Trial Outcomes & Findings for A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease (NCT NCT02663908)

Last Updated: 2022-06-29

Results Overview

Composite MACE endpoint was defined as: death due to any cause, non-fatal myocardial infarction or non-fatal stroke. Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict first confirmed (adjudicated) occurrence of composite MACE over time. Percentage of observed subjects with outcome measure events during the trial are reported. Subjects were censored at the time a subject discontinued the trial, was lost to follow-up, discontinued treatment with IMP, initiated treatment with prohibited medication (including hormonal combination therapy), or at Day 336, whichever occurred first.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

545 participants

Primary outcome timeframe

Randomization to Day 336 (end-of-trial)

Results posted on

2022-06-29

Participant Flow

The trial was performed at 113 investigational sites in 12 countries between Apr 2016 to Mar 2021.

In total, 702 subjects were screened of which 545 subjects were randomized. Of the randomized subjects, 544 subjects were exposed to the investigational medicinal product (IMP): 275 to Degarelix and 269 to Leuprolide. One subject was randomized in error and not exposed to IMP.

Participant milestones

Participant milestones
Measure	Degarelix 240 mg/80 mg Degarelix 240 mg/80 mg: Degarelix at a starting dose of 240 mg administered as two subcutaneous (SC) depot injections, each containing 120 mg of degarelix; followed by up to 11 maintenance doses of 80 mg degarelix administered as single SC depot injections at monthly (28-day) intervals.	Leuprolide 22.5 mg Leuprolide 22.5 mg: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Overall Study STARTED	276	269
Overall Study Full Analysis Set (FAS)	275	269
Overall Study COMPLETED	244	245
Overall Study NOT COMPLETED	32	24

Reasons for withdrawal

Reasons for withdrawal
Measure	Degarelix 240 mg/80 mg Degarelix 240 mg/80 mg: Degarelix at a starting dose of 240 mg administered as two subcutaneous (SC) depot injections, each containing 120 mg of degarelix; followed by up to 11 maintenance doses of 80 mg degarelix administered as single SC depot injections at monthly (28-day) intervals.	Leuprolide 22.5 mg Leuprolide 22.5 mg: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Overall Study Withdrawal by Subject	8	5
Overall Study Lost to Follow-up	1	5
Overall Study Adverse Event	13	11
Overall Study Protocol Violation	1	2
Overall Study Lack of therapeutic response	2	0
Overall Study COVID-19	1	0
Overall Study Site closed	1	0
Overall Study Subject to begin treatment with an exclusionary medication	1	0
Overall Study Subject ended trial due to being prescribed prohibited medication	1	0
Overall Study Intolerance to FIRMAGON therapy	1	0
Overall Study Death	1	0
Overall Study Subject randomized in error and did not receive the IMP	1	0
Overall Study Subject discontinued treatment as he was in hospice and could not make it for end-of-trial visit	0	1

