Prostate Cancer
Conditions
Brief summary
The purpose of this study is to determine the efficacy and safety of relugolix 120 milligrams (mg) orally once daily for 48 weeks on maintaining serum testosterone suppression to castrate levels (\< 50 nanograms/deciliter \[ng/dL\]) in participants with androgen-sensitive advanced prostate cancer.
Detailed description
This is a phase 3, multinational, randomized, open-label, parallel group study to evaluate the efficacy and safety of oral daily relugolix 120 mg in participants with androgen-sensitive advanced prostate cancer who require at least 1 year of continuous androgen-deprivation therapy. Relugolix 120 mg orally once daily or leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan based on local labels), every 3 months by subcutaneous injection will be administered to participants. There are 2 analyses for this study, a primary analysis and a final analysis. Primary Analysis: The primary analysis of efficacy and safety has been completed (N=934). Participants were randomized 2:1 to receive relugolix or leuprolide for 48 weeks, followed by a 30-day safety follow-up visit or early termination 30-day safety follow-up. Final Analysis: The final analysis will occur after additional participants with metastatic disease (approximately 130) have been enrolled and randomized from any sites to the study, and have completed the 48-week treatment period. A cohort of participants enrolled in China and Taiwan will be analyzed separately once they have completed treatment to support registration in China. Eligible participants were randomized 2:1 to relugolix or leuprolide arm and will attend visits monthly (every 4 weeks) where serum testosterone and prostate-specific antigen will be assessed. Safety will be assessed throughout the study by monitoring adverse events, vital signs, physical examinations, clinical laboratory tests, and 12-lead electrocardiograms. Castration resistance-free survival will be assessed up to Week 49, Day 1 of the study and reported as part of the final analysis. The study enrolled 1134 participants, including 139 participants with metastatic advanced prostate cancer to support the analysis of the secondary endpoint of castration resistance-free survival and 93 Chinese participants (enrolled in China and Taiwan) to support registration in China.
Interventions
DRUGRelugolix
Relugolix 120-mg tablet administered orally once daily following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1
DRUGLeuprolide Acetate
Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan, Taiwan, and China), every 3 months by subcutaneous injection
Sponsors
Myovant Sciences GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Has histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate. 2. 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 1 of the following clinical disease state presentations: 1. 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; or 2. Newly diagnosed androgen-sensitive metastatic disease; or 3. Advanced localized disease unlikely to be cured by local primary intervention with either surgery or radiation with curative intent. 3. Has a serum testosterone at the Screening visit of ≥ 150 ng/dL (5.2 nanomoles \[nmol\]/liter \[L\]). 4. Has a serum PSA concentration at the Screening visit of \> 2.0 ng/milliliter (mL) (2.0 microgram \[μg\]/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. 5. Has an Eastern Cooperative Oncology Group performance status of 0 or 1 at initial screening and at baseline. Key
Exclusion criteria
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 gonadotropin-releasing hormone analog or other form of androgen deprivation therapy (estrogen or antiandrogen) for \> 18 months total duration. If androgen deprivation therapy was received for ≤ 18 months total duration, then that therapy must have been completed at least 3 months prior to baseline. If the dosing interval of the depot is longer than 3 months, then the prior androgen deprivation therapy must have been completed at least as long as the dosing interval of the depot. 3. Previous systemic cytotoxic treatment for prostate cancer (for example, taxane-based regimen). 4. Metastases to brain per prior clinical evaluation. 5. Participants with myocardial infarction, unstable symptomatic ischemic heart disease, cerebrovascular events, or any significant cardiac condition within the prior 6 months. 6. Active conduction system abnormalities. 7. Uncontrolled hypertension.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sustained Castration Rate | 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
| Measure | Time frame | Description |
|---|---|---|
| Castration Rate At Week 1 Day 4 | 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 | 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 | 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) | 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 | 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 | 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 | 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 | 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 | 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) | 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 | 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 | 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. |
| 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 | 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 | 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 | 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 | 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) | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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. |
| Rate Of PSA Progression-free Survival | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experienced Major Adverse Cardiovascular Events (MACE) | 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. |
Countries
Australia, Austria, Belgium, Brazil, Canada, China, Denmark, Finland, France, Germany, Italy, Japan, Netherlands, New Zealand, Poland, Slovakia, South Korea, Spain, Sweden, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
To support registration in China, the study continued to enroll additional nonmetastatic or metastatic participants from China after the final analysis to reach the target enrollment of approximately 90 participants.
