PRONOUNCE: A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease

Sponsor

Ferring Pharmaceuticals (Industry)

Overall Status

Terminated

CT.gov ID

NCT02663908

Collaborator

Memorial Sloan Kettering Cancer Center (Other), Duke Clinical Research Institute (Other)

545

Enrollment

133

Locations

Arms

59.3

Actual Duration (Months)

4.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this trial is to test if a marketed drug for advanced prostate cancer (FIRMAGON) can reduce the risk of cardiovascular complications as compared to another marketed drug for advanced prostate cancer (LUPRON DEPOT) in subjects with prostate cancer and cardiovascular disease.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Degarelix Drug: Leuprolide	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

545 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Multi-Center, Randomized, Assessor-Blind, Controlled Trial Comparing the Occurrence of Major Adverse Cardiovascular Events (MACEs) in Patients With Prostate Cancer and Cardiovascular Disease Receiving Degarelix (Gonadotropin-Releasing Hormone (GnRH) Receptor Antagonist) or Leuprolide (GnRH Receptor Agonist)

Actual Study Start Date :

Apr 19, 2016

Actual Primary Completion Date :

Mar 29, 2021

Actual Study Completion Date :

Mar 29, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Degarelix	Drug: Degarelix Other Names: FIRMAGON
Active Comparator: Leuprolide	Drug: Leuprolide Other Names: LUPRON DEPOT

Arm

Intervention/Treatment

Experimental: Degarelix

Drug: Degarelix

Other Names:

FIRMAGON

Active Comparator: Leuprolide

Drug: Leuprolide

Other Names:

LUPRON DEPOT

Outcome Measures

Primary Outcome Measures

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 [Randomization to Day 336 (end-of-trial)]
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.

Secondary Outcome Measures

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 [Randomization to Day 336 (end-of-trial)]
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.
Time From Randomization to Confirmed (Adjudicated) CV-related Death; Percentage of Observed Subjects With Outcome Measure Events During the Trial [Randomization to Day 336 (end-of-trial)]
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.
Time From Randomization to the First Confirmed (Adjudicated) Myocardial Infarction; Percentage of Observed Subjects With Outcome Measure Events During the Trial [Randomization to Day 336 (end-of-trial)]
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.
Time From Randomization to the First Confirmed (Adjudicated) Stroke; Percentage of Observed Subjects With Outcome Measure Events During the Trial [Randomization to Day 336 (end-of-trial)]
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.
Time From Randomization to the First Confirmed (Adjudicated) Unstable Angina Requiring Hospitalization; Percentage of Observed Subjects With Outcome Measure Events During the Trial [Randomization to Day 336 (end-of-trial)]
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.
Time From Randomization to Death Due to Any Cause; Percentage of Observed Subjects With Outcome Measure Events During the Trial [Randomization to Day 336 (end-of-trial)]
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.
Testosterone Levels at Days 28, 168 and 336 in the Degarelix and Leuprolide Treatment Groups [Days 28, 168 and 336 (end-of-trial)]
Median levels and interquartile ranges for serum testosterone at Days 28, 168, and 336 are presented.
Time From Randomization to Failure in Progression-free Survival (PFS); Percentage of Observed Subjects With Outcome Measure Events During the Trial [From randomization to end-of-trial for each subject (subjects not censored at Day 336)]
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.
Changes From Baseline in International Prostate Symptom Score (IPSS) Total and Quality of Life (QoL) Scores [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.
Total Number of CV-related Hospitalization Events Over the Duration of the Trial [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.
Total Number of Coronary Artery By-pass Grafting (CABG) or Percutaneous Coronary Intervention (PCI) Procedures Over the Duration of the Trial [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
Total Number of CV-related Emergency Room (ER) Visit Events Over the Duration of the Trial [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.
Change in Utility, Based on EuroQol Group 5 Dimensions 5 Levels Questionnaire (EQ-5D-5L) [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.
Changes From Baseline in Duke Activity Status Index (DASI) Global Score [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.
Changes From Baseline in Cardiac Anxiety Questionnaire (CAQ) Global Score and Score Per Domain [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.
Number of Subjects With Adverse Events (AEs) [Start of IMP treatment until 3 months after last dosing of IMP]
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.
Intensity of AEs [Start of IMP treatment until 3 months after last dosing of IMP]
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.
Changes in Vital Signs [Baseline to Day 336 (end-of-trial)]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

Advanced prostate cancer
Indication to initiate androgen deprivation therapy (ADT)
Predefined cardiovascular disease

Exclusion Criteria:

Previous or current hormonal management of prostate cancer (unless terminated at least 12 months prior to trial)
Acute cardiovascular disease in the previous 30 days