Baseline Characteristics

Number analyzed differs from the overall population as baseline ethnicity was not reported for some of the subjects.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Degarelix 240 mg/80 mg n=275 Participants Degarelix 240 mg/80 mg: Degarelix at a starting dose of 240 mg administered as two SC depot injections, each containing 120 mg of degarelix; followed by up to 11 maintenance doses of 80 mg degarelix administered as single SC depot injections at monthly (28-day) intervals.	Leuprolide 22.5 mg n=269 Participants Leuprolide 22.5 mg: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.	Total n=544 Participants Total of all reporting groups
Age, Continuous	73.3 years STANDARD_DEVIATION 7.28 • n=275 Participants	73.1 years STANDARD_DEVIATION 7.16 • n=269 Participants	73.2 years STANDARD_DEVIATION 7.22 • n=544 Participants
Age, Customized < 75 years	153 Participants n=275 Participants	151 Participants n=269 Participants	304 Participants n=544 Participants
Age, Customized >= 75 years	122 Participants n=275 Participants	118 Participants n=269 Participants	240 Participants n=544 Participants
Sex: Female, Male Female	0 Participants n=275 Participants	0 Participants n=269 Participants	0 Participants n=544 Participants
Sex: Female, Male Male	275 Participants n=275 Participants	269 Participants n=269 Participants	544 Participants n=544 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	16 Participants n=275 Participants • Number analyzed differs from the overall population as baseline ethnicity was not reported for some of the subjects.	14 Participants n=269 Participants • Number analyzed differs from the overall population as baseline ethnicity was not reported for some of the subjects.	30 Participants n=544 Participants • Number analyzed differs from the overall population as baseline ethnicity was not reported for some of the subjects.
Ethnicity (NIH/OMB) Not Hispanic or Latino	256 Participants n=275 Participants • Number analyzed differs from the overall population as baseline ethnicity was not reported for some of the subjects.	254 Participants n=269 Participants • Number analyzed differs from the overall population as baseline ethnicity was not reported for some of the subjects.	510 Participants n=544 Participants • Number analyzed differs from the overall population as baseline ethnicity was not reported for some of the subjects.
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=275 Participants • Number analyzed differs from the overall population as baseline ethnicity was not reported for some of the subjects.	1 Participants n=269 Participants • Number analyzed differs from the overall population as baseline ethnicity was not reported for some of the subjects.	4 Participants n=544 Participants • Number analyzed differs from the overall population as baseline ethnicity was not reported for some of the subjects.
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=275 Participants • Number analyzed differs from the overall population as baseline race was not reported for some of the subjects.	0 Participants n=269 Participants • Number analyzed differs from the overall population as baseline race was not reported for some of the subjects.	2 Participants n=544 Participants • Number analyzed differs from the overall population as baseline race was not reported for some of the subjects.
Race (NIH/OMB) Asian	3 Participants n=275 Participants • Number analyzed differs from the overall population as baseline race was not reported for some of the subjects.	5 Participants n=269 Participants • Number analyzed differs from the overall population as baseline race was not reported for some of the subjects.	8 Participants n=544 Participants • Number analyzed differs from the overall population as baseline race was not reported for some of the subjects.
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=275 Participants • Number analyzed differs from the overall population as baseline race was not reported for some of the subjects.	0 Participants n=269 Participants • Number analyzed differs from the overall population as baseline race was not reported for some of the subjects.	0 Participants n=544 Participants • Number analyzed differs from the overall population as baseline race was not reported for some of the subjects.
Race (NIH/OMB) Black or African American	16 Participants n=275 Participants • Number analyzed differs from the overall population as baseline race was not reported for some of the subjects.	12 Participants n=269 Participants • Number analyzed differs from the overall population as baseline race was not reported for some of the subjects.	28 Participants n=544 Participants • Number analyzed differs from the overall population as baseline race was not reported for some of the subjects.
Race (NIH/OMB) White	252 Participants n=275 Participants • Number analyzed differs from the overall population as baseline race was not reported for some of the subjects.	251 Participants n=269 Participants • Number analyzed differs from the overall population as baseline race was not reported for some of the subjects.	503 Participants n=544 Participants • Number analyzed differs from the overall population as baseline race was not reported for some of the subjects.
Race (NIH/OMB) More than one race	0 Participants n=275 Participants • Number analyzed differs from the overall population as baseline race was not reported for some of the subjects.	0 Participants n=269 Participants • Number analyzed differs from the overall population as baseline race was not reported for some of the subjects.	0 Participants n=544 Participants • Number analyzed differs from the overall population as baseline race was not reported for some of the subjects.
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=275 Participants • Number analyzed differs from the overall population as baseline race was not reported for some of the subjects.	1 Participants n=269 Participants • Number analyzed differs from the overall population as baseline race was not reported for some of the subjects.	3 Participants n=544 Participants • Number analyzed differs from the overall population as baseline race was not reported for some of the subjects.
Region of Enrollment Greece	15 participants n=275 Participants	15 participants n=269 Participants	30 participants n=544 Participants
Region of Enrollment Canada	25 participants n=275 Participants	25 participants n=269 Participants	50 participants n=544 Participants
Region of Enrollment United States	111 participants n=275 Participants	102 participants n=269 Participants	213 participants n=544 Participants
Region of Enrollment Czechia	22 participants n=275 Participants	25 participants n=269 Participants	47 participants n=544 Participants
Region of Enrollment Finland	0 participants n=275 Participants	1 participants n=269 Participants	1 participants n=544 Participants
Region of Enrollment Poland	3 participants n=275 Participants	5 participants n=269 Participants	8 participants n=544 Participants
Region of Enrollment South Africa	2 participants n=275 Participants	0 participants n=269 Participants	2 participants n=544 Participants
Region of Enrollment United Kingdom	8 participants n=275 Participants	7 participants n=269 Participants	15 participants n=544 Participants
Region of Enrollment Slovakia	37 participants n=275 Participants	45 participants n=269 Participants	82 participants n=544 Participants
Region of Enrollment France	16 participants n=275 Participants	14 participants n=269 Participants	30 participants n=544 Participants
Region of Enrollment Germany	10 participants n=275 Participants	9 participants n=269 Participants	19 participants n=544 Participants
Region of Enrollment Russia	26 participants n=275 Participants	21 participants n=269 Participants	47 participants n=544 Participants
Baseline body mass index (BMI)	28.38 kg/m^2 STANDARD_DEVIATION 5.057 • n=273 Participants • Number analyzed differs from the overall population as baseline BMI was not reported for some of the subjects.	28.58 kg/m^2 STANDARD_DEVIATION 4.589 • n=268 Participants • Number analyzed differs from the overall population as baseline BMI was not reported for some of the subjects.	28.48 kg/m^2 STANDARD_DEVIATION 4.828 • n=541 Participants • Number analyzed differs from the overall population as baseline BMI was not reported for some of the subjects.
Stage of prostate cancer Localized	138 Participants n=275 Participants	133 Participants n=269 Participants	271 Participants n=544 Participants
Stage of prostate cancer Locally Advanced	63 Participants n=275 Participants	80 Participants n=269 Participants	143 Participants n=544 Participants
Stage of prostate cancer Metastatic	63 Participants n=275 Participants	48 Participants n=269 Participants	111 Participants n=544 Participants
Stage of prostate cancer Not classifiable	11 Participants n=275 Participants	8 Participants n=269 Participants	19 Participants n=544 Participants
Eastern Cooperative Oncology Group (ECOG) performance score 0 score	178 Participants n=275 Participants	167 Participants n=269 Participants	345 Participants n=544 Participants
Eastern Cooperative Oncology Group (ECOG) performance score 1 score	75 Participants n=275 Participants	80 Participants n=269 Participants	155 Participants n=544 Participants
Eastern Cooperative Oncology Group (ECOG) performance score 2 score	8 Participants n=275 Participants	11 Participants n=269 Participants	19 Participants n=544 Participants
Testosterone levels	353.6 ng/dL STANDARD_DEVIATION 150.49 • n=274 Participants • Number analyzed differs from the overall population as baseline testosterone was not reported for some of the subjects.	351.6 ng/dL STANDARD_DEVIATION 140.32 • n=269 Participants • Number analyzed differs from the overall population as baseline testosterone was not reported for some of the subjects.	352.6 ng/dL STANDARD_DEVIATION 145.41 • n=543 Participants • Number analyzed differs from the overall population as baseline testosterone was not reported for some of the subjects.
Prostate Specific Antigen (PSA)	119.7 ng/mL STANDARD_DEVIATION 472.10 • n=275 Participants • Number analyzed differs from the overall population as baseline PSA was not reported for some of the subjects.	59.9 ng/mL STANDARD_DEVIATION 236.68 • n=268 Participants • Number analyzed differs from the overall population as baseline PSA was not reported for some of the subjects.	90.2 ng/mL STANDARD_DEVIATION 375.72 • n=543 Participants • Number analyzed differs from the overall population as baseline PSA was not reported for some of the subjects.