Pre-assignment details
The primary analysis of efficacy and safety included 934 participants. The primary analysis excluded additional participants with metastatic disease and a cohort of participants enrolled in China and Taiwan who will be included in the final analysis of the study (N=200).
Participants by arm
| Arm | Count |
|---|---|
| Relugolix Relugolix 120-mg tablet administered orally once daily for 48 weeks following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1. | 622 |
| Leuprolide Acetate Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan), every 3 months by subcutaneous injection. | 308 |
| Total | 930 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 23 | 8 |
| Overall Study | Did not Receive Study Drug | 2 | 2 |
| Overall Study | Dosing Interruption (Logistical Reason) | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Physician Decision | 9 | 3 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Testosterone Suppression Level Not Met | 7 | 13 |
| Overall Study | Withdrawal by Subject | 17 | 6 |
Baseline characteristics
| Characteristic | Leuprolide Acetate | Total | Relugolix |
|---|---|---|---|
| Age, Continuous | 71.0 years STANDARD_DEVIATION 8.03 | 71.1 years STANDARD_DEVIATION 7.84 | 71.2 years STANDARD_DEVIATION 7.75 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 31 Participants | 83 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 269 Participants | 827 Participants | 558 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 8 Participants | 20 Participants | 12 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 71 Participants | 198 Participants | 127 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 46 Participants | 30 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 15 Participants | 11 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 15 Participants | 35 Participants | 20 Participants |
| Race (NIH/OMB) White | 202 Participants | 636 Participants | 434 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 308 Participants | 930 Participants | 622 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 622 | 9 / 308 |
| other Total, other adverse events | 493 / 622 | 239 / 308 |
| serious Total, serious adverse events | 76 / 622 | 47 / 308 |
Outcome results
Primary
Sustained Castration Rate
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.
Time frame: From Week 5 Day 1 (Day 29) to Week 49 Day 1 (Day 337)
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relugolix | Sustained Castration Rate | 96.7 percentage of participants |
| Leuprolide Acetate | Sustained Castration Rate | 88.8 percentage of participants |
Comparison: Following statistical analysis of the lower bound of the 95% CI ≥ 90% for the relugolix group, secondary statistical analysis of non-inferiority was conducted.95% CI: [4.1, 11.8]
Comparison: Following statistical analysis of the lower bound of the 95% CI ≥ 90% for the relugolix group, secondary statistical analysis of superiority was conducted.p-value: <0.0001t-test, 2 sided
Secondary
Area Under The Concentration-Time Curve (AUC0-τ) Of Relugolix
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 frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1 and Week 2
Population: A subset of Japanese participants enrolled in study were included in the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Relugolix | Area Under The Concentration-Time Curve (AUC0-τ) Of Relugolix | 663 ng⸳hr/mL | Geometric Coefficient of Variation 151 |
| Leuprolide Acetate | Area Under The Concentration-Time Curve (AUC0-τ) Of Relugolix | 373 ng⸳hr/mL | Geometric Coefficient of Variation 51 |
Secondary
Castration Rate At Week 1 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.
Time frame: Week 1 Day 4 (Day 4)
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relugolix | Castration Rate At Week 1 Day 4 | 56.04 percentage of participants |
| Leuprolide Acetate | Castration Rate At Week 1 Day 4 | 0.00 percentage of participants |
Comparison: Alpha-protected statistical analysis.p-value: <0.0001t-test, 2 sided
Secondary
Castration Rate At Week 3 Day 1
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.
Time frame: Week 3 Day 1 (Day 15)
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relugolix | Castration Rate At Week 3 Day 1 | 98.71 percentage of participants |
| Leuprolide Acetate | Castration Rate At Week 3 Day 1 | 12.05 percentage of participants |
Comparison: Alpha-protected statistical analysis.p-value: <0.0001t-test, 2 sided
Secondary
Change From Baseline In QoL Total Score As Assessed By The EORTC-QLQ-PR25 Sexual Activity And Functioning And Hormonal-Treatment-Related Symptom Subdomains
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).
