an initial 360 mg dose of relugolix. Repeat dose PK was assessed following repeat dosing of relugolix 120 mg once daily for 2 weeks.
Other Outcome Measures:
Percentage of Participants Who Experienced Major Adverse Cardiovascular Events (MACE) [ Time Frame: From Week 5 Day 1 (Day 29) to Week 49 Day 1 (Day 337) ]
MACE were defined as nonfatal myocardial infarction, nonfatal stroke, and death from any cause.
Inclution Criteria
Inclusion Criteria
All of the following inclusion criteria must have been met prior to randomization unless otherwise specified:
1. Has voluntarily signed and dated the informed consent form prior to initiation of any
screening or study-specific procedures;
2. Is a male aged 18 years or older on the day of signing and dating the informed consent form;
3. Has histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate;
4. Is a candidate for, in the opinion of the investigator, at least 1 year of continuous androgen
deprivation therapy for the management of androgen-sensitive advanced prostate cancer
with one of the following clinical disease state presentations:
a. Evidence of biochemical (PSA) or clinical relapse following local primary intervention
with curative intent, such as surgery, radiation therapy, cryotherapy, or high-frequency
ultrasound and not a candidate for salvage treatment by surgery (radiotherapy,
cryotherapy, or high frequency ultrasound are allowed after 2 months of androgen
deprivation therapy); or
b. Newly diagnosed androgen-sensitive metastatic disease; or
c. Advanced localized disease not suitable for local primary surgical intervention with
curative intent (radiotherapy, cryotherapy, or high frequency ultrasound are allowed
after 2 months of androgen deprivation therapy);
5. Has a serum testosterone at the Screening visit of ≥ 150 ng/dL (5.2 nmol/L);
6. Has a serum PSA concentration at the Screening visit of > 2.0 ng/mL (2.0 µg/L), or, when
applicable, post radical prostatectomy of > 0.2 ng/mL (0.2 µg/L) or post radiotherapy,
cryotherapy, or high frequency ultrasound > 2.0 ng/mL (2.0 µg/L) above the post interventional nadir;
7. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at initial
screening and at baseline (refer to Appendix 1);
8. Is a male patient who, even if surgically sterilized (ie, status post vasectomy):
a. Agrees to use a male condom if having sex with a woman of childbearing age or a
pregnant woman, during the entire study Treatment Period and through 4 months after
the last dose of study drug; or
b. Agrees to practice true abstinence, when this is in line with the preferred and usual
lifestyle of the patient. Periodic abstinence (eg, calendar, ovulation, symptothermal,
postovulation methods for the female partner) and withdrawal are not acceptable
methods of contraception;
9. Must agree not to donate sperm from first dose of study drug through 4 months after the last
dose of study drug;
10. A randomization authorization form has been signed by a study medical monitor approving
the patient for randomization into the trial.
All of the following inclusion criteria must have been met prior to randomization unless otherwise specified:
1. Has voluntarily signed and dated the informed consent form prior to initiation of any
screening or study-specific procedures;
2. Is a male aged 18 years or older on the day of signing and dating the informed consent form;
3. Has histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate;
4. Is a candidate for, in the opinion of the investigator, at least 1 year of continuous androgen
deprivation therapy for the management of androgen-sensitive advanced prostate cancer
with one of the following clinical disease state presentations:
a. Evidence of biochemical (PSA) or clinical relapse following local primary intervention
with curative intent, such as surgery, radiation therapy, cryotherapy, or high-frequency
ultrasound and not a candidate for salvage treatment by surgery (radiotherapy,
cryotherapy, or high frequency ultrasound are allowed after 2 months of androgen
deprivation therapy); or
b. Newly diagnosed androgen-sensitive metastatic disease; or
c. Advanced localized disease not suitable for local primary surgical intervention with
curative intent (radiotherapy, cryotherapy, or high frequency ultrasound are allowed
after 2 months of androgen deprivation therapy);
5. Has a serum testosterone at the Screening visit of ≥ 150 ng/dL (5.2 nmol/L);
6. Has a serum PSA concentration at the Screening visit of > 2.0 ng/mL (2.0 µg/L), or, when
applicable, post radical prostatectomy of > 0.2 ng/mL (0.2 µg/L) or post radiotherapy,
cryotherapy, or high frequency ultrasound > 2.0 ng/mL (2.0 µg/L) above the post interventional nadir;
7. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at initial
screening and at baseline (refer to Appendix 1);
8. Is a male patient who, even if surgically sterilized (ie, status post vasectomy):
a. Agrees to use a male condom if having sex with a woman of childbearing age or a
pregnant woman, during the entire study Treatment Period and through 4 months after
the last dose of study drug; or
b. Agrees to practice true abstinence, when this is in line with the preferred and usual
lifestyle of the patient. Periodic abstinence (eg, calendar, ovulation, symptothermal,
postovulation methods for the female partner) and withdrawal are not acceptable
methods of contraception;
9. Must agree not to donate sperm from first dose of study drug through 4 months after the last
dose of study drug;
10. A randomization authorization form has been signed by a study medical monitor approving
the patient for randomization into the trial.