PRIMARY outcome

Timeframe: Randomization to Day 336 (end-of-trial)

Population: The FAS consisted of all randomized and treated subjects (who received at least one dose of IMP) and was analyzed based on the planned (randomized) treatment.

Outcome measures

Outcome measures
Measure	Degarelix 240 mg/80 mg n=275 Participants Degarelix 240 mg/80 mg: Degarelix at a starting dose of 240 mg administered as two SC depot injections, each containing 120 mg of degarelix; followed by up to 11 maintenance doses of 80 mg degarelix administered as single SC depot injections at monthly (28-day) intervals.	Leuprolide 22.5 mg n=269 Participants Leuprolide 22.5 mg: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Time From Randomization to the First Confirmed (Adjudicated) Occurrence of the Composite Major Adverse Cardiovascular Event (MACE) Endpoint; Percentage of Observed Subjects With Outcome Measure Events During the Trial	5.5 percentage of subjects	4.1 percentage of subjects

SECONDARY outcome

Timeframe: Randomization to Day 336 (end-of-trial)

Population: The FAS consisted of all randomized and treated subjects (who received at least one dose of IMP) and was analyzed based on the planned (randomized) treatment.

Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict confirmed (adjudicated) occurrence of CV-related death, non-fatal myocardial infarction or non-fatal stroke. Percentage of observed subjects with outcome measure events during the trial are reported. Subjects were censored at the time a subject discontinued the trial, was lost to follow-up, discontinued treatment with IMP, initiated treatment with prohibited medication (including hormonal combination therapy), or at Day 336, whichever occurred first.

Outcome measures

Outcome measures
Measure	Degarelix 240 mg/80 mg n=275 Participants Degarelix 240 mg/80 mg: Degarelix at a starting dose of 240 mg administered as two SC depot injections, each containing 120 mg of degarelix; followed by up to 11 maintenance doses of 80 mg degarelix administered as single SC depot injections at monthly (28-day) intervals.	Leuprolide 22.5 mg n=269 Participants Leuprolide 22.5 mg: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Time From Randomization to the First Confirmed (Adjudicated) Occurrence of Cardiovascular (CV)-Related Death, Non-fatal Myocardial Infarction or Non-fatal Stroke; Percentage of Observed Subjects With Outcome Measure Events During the Trial	3.3 percentage of subjects	2.6 percentage of subjects

SECONDARY outcome

Timeframe: Randomization to Day 336 (end-of-trial)

Population: The FAS consisted of all randomized and treated subjects (who received at least one dose of IMP) and was analyzed based on the planned (randomized) treatment.

Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict confirmed (adjudicated) CV-related death. Percentage of observed subjects with outcome measure events during the trial are reported. Percentage of observed subjects with outcome measure events during the trial are reported. Subjects were censored at the time a subject discontinued the trial, was lost to follow-up, discontinued treatment with IMP, initiated treatment with prohibited medication (including hormonal combination therapy), or at Day 336, whichever occurred first.

Outcome measures

Outcome measures
Measure	Degarelix 240 mg/80 mg n=275 Participants Degarelix 240 mg/80 mg: Degarelix at a starting dose of 240 mg administered as two SC depot injections, each containing 120 mg of degarelix; followed by up to 11 maintenance doses of 80 mg degarelix administered as single SC depot injections at monthly (28-day) intervals.	Leuprolide 22.5 mg n=269 Participants Leuprolide 22.5 mg: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Time From Randomization to Confirmed (Adjudicated) CV-related Death; Percentage of Observed Subjects With Outcome Measure Events During the Trial	0.4 percentage of subjects	1.9 percentage of subjects

SECONDARY outcome

Timeframe: Randomization to Day 336 (end-of-trial)

Population: The FAS consisted of all randomized and treated subjects (who received at least one dose of IMP) and was analyzed based on the planned (randomized) treatment.

Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict first confirmed (adjudicated) myocardial infarction. Percentage of observed subjects with outcome measure events during the trial are reported. Subjects were censored at the time a subject discontinued the trial, was lost to follow-up, discontinued treatment with IMP, initiated treatment with prohibited medication (including hormonal combination therapy), or at Day 336, whichever occurred first.

Outcome measures

Outcome measures
Measure	Degarelix 240 mg/80 mg n=275 Participants Degarelix 240 mg/80 mg: Degarelix at a starting dose of 240 mg administered as two SC depot injections, each containing 120 mg of degarelix; followed by up to 11 maintenance doses of 80 mg degarelix administered as single SC depot injections at monthly (28-day) intervals.	Leuprolide 22.5 mg n=269 Participants Leuprolide 22.5 mg: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Time From Randomization to the First Confirmed (Adjudicated) Myocardial Infarction; Percentage of Observed Subjects With Outcome Measure Events During the Trial	1.8 percentage of subjects	1.1 percentage of subjects

SECONDARY outcome

Timeframe: Randomization to Day 336 (end-of-trial)

Population: The FAS consisted of all randomized and treated subjects (who received at least one dose of IMP) and was analyzed based on the planned (randomized) treatment.

Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict first confirmed (adjudicated) stroke. Percentage of observed subjects with outcome measure events during the trial are reported. Subjects were censored at the time a subject discontinued the trial, was lost to follow-up, discontinued treatment with IMP, initiated treatment with prohibited medication (including hormonal combination therapy), or at Day 336, whichever occurred first.

Outcome measures

Outcome measures
Measure	Degarelix 240 mg/80 mg n=275 Participants Degarelix 240 mg/80 mg: Degarelix at a starting dose of 240 mg administered as two SC depot injections, each containing 120 mg of degarelix; followed by up to 11 maintenance doses of 80 mg degarelix administered as single SC depot injections at monthly (28-day) intervals.	Leuprolide 22.5 mg n=269 Participants Leuprolide 22.5 mg: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Time From Randomization to the First Confirmed (Adjudicated) Stroke; Percentage of Observed Subjects With Outcome Measure Events During the Trial	1.1 percentage of subjects	1.1 percentage of subjects

SECONDARY outcome

Timeframe: Randomization to Day 336 (end-of-trial)

Population: The FAS consisted of all randomized and treated subjects (who received at least one dose of IMP) and was analyzed based on the planned (randomized) treatment.

Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict first confirmed (adjudicated) unstable angina requiring hospitalization. Percentage of observed subjects with outcome measure events during the trial are reported. Subjects were censored at the time a subject discontinued the trial, was lost to follow-up, discontinued treatment with IMP, initiated treatment with prohibited medication (including hormonal combination therapy), or at Day 336, whichever occurred first.

Outcome measures

Outcome measures
Measure	Degarelix 240 mg/80 mg n=275 Participants Degarelix 240 mg/80 mg: Degarelix at a starting dose of 240 mg administered as two SC depot injections, each containing 120 mg of degarelix; followed by up to 11 maintenance doses of 80 mg degarelix administered as single SC depot injections at monthly (28-day) intervals.	Leuprolide 22.5 mg n=269 Participants Leuprolide 22.5 mg: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Time From Randomization to the First Confirmed (Adjudicated) Unstable Angina Requiring Hospitalization; Percentage of Observed Subjects With Outcome Measure Events During the Trial	0.7 percentage of subjects	1.5 percentage of subjects

SECONDARY outcome

Timeframe: Randomization to Day 336 (end-of-trial)

Population: The FAS consisted of all randomized and treated subjects (who received at least one dose of IMP) and was analyzed based on the planned (randomized) treatment.

Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict death due to any cause. Percentage of observed subjects with outcome measure events during the trial are reported. Subjects were censored at the time a subject discontinued the trial, was lost to follow-up, discontinued treatment with IMP, initiated treatment with prohibited medication (including hormonal combination therapy), or at Day 336, whichever occurred first.

Outcome measures

Outcome measures
Measure	Degarelix 240 mg/80 mg n=275 Participants Degarelix 240 mg/80 mg: Degarelix at a starting dose of 240 mg administered as two SC depot injections, each containing 120 mg of degarelix; followed by up to 11 maintenance doses of 80 mg degarelix administered as single SC depot injections at monthly (28-day) intervals.	Leuprolide 22.5 mg n=269 Participants Leuprolide 22.5 mg: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Time From Randomization to Death Due to Any Cause; Percentage of Observed Subjects With Outcome Measure Events During the Trial	2.9 percentage of subjects	3.3 percentage of subjects

SECONDARY outcome

Timeframe: Days 28, 168 and 336 (end-of-trial)

Population: The FAS consisted of all randomized and treated subjects (who received at least one dose of IMP) and was analyzed based on the planned (randomized) treatment. Subjects analyzed for this endpoint represent subjects who were evaluable for this outcome measure.

Median levels and interquartile ranges for serum testosterone at Days 28, 168, and 336 are presented.

Outcome measures

Outcome measures
Measure	Degarelix 240 mg/80 mg n=264 Participants Degarelix 240 mg/80 mg: Degarelix at a starting dose of 240 mg administered as two SC depot injections, each containing 120 mg of degarelix; followed by up to 11 maintenance doses of 80 mg degarelix administered as single SC depot injections at monthly (28-day) intervals.	Leuprolide 22.5 mg n=257 Participants Leuprolide 22.5 mg: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Testosterone Levels at Days 28, 168 and 336 in the Degarelix and Leuprolide Treatment Groups Day 336	9.855 ng/dL Interval 5.76 to 14.41	8.650 ng/dL Interval 5.76 to 11.53
Testosterone Levels at Days 28, 168 and 336 in the Degarelix and Leuprolide Treatment Groups Day 28	8.650 ng/dL Interval 6.81 to 13.96	14.410 ng/dL Interval 10.91 to 20.17
Testosterone Levels at Days 28, 168 and 336 in the Degarelix and Leuprolide Treatment Groups Day 168	8.650 ng/dL Interval 5.76 to 12.75	8.475 ng/dL Interval 5.76 to 11.53

SECONDARY outcome

Timeframe: From randomization to end-of-trial for each subject (subjects not censored at Day 336)

Population: The FAS consisted of all randomized and treated subjects (who received at least one dose of IMP) and was analyzed based on the planned (randomized) treatment.

Time to failure in PFS was defined as the time, measured in days, from randomization to the first occurrence of either death, radiographic disease progression, introduction of additional prostate cancer therapies for progression, or PSA failure. Subjects who discontinued treatment with IMP or withdrew from the trial were censored at the time of discontinuation/withdrawal. Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict failure in PFS. Percentage of observed subjects with outcome measure events during the trial are reported.

Outcome measures

Outcome measures
Measure	Degarelix 240 mg/80 mg n=275 Participants Degarelix 240 mg/80 mg: Degarelix at a starting dose of 240 mg administered as two SC depot injections, each containing 120 mg of degarelix; followed by up to 11 maintenance doses of 80 mg degarelix administered as single SC depot injections at monthly (28-day) intervals.	Leuprolide 22.5 mg n=269 Participants Leuprolide 22.5 mg: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Time From Randomization to Failure in Progression-free Survival (PFS); Percentage of Observed Subjects With Outcome Measure Events During the Trial	8.7 percentage of subjects	10.0 percentage of subjects

SECONDARY outcome

Timeframe: Baseline to Days 168 and 336 (end-of-trial)

Lower urinary tract symptoms were measured with the IPSS Version 1 (IPSS-1). The IPSS is a subject-administered questionnaire containing seven items to evaluate symptoms of urinary obstruction (incomplete emptying, frequency, intermittency, urgency, weak stream, straining, nocturia) over the preceding week. Each urinary symptom question was assigned points from 0 to 5 indicating increasing severity of the particular symptom. The total IPSS-1 score was then calculated as summation over the responses for all 7 questions. The total IPSS-1 score was transformed to a scale from 0 (lowest score) to 100 (highest score). Higher scores reflect higher severity of symptoms. The IPSS-1 included an additional single question to assess a subject's QoL in relation to his urinary symptoms; response to this question was analyzed separately and was not included in the total IPSS score. The score was similarly scaled from 0 to 100. Change from baseline in IPSS Total and QoL scores are presented.