Time frame: Baseline, Week 49 Day 1 (Day 337)
Population: All randomized participants who received at least 1 dose of study drug and had analyzable data at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Relugolix | Change From Baseline In QoL Total Score As Assessed By The EORTC-QLQ-PR25 Sexual Activity And Functioning And Hormonal-Treatment-Related Symptom Subdomains | Sexual activity | 13.9 score on a scale | Standard Deviation 26.51 |
| Relugolix | Change From Baseline In QoL Total Score As Assessed By The EORTC-QLQ-PR25 Sexual Activity And Functioning And Hormonal-Treatment-Related Symptom Subdomains | Sexual functioning | -9.0 score on a scale | Standard Deviation 23.37 |
| Relugolix | Change From Baseline In QoL Total Score As Assessed By The EORTC-QLQ-PR25 Sexual Activity And Functioning And Hormonal-Treatment-Related Symptom Subdomains | Hormonal treatment-related symptoms | 10.6 score on a scale | Standard Deviation 12.25 |
| Leuprolide Acetate | Change From Baseline In QoL Total Score As Assessed By The EORTC-QLQ-PR25 Sexual Activity And Functioning And Hormonal-Treatment-Related Symptom Subdomains | Sexual activity | 10.8 score on a scale | Standard Deviation 27.9 |
| Leuprolide Acetate | Change From Baseline In QoL Total Score As Assessed By The EORTC-QLQ-PR25 Sexual Activity And Functioning And Hormonal-Treatment-Related Symptom Subdomains | Sexual functioning | -10.4 score on a scale | Standard Deviation 21.1 |
| Leuprolide Acetate | Change From Baseline In QoL Total Score As Assessed By The EORTC-QLQ-PR25 Sexual Activity And Functioning And Hormonal-Treatment-Related Symptom Subdomains | Hormonal treatment-related symptoms | 11.4 score on a scale | Standard Deviation 13.3 |
Secondary
Change From Baseline In QoL Total Score As Assessed By The European Quality Of Life 5-Dimension 5-Level Questionnaire (EuroQoL EQ-5D-5L)
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.
Time frame: Baseline, Week 49 Day 1 (Day 337)
Population: All randomized participants who received at least 1 dose of study drug and had analyzable data at the specified timepoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Relugolix | Change From Baseline In QoL Total Score As Assessed By The European Quality Of Life 5-Dimension 5-Level Questionnaire (EuroQoL EQ-5D-5L) | -1.5 score on a scale | Standard Deviation 14.36 |
| Leuprolide Acetate | Change From Baseline In QoL Total Score As Assessed By The European Quality Of Life 5-Dimension 5-Level Questionnaire (EuroQoL EQ-5D-5L) | -2.7 score on a scale | Standard Deviation 14.57 |
Secondary
Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30
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).
Time frame: Baseline, Week 49 Day 1 (Day 337)
Population: All randomized participants who received at least 1 dose of study drug and had analyzable data at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Relugolix | Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 | Physical functioning | -4.6 score on a scale | Standard Deviation 13.09 |
| Relugolix | Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 | Role functioning | -6.2 score on a scale | Standard Deviation 19.92 |
| Relugolix | Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 | Emotional functioning | 0.5 score on a scale | Standard Deviation 16.12 |
| Relugolix | Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 | Cognitive functioning | -3.7 score on a scale | Standard Deviation 16.77 |
| Relugolix | Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 | Social functioning | -2.7 score on a scale | Standard Deviation 18.31 |
| Relugolix | Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 | Fatigue | 6.1 score on a scale | Standard Deviation 19.46 |
| Relugolix | Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 | Nausea and vomiting | 0.2 score on a scale | Standard Deviation 7.12 |
| Relugolix | Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 | Pain | 1.7 score on a scale | Standard Deviation 20.19 |
| Relugolix | Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 | Dyspnoea | 5.3 score on a scale | Standard Deviation 19.16 |
| Relugolix | Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 | Insomnia | 4.8 score on a scale | Standard Deviation 25.88 |
| Relugolix | Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 | Appetite loss | -0.6 score on a scale | Standard Deviation 17.82 |
| Relugolix | Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 | Constipation | 1.4 score on a scale | Standard Deviation 23.26 |
| Relugolix | Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 | Diarrhoea | 2.0 score on a scale | Standard Deviation 16.7 |
| Relugolix | Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 | Financial difficulties | 0.2 score on a scale | Standard Deviation 18.28 |
| Leuprolide Acetate | Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 | Appetite loss | -0.6 score on a scale | Standard Deviation 14.86 |