Exclusion Criteria
Exclusion Criteria
A patient will not be eligible for inclusion in this study if any of the following criteria apply:
1. In the investigator’s opinion, is likely to require chemotherapy or surgical therapy for
symptomatic disease management within 2 months of initiating androgen deprivation therapy;
2. Previously received GnRH analog or other form of androgen deprivation therapy (estrogen
or antiandrogen) for > 12 months total duration. If androgen deprivation therapy was
received for ≤ 12 months total duration, then that therapy must have been completed at least
12 months prior to baseline;
3. Previous treatment for prostate cancer with a taxane-based regimen;
4. Metastases to brain per prior clinical evaluation;
5. Features of the patient’s medical condition that make life expectancy due to other medical
conditions of less than 5 years;
6. Scheduled for major surgery after baseline;
7. History of surgical castration;
8. Diagnosis of or treatment for another malignancy within the 2 years before baseline, or
presence of another malignancy with evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have
undergone complete resection. Patients with Stage 0 or Stage 1 melanoma or superficial
Stage 0 or Stage 1 bladder cancer, if curatively managed prior to screening, are not
excluded. The medical monitor should be contacted for any questions regarding this exclusion criterion;
9. Abnormal laboratory values at the Screening visit that suggest a clinically unstable
underlying disease, or the following laboratory values:
a. Serum gamma-glutamyl transferase > 2.0 x upper limit of normal (ULN);
b. Serum alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 1.0 x ULN;
c. Total bilirubin > 1.0 x ULN (unless secondary to Gilbert’s syndrome or the pattern is
consistent with a diagnosis of Gilbert’s syndrome) or;
d. Serum creatinine > 2.0 mg/dL;
10. Uncontrolled diabetes with hemoglobin A1c (HbA1c) > 10% or previously undiagnosed
diabetes mellitus with screening HbA1c > 8% (such excluded patients may be rescreened
after referral and evidence of improved control of their condition);
11. Has jaundice or known current active liver disease from any cause, including hepatitis A
(hepatitis A virus immunoglobulin M [IgM] positive), hepatitis B (hepatitis B virus surface
antigen [HBsAg] positive), or hepatitis C (hepatitis C virus [HCV] antibody positive,
confirmed by HCV ribonucleic acid);
12. Known human immunodeficiency virus infection;
13. Within 6 months before baseline, a history of myocardial infarction, angina, unstable
symptomatic ischemic heart disease, or congestive heart failure, or any history of clinically
significant ventricular arrhythmias such as ventricular tachycardia, ventricular fibrillation,
or torsades de pointes, or history of Mobitz II second degree or third degree heart block
without permanent pacemaker in place or untreated supraventricular tachycardia (heart rate
≥ 120 beats per minute); thromboembolic events (eg, deep vein thrombosis, pulmonary
embolism, or symptomatic cerebrovascular events); or any other significant cardiac
condition (eg, pericardial effusion, restrictive cardiomyopathy). Patients with chronic stable
atrial fibrillation on stable anticoagulant therapy or patients with stable cardiac rhythm
controlled by a pacemaker are allowed;
14. The following ECG abnormalities are excluded:
a. Q-wave infarction, unless identified 6 or more months before the Screening visit;
b. QT interval corrected for heart rate (QTc) > 470 msec. If the QTc is prolonged in a
patient with a pacemaker, the patient may be enrolled in the study upon discussion with
the medical monitor; or
c. Congenital long QT syndrome;
15. Uncontrolled hypertension despite appropriate medical therapy (sitting blood pressure of
greater than 160 mmHg systolic and/or 100 mmHg diastolic at 2 separate measurements no
more than 45 minutes apart during the Screening visit). Patients may be re-screened after
referral and further management of hypertension;
16. Hypotension, as indicated by systolic blood pressure < 84 mmHg on 2 repeat measures at