Outcome measures

Outcome measures
Measure	Degarelix 240 mg/80 mg n=234 Participants Degarelix 240 mg/80 mg: Degarelix at a starting dose of 240 mg administered as two SC depot injections, each containing 120 mg of degarelix; followed by up to 11 maintenance doses of 80 mg degarelix administered as single SC depot injections at monthly (28-day) intervals.	Leuprolide 22.5 mg n=232 Participants Leuprolide 22.5 mg: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Changes From Baseline in International Prostate Symptom Score (IPSS) Total and Quality of Life (QoL) Scores IPSS Total at Day 168	-0.000 score on a scale Interval -0.804 to 0.804	0.907 score on a scale Interval 0.098 to 1.715
Changes From Baseline in International Prostate Symptom Score (IPSS) Total and Quality of Life (QoL) Scores IPSS, QoL at Day 168	-0.115 score on a scale Interval -0.298 to 0.068	0.098 score on a scale Interval -0.086 to 0.282
Changes From Baseline in International Prostate Symptom Score (IPSS) Total and Quality of Life (QoL) Scores IPSS Total at Day 336	-0.795 score on a scale Interval -1.619 to 0.029	0.121 score on a scale Interval -0.712 to 0.953
Changes From Baseline in International Prostate Symptom Score (IPSS) Total and Quality of Life (QoL) Scores IPSS, QoL at Day 336	-0.281 score on a scale Interval -0.467 to -0.095	-0.234 score on a scale Interval -0.422 to -0.046

SECONDARY outcome

Timeframe: First dose of IMP to Day 336 (end-of-trial)

The total number of CV-related hospitalizations over the duration of the trial was defined as the number of hospitalizations due to CV-related adverse events, observed from the first exposure to IMP up until Day 336 for each subject.

Outcome measures

Outcome measures
Measure	Degarelix 240 mg/80 mg n=275 Participants Degarelix 240 mg/80 mg: Degarelix at a starting dose of 240 mg administered as two SC depot injections, each containing 120 mg of degarelix; followed by up to 11 maintenance doses of 80 mg degarelix administered as single SC depot injections at monthly (28-day) intervals.	Leuprolide 22.5 mg n=269 Participants Leuprolide 22.5 mg: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Total Number of CV-related Hospitalization Events Over the Duration of the Trial	15 Events	17 Events

SECONDARY outcome

Timeframe: First dose of IMP to Day 336 (end-of-trial)

The total number of CABG or PCI procedures observed for each subject over the duration of the trial

Outcome measures

Outcome measures
Measure	Degarelix 240 mg/80 mg n=275 Participants Degarelix 240 mg/80 mg: Degarelix at a starting dose of 240 mg administered as two SC depot injections, each containing 120 mg of degarelix; followed by up to 11 maintenance doses of 80 mg degarelix administered as single SC depot injections at monthly (28-day) intervals.	Leuprolide 22.5 mg n=269 Participants Leuprolide 22.5 mg: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Total Number of Coronary Artery By-pass Grafting (CABG) or Percutaneous Coronary Intervention (PCI) Procedures Over the Duration of the Trial	3 Events	6 Events

SECONDARY outcome

Timeframe: First dose of IMP to Day 336 (end-of-trial)

CV-related ER visit events (that did not lead to hospitalization) was observed from the first exposure to IMP up until Day 336 for each subject.

Outcome measures

Outcome measures
Measure	Degarelix 240 mg/80 mg n=275 Participants Degarelix 240 mg/80 mg: Degarelix at a starting dose of 240 mg administered as two SC depot injections, each containing 120 mg of degarelix; followed by up to 11 maintenance doses of 80 mg degarelix administered as single SC depot injections at monthly (28-day) intervals.	Leuprolide 22.5 mg n=269 Participants Leuprolide 22.5 mg: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Total Number of CV-related Emergency Room (ER) Visit Events Over the Duration of the Trial	8 Events	2 Events

SECONDARY outcome

Timeframe: Baseline to Day 336 (end-of-trial)

The EQ-5D-5L essentially consists of 2 systems - the EQ-5D-5L descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ VAS is an overall estimation of the present health status. The results from the EQ-5D-5L questionnaire were converted into quality adjusted life year (QALY) units. The QALY is estimated by combining the value of life (utility value) and length of life. Quality adjusted life years are based on a principle assuming that a year of life lived in perfect health is worth 1 QALY and that a year of life lived in a state of less than perfect health is worth less than 1.