| Leuprolide Acetate | Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 | Physical functioning | -4.4 score on a scale | Standard Deviation 12.29 |
| Leuprolide Acetate | Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 | Pain | 4.0 score on a scale | Standard Deviation 21.96 |
| Leuprolide Acetate | Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 | Role functioning | -5.6 score on a scale | Standard Deviation 17.84 |
| Leuprolide Acetate | Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 | Diarrhoea | 1.4 score on a scale | Standard Deviation 19.6 |
| Leuprolide Acetate | Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 | Emotional functioning | -0.5 score on a scale | Standard Deviation 13.23 |
| Leuprolide Acetate | Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 | Dyspnoea | 7.9 score on a scale | Standard Deviation 20.25 |
| Leuprolide Acetate | Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 | Cognitive functioning | -3.8 score on a scale | Standard Deviation 16.37 |
| Leuprolide Acetate | Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 | Constipation | 3.5 score on a scale | Standard Deviation 18.88 |
| Leuprolide Acetate | Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 | Social functioning | -4.0 score on a scale | Standard Deviation 18.18 |
| Leuprolide Acetate | Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 | Insomnia | 4.8 score on a scale | Standard Deviation 21.82 |
| Leuprolide Acetate | Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 | Fatigue | 7.0 score on a scale | Standard Deviation 18.4 |
| Leuprolide Acetate | Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 | Financial difficulties | 0.1 score on a scale | Standard Deviation 19.21 |
| Leuprolide Acetate | Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 | Nausea and vomiting | 0.8 score on a scale | Standard Deviation 6.02 |
Secondary
Change From Baseline In QoL Total Score For Urinary And Bowel Symptoms Domains As Assessed By The EORTC-QLQ-PR25
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).
Time frame: Baseline, Week 49 Day 1 (Day 337)
Population: All randomized participants who received at least 1 dose of study drug and had analyzable data at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Relugolix | Change From Baseline In QoL Total Score For Urinary And Bowel Symptoms Domains As Assessed By The EORTC-QLQ-PR25 | Urinary symptoms | 1.1 score on a scale | Standard Deviation 15.29 |
| Relugolix | Change From Baseline In QoL Total Score For Urinary And Bowel Symptoms Domains As Assessed By The EORTC-QLQ-PR25 | Incontinence aid use | 1.0 score on a scale | Standard Deviation 15.41 |
| Relugolix | Change From Baseline In QoL Total Score For Urinary And Bowel Symptoms Domains As Assessed By The EORTC-QLQ-PR25 | Bowel symptoms | 1.2 score on a scale | Standard Deviation 8.92 |
| Leuprolide Acetate | Change From Baseline In QoL Total Score For Urinary And Bowel Symptoms Domains As Assessed By The EORTC-QLQ-PR25 | Urinary symptoms | -0.4 score on a scale | Standard Deviation 13.78 |
| Leuprolide Acetate | Change From Baseline In QoL Total Score For Urinary And Bowel Symptoms Domains As Assessed By The EORTC-QLQ-PR25 | Incontinence aid use | 0.0 score on a scale | Standard Deviation 19.8 |
| Leuprolide Acetate | Change From Baseline In QoL Total Score For Urinary And Bowel Symptoms Domains As Assessed By The EORTC-QLQ-PR25 | Bowel symptoms | 2.0 score on a scale | Standard Deviation 9.51 |
Secondary
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
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).
Time frame: Baseline, Week 49 Day 1 (Day 337)
Population: All randomized participants who received at least 1 dose of study drug and had analyzable data at the specified timepoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Relugolix | 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 | -3.8 score on a scale | Standard Deviation 18.13 |
| Leuprolide Acetate | 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 | -3.6 score on a scale | Standard Deviation 15.7 |
Secondary
Confirmed Prostate-specific Antigen (PSA) Response Rate
Confirmed PSA response defined as \> 50% reduction in PSA from baseline at Week 3 Day 1 followed with confirmation at Week 5 Day 1.
Time frame: Week 3 Day 1 (Day 15) and Week 5 Day 1 (Day 29)
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relugolix | Confirmed Prostate-specific Antigen (PSA) Response Rate | 79.4 percentage of participants |
| Leuprolide Acetate | Confirmed Prostate-specific Antigen (PSA) Response Rate | 19.8 percentage of participants |
Comparison: Alpha-protected statistical analysis.p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Follicle-stimulating Hormone (FSH) Level
To evaluate the effect of relugolix and leuprolide acetate on FSH suppression.