least 15 minutes apart, or treated ongoing symptomatic orthostatic hypotension with
> 20 mmHg decrease in systolic blood pressure one minute or more after assuming upright position;
17. Bradycardia as indicated by a heart rate of < 45 beats per minute on the ECG at the
Screening or Baseline Day 1 visit;
18. Treatment for prostate cancer with any investigational products within 12 months before the
first dose of study drug (approved products under investigation for an alternative condition,
not directly related to therapy for prostate cancer, may be allowed);
19. Treatment with an investigational product for indications other than prostate cancer within 3 months;
20. Previous treatment with relugolix in a clinical study;
21. Patient is a study site employee or is a primary family member (spouse, parent, child, or
sibling) of a site employee involved in the conduct of the study;
22. Known gastrointestinal disease or procedure that could interfere with the oral absorption or
tolerance of relugolix, including inability to swallow whole tablets;
23. Use of any medication listed in the prohibited medications table (see Section 5.10.1)
without the appropriate washout period;
24. Has a contraindication or history of sensitivity to any of the study treatments or components
thereof; or has a history of drug or other allergy that, in the opinion of the investigator or
medical monitor, contraindicates study participation;
25. Has a prior (within 1 year of the Screening visit) or current history of drug or alcohol abuse
disorder according to Diagnostic and Statistical Manual of Mental Disorders V (all patients
must be questioned about their drug and alcohol use and this should be documented in the
electronic case report form [eCRF]);
26. Any serious medical condition that limits life expectancy to less than 5 years, or any other
medical or psychiatric condition that, in opinion of investigator, would interfere with
completion of treatment according to this protocol.
A patient will not be eligible for inclusion in this study if any of the following criteria apply:
1. In the investigator’s opinion, is likely to require chemotherapy or surgical therapy for
symptomatic disease management within 2 months of initiating androgen deprivation therapy;
2. Previously received GnRH analog or other form of androgen deprivation therapy (estrogen
or antiandrogen) for > 12 months total duration. If androgen deprivation therapy was
received for ≤ 12 months total duration, then that therapy must have been completed at least
12 months prior to baseline;
3. Previous treatment for prostate cancer with a taxane-based regimen;
4. Metastases to brain per prior clinical evaluation;
5. Features of the patient’s medical condition that make life expectancy due to other medical
conditions of less than 5 years;
6. Scheduled for major surgery after baseline;
7. History of surgical castration;
8. Diagnosis of or treatment for another malignancy within the 2 years before baseline, or
presence of another malignancy with evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have
undergone complete resection. Patients with Stage 0 or Stage 1 melanoma or superficial
Stage 0 or Stage 1 bladder cancer, if curatively managed prior to screening, are not
excluded. The medical monitor should be contacted for any questions regarding this exclusion criterion;
9. Abnormal laboratory values at the Screening visit that suggest a clinically unstable
underlying disease, or the following laboratory values:
a. Serum gamma-glutamyl transferase > 2.0 x upper limit of normal (ULN);
b. Serum alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 1.0 x ULN;
c. Total bilirubin > 1.0 x ULN (unless secondary to Gilbert’s syndrome or the pattern is
consistent with a diagnosis of Gilbert’s syndrome) or;
d. Serum creatinine > 2.0 mg/dL;
10. Uncontrolled diabetes with hemoglobin A1c (HbA1c) > 10% or previously undiagnosed
diabetes mellitus with screening HbA1c > 8% (such excluded patients may be rescreened
after referral and evidence of improved control of their condition);