Outcome measures

Outcome measures
Measure	Degarelix 240 mg/80 mg n=243 Participants Degarelix 240 mg/80 mg: Degarelix at a starting dose of 240 mg administered as two SC depot injections, each containing 120 mg of degarelix; followed by up to 11 maintenance doses of 80 mg degarelix administered as single SC depot injections at monthly (28-day) intervals.	Leuprolide 22.5 mg n=239 Participants Leuprolide 22.5 mg: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Change in Utility, Based on EuroQol Group 5 Dimensions 5 Levels Questionnaire (EQ-5D-5L)	0.794 QALY Interval 0.77 to 0.818	0.796 QALY Interval 0.772 to 0.82

SECONDARY outcome

Timeframe: Baseline to Days 168 and 336 (end-of-trial)

The DASI is a self-administered instrument developed to measure functional capacity in subjects with cardiovascular disease (CVD). It contains 12 items referring to the present time, assessing the ability to perform physical tasks in five domains: personal care (1 item), ambulation (4 items), household tasks (4 items), sexual function (1 item) and recreation (2 items). Each question was answered by one of four options: 'yes with no difficulty' / 'yes, but with some difficulty' / 'no, I can't do this' / 'don't do this for other reasons'. A global score was calculated with a higher score indicating a higher functional capacity. The minimum score is 0 and the maximum score is 58.2 points. Change from baseline in DASI Global score is presented.

Outcome measures

Outcome measures
Measure	Degarelix 240 mg/80 mg n=234 Participants Degarelix 240 mg/80 mg: Degarelix at a starting dose of 240 mg administered as two SC depot injections, each containing 120 mg of degarelix; followed by up to 11 maintenance doses of 80 mg degarelix administered as single SC depot injections at monthly (28-day) intervals.	Leuprolide 22.5 mg n=232 Participants Leuprolide 22.5 mg: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Changes From Baseline in Duke Activity Status Index (DASI) Global Score Change in DASI to Day 168	-2.65 score on a scale Interval -3.95 to -1.35	-1.08 score on a scale Interval -2.38 to 0.23
Changes From Baseline in Duke Activity Status Index (DASI) Global Score Change in DASI to Day 336	-2.18 score on a scale Interval -3.54 to -0.81	-3.01 score on a scale Interval -4.39 to -1.63

SECONDARY outcome

Timeframe: Baseline to Days 168 and 336 (end-of-trial)

The CAQ is a self-administered questionnaire developed to measure heart-focused anxiety in persons with or without heart disease. It contains 18 items referring to the present time assessing cardiac anxiety in three domains: fear (8 items, each item could be scored between 0 "never" to 4 "always", maximum total score 32), avoidance (5 items, each item could be scored between 0 "never" to 4 "always", maximum total score 20) and attention (5 items, each item could be scored between 0 "never" to 4 "always", maximum total score 20). A higher score indicated greater cardiac anxiety and the total score range was between 0 and 72. Change from baseline in CAQ Global score and score per domain are presented.

Outcome measures

Outcome measures
Measure	Degarelix 240 mg/80 mg n=234 Participants Degarelix 240 mg/80 mg: Degarelix at a starting dose of 240 mg administered as two SC depot injections, each containing 120 mg of degarelix; followed by up to 11 maintenance doses of 80 mg degarelix administered as single SC depot injections at monthly (28-day) intervals.	Leuprolide 22.5 mg n=232 Participants Leuprolide 22.5 mg: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Changes From Baseline in Cardiac Anxiety Questionnaire (CAQ) Global Score and Score Per Domain CAQ global score (Day 168)	0.034 score on a scale Interval -0.021 to 0.088	-0.011 score on a scale Interval -0.066 to 0.044
Changes From Baseline in Cardiac Anxiety Questionnaire (CAQ) Global Score and Score Per Domain CAQ domain score for Attention (Day 168)	0.030 score on a scale Interval -0.034 to 0.094	-0.006 score on a scale Interval -0.07 to 0.059
Changes From Baseline in Cardiac Anxiety Questionnaire (CAQ) Global Score and Score Per Domain CAQ domain score for Avoidance (Day 168)	0.155 score on a scale Interval 0.062 to 0.248	0.039 score on a scale Interval -0.054 to 0.133
Changes From Baseline in Cardiac Anxiety Questionnaire (CAQ) Global Score and Score Per Domain CAQ domain score for Fear (Day 168)	-0.036 score on a scale Interval -0.106 to 0.034	-0.048 score on a scale Interval -0.119 to 0.022
Changes From Baseline in Cardiac Anxiety Questionnaire (CAQ) Global Score and Score Per Domain CAQ global score (Day 336)	0.102 score on a scale Interval 0.043 to 0.161	0.051 score on a scale Interval -0.009 to 0.11
Changes From Baseline in Cardiac Anxiety Questionnaire (CAQ) Global Score and Score Per Domain CAQ domain score for Attention (Day 336)	0.023 score on a scale Interval -0.046 to 0.092	-0.015 score on a scale Interval -0.085 to 0.054
Changes From Baseline in Cardiac Anxiety Questionnaire (CAQ) Global Score and Score Per Domain CAQ domain score for Avoidance (Day 336)	0.228 score on a scale Interval 0.13 to 0.325	0.220 score on a scale Interval 0.122 to 0.319
Changes From Baseline in Cardiac Anxiety Questionnaire (CAQ) Global Score and Score Per Domain CAQ domain score for Fear (Day 336)	0.075 score on a scale Interval -0.003 to 0.153	-0.018 score on a scale Interval -0.097 to 0.061

SECONDARY outcome

Timeframe: Start of IMP treatment until 3 months after last dosing of IMP

Population: The safety analysis set consisted of all treated subjects (who received at least one dose of IMP) and was analyzed based on the actual treatment received.