Time frame: Week 25 Day 1 (Day 169)
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Relugolix | Follicle-stimulating Hormone (FSH) Level | 1.72 IU/L | Standard Deviation 1.376 |
| Leuprolide Acetate | Follicle-stimulating Hormone (FSH) Level | 5.95 IU/L | Standard Deviation 3.071 |
Comparison: Alpha-protected statistical analysis.p-value: <0.0001t-test, 2 sided
Secondary
Maximum Observed Plasma Concentration (Cmax) Of Relugolix
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.
Time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1 and Week 2
Population: A subset of Japanese participants enrolled in study were included in the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Relugolix | Maximum Observed Plasma Concentration (Cmax) Of Relugolix | 125 ng/mL | Geometric Coefficient of Variation 220 |
| Leuprolide Acetate | Maximum Observed Plasma Concentration (Cmax) Of Relugolix | 46.4 ng/mL | Geometric Coefficient of Variation 141 |
Secondary
Percent Change From Baseline In Serum Concentrations Of Dihydrotestosterone
Blood samples were collected from participants for hormonal measurements.
Time frame: Week 5 Day 1 (Day 29), Week 25 Day 1 (Day 169), and Week 49 Day 1 (Day 337)
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Relugolix | Percent Change From Baseline In Serum Concentrations Of Dihydrotestosterone | Week 5 Day 1 (Day 29) | -87.61 percent change | Standard Deviation 12.225 |
| Relugolix | Percent Change From Baseline In Serum Concentrations Of Dihydrotestosterone | Week 25 Day 1 (Day 169) | -88.06 percent change | Standard Deviation 11.81 |
| Relugolix | Percent Change From Baseline In Serum Concentrations Of Dihydrotestosterone | Week 49 Day 1 (Day 337) | -88.23 percent change | Standard Deviation 11.235 |
| Leuprolide Acetate | Percent Change From Baseline In Serum Concentrations Of Dihydrotestosterone | Week 5 Day 1 (Day 29) | -81.95 percent change | Standard Deviation 23.733 |
| Leuprolide Acetate | Percent Change From Baseline In Serum Concentrations Of Dihydrotestosterone | Week 25 Day 1 (Day 169) | -85.45 percent change | Standard Deviation 32.261 |
| Leuprolide Acetate | Percent Change From Baseline In Serum Concentrations Of Dihydrotestosterone | Week 49 Day 1 (Day 337) | -87.56 percent change | Standard Deviation 12.088 |
Secondary
Percent Change From Baseline In Serum Concentrations Of FSH
Blood samples were collected from participants for hormonal measurements.
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)
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Relugolix | Percent Change From Baseline In Serum Concentrations Of FSH | Week 1 Day 4 (Day 4) | -62.59 percent change | Standard Deviation 9.051 |
| Relugolix | Percent Change From Baseline In Serum Concentrations Of FSH | Week 5 Day 1 (Day 29) | -90.80 percent change | Standard Deviation 8.151 |
| Relugolix | Percent Change From Baseline In Serum Concentrations Of FSH | Week 25 Day 1 (Day 169) | -86.32 percent change | Standard Deviation 10.699 |
| Relugolix | Percent Change From Baseline In Serum Concentrations Of FSH | Week 49 Day 1 (Day 337) | -79.39 percent change | Standard Deviation 21.987 |
| Leuprolide Acetate | Percent Change From Baseline In Serum Concentrations Of FSH | Week 49 Day 1 (Day 337) | -47.23 percent change | Standard Deviation 30.112 |
| Leuprolide Acetate | Percent Change From Baseline In Serum Concentrations Of FSH | Week 1 Day 4 (Day 4) | -4.74 percent change | Standard Deviation 36.121 |
| Leuprolide Acetate | Percent Change From Baseline In Serum Concentrations Of FSH | Week 25 Day 1 (Day 169) | -47.53 percent change | Standard Deviation 32.56 |
| Leuprolide Acetate | Percent Change From Baseline In Serum Concentrations Of FSH | Week 5 Day 1 (Day 29) | -67.73 percent change | Standard Deviation 27.311 |
Secondary
Percent Change From Baseline In Serum Concentrations Of Luteinizing Hormone
Blood samples were collected from participants for hormonal measurements.