11. Has jaundice or known current active liver disease from any cause, including hepatitis A
(hepatitis A virus immunoglobulin M [IgM] positive), hepatitis B (hepatitis B virus surface
antigen [HBsAg] positive), or hepatitis C (hepatitis C virus [HCV] antibody positive,
confirmed by HCV ribonucleic acid);
12. Known human immunodeficiency virus infection;
13. Within 6 months before baseline, a history of myocardial infarction, angina, unstable
symptomatic ischemic heart disease, or congestive heart failure, or any history of clinically
significant ventricular arrhythmias such as ventricular tachycardia, ventricular fibrillation,
or torsades de pointes, or history of Mobitz II second degree or third degree heart block
without permanent pacemaker in place or untreated supraventricular tachycardia (heart rate
≥ 120 beats per minute); thromboembolic events (eg, deep vein thrombosis, pulmonary
embolism, or symptomatic cerebrovascular events); or any other significant cardiac
condition (eg, pericardial effusion, restrictive cardiomyopathy). Patients with chronic stable
atrial fibrillation on stable anticoagulant therapy or patients with stable cardiac rhythm
controlled by a pacemaker are allowed;
14. The following ECG abnormalities are excluded:
a. Q-wave infarction, unless identified 6 or more months before the Screening visit;
b. QT interval corrected for heart rate (QTc) > 470 msec. If the QTc is prolonged in a
patient with a pacemaker, the patient may be enrolled in the study upon discussion with
the medical monitor; or
c. Congenital long QT syndrome;
15. Uncontrolled hypertension despite appropriate medical therapy (sitting blood pressure of
greater than 160 mmHg systolic and/or 100 mmHg diastolic at 2 separate measurements no
more than 45 minutes apart during the Screening visit). Patients may be re-screened after
referral and further management of hypertension;
16. Hypotension, as indicated by systolic blood pressure < 84 mmHg on 2 repeat measures at
least 15 minutes apart, or treated ongoing symptomatic orthostatic hypotension with
> 20 mmHg decrease in systolic blood pressure one minute or more after assuming upright position;
17. Bradycardia as indicated by a heart rate of < 45 beats per minute on the ECG at the
Screening or Baseline Day 1 visit;
18. Treatment for prostate cancer with any investigational products within 12 months before the
first dose of study drug (approved products under investigation for an alternative condition,
not directly related to therapy for prostate cancer, may be allowed);
19. Treatment with an investigational product for indications other than prostate cancer within 3 months;
20. Previous treatment with relugolix in a clinical study;
21. Patient is a study site employee or is a primary family member (spouse, parent, child, or
sibling) of a site employee involved in the conduct of the study;
22. Known gastrointestinal disease or procedure that could interfere with the oral absorption or
tolerance of relugolix, including inability to swallow whole tablets;
23. Use of any medication listed in the prohibited medications table (see Section 5.10.1)
without the appropriate washout period;
24. Has a contraindication or history of sensitivity to any of the study treatments or components
thereof; or has a history of drug or other allergy that, in the opinion of the investigator or
medical monitor, contraindicates study participation;
25. Has a prior (within 1 year of the Screening visit) or current history of drug or alcohol abuse
disorder according to Diagnostic and Statistical Manual of Mental Disorders V (all patients
must be questioned about their drug and alcohol use and this should be documented in the
electronic case report form [eCRF]);
26. Any serious medical condition that limits life expectancy to less than 5 years, or any other
medical or psychiatric condition that, in opinion of investigator, would interfere with
completion of treatment according to this protocol.
The Estimated Number of Participants
-
Taiwan
40 participants
-
Global
1100 participants