Adverse events were recorded from signed informed consent until end-of-trial. Adverse events with onset after start of IMP treatment, and within 3 months after (1 month=28 days) last dosing of IMP, were considered 'treatment-emergent' and are presented for the safety analysis set.

Outcome measures

Outcome measures
Measure	Degarelix 240 mg/80 mg n=275 Participants Degarelix 240 mg/80 mg: Degarelix at a starting dose of 240 mg administered as two SC depot injections, each containing 120 mg of degarelix; followed by up to 11 maintenance doses of 80 mg degarelix administered as single SC depot injections at monthly (28-day) intervals.	Leuprolide 22.5 mg n=269 Participants Leuprolide 22.5 mg: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Number of Subjects With Adverse Events (AEs) AEs	250 subjects	228 subjects
Number of Subjects With Adverse Events (AEs) SAEs	47 subjects	44 subjects
Number of Subjects With Adverse Events (AEs) AE leading to death	11 subjects	9 subjects

SECONDARY outcome

Timeframe: Start of IMP treatment until 3 months after last dosing of IMP

Population: The safety analysis set consisted of all treated subjects (who received at least one dose of IMP) and was analyzed based on the actual treatment received.

The intensity of AE was graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (version 4.02) 5-point scale. AE were categorized as grade 1 Mild (minor; no specific medical intervention; asymptomatic laboratory findings only; marginal clinical relevance), Grade 2 Moderate (minimal intervention: local intervention; non-invasive intervention), Grade 3 Severe (significant symptoms, requiring hospitalization or invasive intervention; transfusion; elective interventional radiological procedure; therapeutic endoscopy or operation), Grade 4 Life-threatening or disabling (complicated by acute, life-threatening metabolic or CV complications such as circulatory failure, hemorrhage, sepsis. Life-threatening physiologic consequences; need for intensive care or emergent invasive procedure; emergent interventional radiological procedure, therapeutic endoscopy or operation) and Grade 5 Death. Events with grades 3, 4 and 5 were categorized as severe.

Outcome measures

Outcome measures
Measure	Degarelix 240 mg/80 mg n=275 Participants Degarelix 240 mg/80 mg: Degarelix at a starting dose of 240 mg administered as two SC depot injections, each containing 120 mg of degarelix; followed by up to 11 maintenance doses of 80 mg degarelix administered as single SC depot injections at monthly (28-day) intervals.	Leuprolide 22.5 mg n=269 Participants Leuprolide 22.5 mg: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Intensity of AEs Mild AE	224 subjects	200 subjects
Intensity of AEs Moderate AE	160 subjects	135 subjects
Intensity of AEs Severe AE	59 subjects	55 subjects

SECONDARY outcome

Timeframe: Baseline to Day 336 (end-of-trial)

Population: The safety analysis set consisted of all treated subjects (who received at least one dose of IMP) and was analyzed based on the actual treatment received. Subjects analyzed for this endpoint represent subjects who were evaluable for this outcome measure.

Number of subjects shifting from normal value(s) in vital signs (pulse and blood pressure) at baseline to clinically significant abnormal value(s) at end-of-trial are presented. Note: Only subjects with appropriate baseline and post-baseline data are included in the evaluation.

Outcome measures

Outcome measures
Measure	Degarelix 240 mg/80 mg n=196 Participants Degarelix 240 mg/80 mg: Degarelix at a starting dose of 240 mg administered as two SC depot injections, each containing 120 mg of degarelix; followed by up to 11 maintenance doses of 80 mg degarelix administered as single SC depot injections at monthly (28-day) intervals.	Leuprolide 22.5 mg n=193 Participants Leuprolide 22.5 mg: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Changes in Vital Signs	0 Participants	1 Participants

Adverse Events

Degarelix 240 mg/80 mg

Serious events: 47 serious events

Other events: 250 other events

Deaths: 11 deaths

Leuprolide 22.5 mg

Serious events: 44 serious events

Other events: 228 other events

Deaths: 9 deaths

Serious adverse events

Other adverse events

Additional Information

Global Clinical Compliance

Ferring Pharmaceuticals

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A Publications Committee, including the signatory investigators, other Steering Committee members, and Sponsor representatives was established to function as an independent body of scientific and medical experts acting to facilitate, encourage, and coordinate the complete and accurate presentation and publication of the trial results. Members of the Publication Committee are responsible for review and approval of all abstracts and manuscripts based on the trial results.
Publication restrictions are in place

Restriction type: OTHER