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)
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Relugolix | Percent Change From Baseline In Serum Concentrations Of Luteinizing Hormone | Week 1 Day 4 (Day 4) | -88.25 Percent change | Standard Deviation 20.696 |
| Relugolix | Percent Change From Baseline In Serum Concentrations Of Luteinizing Hormone | Week 5 Day 1 (Day 29) | -94.54 Percent change | Standard Deviation 8.5 |
| Relugolix | Percent Change From Baseline In Serum Concentrations Of Luteinizing Hormone | Week 25 Day 1 (Day 169) | -93.93 Percent change | Standard Deviation 7.242 |
| Relugolix | Percent Change From Baseline In Serum Concentrations Of Luteinizing Hormone | Week 49 Day 1 (Day 337) | -91.54 Percent change | Standard Deviation 16.779 |
| Leuprolide Acetate | Percent Change From Baseline In Serum Concentrations Of Luteinizing Hormone | Week 49 Day 1 (Day 337) | -95.14 Percent change | Standard Deviation 4.507 |
| Leuprolide Acetate | Percent Change From Baseline In Serum Concentrations Of Luteinizing Hormone | Week 1 Day 4 (Day 4) | 147.71 Percent change | Standard Deviation 122.735 |
| Leuprolide Acetate | Percent Change From Baseline In Serum Concentrations Of Luteinizing Hormone | Week 25 Day 1 (Day 169) | -93.45 Percent change | Standard Deviation 13.202 |
| Leuprolide Acetate | Percent Change From Baseline In Serum Concentrations Of Luteinizing Hormone | Week 5 Day 1 (Day 29) | -82.67 Percent change | Standard Deviation 27.146 |
Secondary
Percent Change From Baseline In Serum Concentrations Of Sex Hormone-Binding Globulin
Blood samples were collected from participants for hormonal measurements.
Time frame: Week 5 Day 1 (Day 29), Week 25 Day 1 (Day 169), and Week 49 Day 1 (Day 337)
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Relugolix | Percent Change From Baseline In Serum Concentrations Of Sex Hormone-Binding Globulin | Week 5 Day 1 (Day 29) | 1.08 percent change | Standard Deviation 22.068 |
| Relugolix | Percent Change From Baseline In Serum Concentrations Of Sex Hormone-Binding Globulin | Week 25 Day 1 (Day 169) | 7.24 percent change | Standard Deviation 28.265 |
| Relugolix | Percent Change From Baseline In Serum Concentrations Of Sex Hormone-Binding Globulin | Week 49 Day 1 (Day 337) | 6.54 percent change | Standard Deviation 28.787 |
| Leuprolide Acetate | Percent Change From Baseline In Serum Concentrations Of Sex Hormone-Binding Globulin | Week 5 Day 1 (Day 29) | -1.21 percent change | Standard Deviation 20.43 |
| Leuprolide Acetate | Percent Change From Baseline In Serum Concentrations Of Sex Hormone-Binding Globulin | Week 25 Day 1 (Day 169) | 3.59 percent change | Standard Deviation 24.947 |
| Leuprolide Acetate | Percent Change From Baseline In Serum Concentrations Of Sex Hormone-Binding Globulin | Week 49 Day 1 (Day 337) | 2.59 percent change | Standard Deviation 27.051 |
Secondary
Profound Castration Rate 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.
Time frame: At Week 1 Day 4 (Day 4)
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relugolix | Profound Castration Rate At Week 1 Day 4 (Day 4) | 6.92 percentage of participants |
| Leuprolide Acetate | Profound Castration Rate At Week 1 Day 4 (Day 4) | 0.0 percentage of participants |
Secondary
Profound Castration Rate At 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.
Time frame: Week 3 Day 1 (Day 15)
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relugolix | Profound Castration Rate At Week 3 Day 1 (Day 15) | 78.38 percentage of participants |
| Leuprolide Acetate | Profound Castration Rate At Week 3 Day 1 (Day 15) | 0.98 percentage of participants |
Comparison: Alpha-protected statistical analysis.p-value: <0.000195% CI: [73.98, 80.83]t-test, 2 sided
Secondary
PSA Response Rate At Week 3 Day 1
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.
Time frame: Week 3 Day 1 (Day 15)
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relugolix | PSA Response Rate At Week 3 Day 1 | 80.1 percentage of participants |
| Leuprolide Acetate | PSA Response Rate At Week 3 Day 1 | 20.1 percentage of participants |
Secondary
PSA Response Rate At Week 5 Day 1
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.
Time frame: Week 5 Day 1 (Day 29)
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relugolix | PSA Response Rate At Week 5 Day 1 | 94.5 percentage of participants |
| Leuprolide Acetate | PSA Response Rate At Week 5 Day 1 | 79.2 percentage of participants |
Secondary
Rate Of PSA Progression-free Survival
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.
Time frame: Week 49 Day 1 (Day 337)
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relugolix | Rate Of PSA Progression-free Survival | 89.31 percentage of participants |
| Leuprolide Acetate | Rate Of PSA Progression-free Survival | 89.50 percentage of participants |
Secondary
Sustained Profound Castration Rate From Week 25 Day 1 Through Week 49 Day 1
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.
Time frame: Week 25 Day 1 (Day 169) through Week 49 Day 1 (Day 337)
Population: All randomized participants who received at least 1 dose of study drug and had analyzable data at the specified timepoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relugolix | Sustained Profound Castration Rate From Week 25 Day 1 Through Week 49 Day 1 | 84.6 percentage of participants |
| Leuprolide Acetate | Sustained Profound Castration Rate From Week 25 Day 1 Through Week 49 Day 1 | 87.5 percentage of participants |
95% CI: [-7.8, 2]
Secondary
Sustained Profound Castration Rate From Week 5 Day 1 Through Week 49 Day 1
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.
Time frame: Week 5 Day 1 (Day 29) through Week 49 Day 1 (Day 337)
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relugolix | Sustained Profound Castration Rate From Week 5 Day 1 Through Week 49 Day 1 | 81.6 percentage of participants |
| Leuprolide Acetate | Sustained Profound Castration Rate From Week 5 Day 1 Through Week 49 Day 1 | 68.6 percentage of participants |
95% CI: [6.9, 19.1]
Secondary
Testosterone Recovery Rate
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.
Time frame: Day 90 follow-up
Population: All randomized participants who received at least 1 dose of study drug and were followed in the testosterone recovery phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Relugolix | Testosterone Recovery Rate | ≥ 50 ng/dL | 93.01 percentage of participants |
| Relugolix | Testosterone Recovery Rate | > 280 ng/dL | 53.93 percentage of participants |
| Relugolix | Testosterone Recovery Rate | > Baseline level or 280 ng/dL | 54.73 percentage of participants |
| Leuprolide Acetate | Testosterone Recovery Rate | ≥ 50 ng/dL | 10.12 percentage of participants |
| Leuprolide Acetate | Testosterone Recovery Rate | > 280 ng/dL | 3.23 percentage of participants |
| Leuprolide Acetate | Testosterone Recovery Rate | > Baseline level or 280 ng/dL | 3.23 percentage of participants |
Secondary
Time To Maximum Observed Plasma Concentration (Tmax) Of Relugolix
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.
Time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1 and Week 2
Population: A subset of Japanese participants enrolled in study were included in the PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Relugolix | Time To Maximum Observed Plasma Concentration (Tmax) Of Relugolix | 1.03 hours |
| Leuprolide Acetate | Time To Maximum Observed Plasma Concentration (Tmax) Of Relugolix | 0.983 hours |
Secondary
Undetectable PSA Rate
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.
Time frame: Week 25 Day 1 (Day 169)
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relugolix | Undetectable PSA Rate | 20.7 percentage of participants |
| Leuprolide Acetate | Undetectable PSA Rate | 20.8 percentage of participants |
Other Pre-specified
Percentage of Participants Who Experienced Major Adverse Cardiovascular Events (MACE)
MACE were defined as nonfatal myocardial infarction, nonfatal stroke, and death from any cause.
Time frame: From Week 5 Day 1 (Day 29) to Week 49 Day 1 (Day 337)
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relugolix | Percentage of Participants Who Experienced Major Adverse Cardiovascular Events (MACE) | 2.9 percentage of participants |
| Leuprolide Acetate | Percentage of Participants Who Experienced Major Adverse Cardiovascular Events (MACE) | 6.2 percentage of participants |