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Urology Center of Alabama PC	Birmingham	Alabama	United States	35209
2	Arizona Institute of Urology	Tucson	Arizona	United States	85704
3	Urological Associates of Southern Arizona	Tucson	Arizona	United States	85715
4	University of Arizona College of Medicine	Tucson	Arizona	United States	85724
5	Urology Associates, PA	Little Rock	Arkansas	United States	72211
6	Pacific Cancer Medical Center, Inc.	Anaheim	California	United States	92801
7	San Diego Clinical Trials	La Mesa	California	United States	91942
8	Clinical Trials Research	Lincoln	California	United States	95648
9	VA Greater Los Angeles Healthcare System	Los Angeles	California	United States	90073
10	University of California, Irvine Medical Center	Orange	California	United States	92868
11	Skyline Urology	Torrance	California	United States	90505
12	Innovative Clinical Research Institute	Whittier	California	United States	90603
13	Urology Center of Colorado	Denver	Colorado	United States	80211
14	Yale University	New Haven	Connecticut	United States	06519
15	Urologic Surgeons of Washington	Washington	District of Columbia	United States	20036
16	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida	United States	33140
17	San Marcus Research Clinic Inc	Miami	Florida	United States	33014
18	Clinical Research Center of Florida	Pompano Beach	Florida	United States	33060
19	Florida Urology Partners	Tampa	Florida	United States	33615
20	Comprehensive Urologic Care	Lake Barrington	Illinois	United States	60010
21	Springfield Clinic LLP	Springfield	Illinois	United States	62703
22	Urology of Indiana LLC	Greenwood	Indiana	United States	46032
23	First Urology PSC	Jeffersonville	Indiana	United States	47130
24	Iowa Clinic	West Des Moines	Iowa	United States	50266
25	University of Kansas Medical Center Research Institute, Inc.	Kansas City	Kansas	United States	66160
26	Kansas City Urology Care	Lenexa	Kansas	United States	66214
27	Regional Urology, LLC	Shreveport	Louisiana	United States	71106
28	Chesapeake Urology Associates, P.A.	Towson	Maryland	United States	21204
29	Delaware Valley Urology LLC Westhampton	Mount Laurel	New Jersey	United States	08054
30	Holy Name Medical Center	Teaneck	New Jersey	United States	07666
31	Urology Group of New Mexico PC	Albuquerque	New Mexico	United States	87109
32	Montefiore Medical Center PRIME	Bronx	New York	United States	10461
33	Advanced Urology Centers of New York Elmont Division	Elmont	New York	United States	11003
34	SUNY Upstate Medical University	Syracuse	New York	United States	13210
35	Duke University Medical Center	Durham	North Carolina	United States	27710
36	Veterans Affairs Medical Center-Salisbury, NC	Salisbury	North Carolina	United States	28144
37	Signal Point Clinical Research Center	Dayton	Ohio	United States	45409
38	Clinical Research Solutions PC	Middleburg Heights	Ohio	United States	44130
39	Urologic Consultants of Southeaster PA LLP	Bala-Cynwyd	Pennsylvania	United States	19004
40	Lancaster Urology	Lancaster	Pennsylvania	United States	17604
41	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
42	Ralph H. Johnson VA Medical Center	Charleston	South Carolina	United States	29401
43	Medical University of South Carolina (MUSC)	Charleston	South Carolina	United States	29425
44	Erlanger Health System	Chattanooga	Tennessee	United States	37403
45	Urology of Virginia	Norfolk	Virginia	United States	23462
46	Seattle Urology Research Center	Burien	Washington	United States	98166
47	University of Washington School of Medicine	Seattle	Washington	United States	98195
48	Medical College of Wisconsin, Inc.	Milwaukee	Wisconsin	United States	53226
49	The Male Health Centre Euroscope Inc	Barrie	Ontario	Canada
50	J. Giddens Medicine Professional Corporation	Brampton	Ontario	Canada
51	G. Kenneth Jansz Medicine Professional Corporation	Burlington	Ontario	Canada
52	Urology Associates Urologic Medical Research	Kitchener	Ontario	Canada
53	London Health Sciences Centre	London	Ontario	Canada
54	Femalemale Health Centres	Oakville	Ontario	Canada
55	Princess Margaret Cancer Centre	Toronto	Ontario	Canada
56	Uro Laval	Laval	Quebec	Canada
57	Jewish General Hospital / McGill University	Montréal	Quebec	Canada
58	CHU de Québec -Hôtel-Dieu de Québec	Québec		Canada
59	Fakultni nemocnice Olomouc	Olomouc		Czechia
60	Fakultni nemocnice Ostrava	Ostrava		Czechia
61	Multiscan s.r.o.	Pardubice		Czechia
62	Urocentrum Plzen	Plzen		Czechia
63	Fakultni nemocnice v Motole	Praha		Czechia
64	Proton Therapy Center Czech s.r.o.	Praha		Czechia
65	Oblastni nemocnice Pribram a.s.	Příbram		Czechia
66	Krajska zdravotni a.s. - Masarykova nemocnice v Usti nad Labem o.z.	Ústí Nad Labem		Czechia
67	Keski-Suomen keskussairaala	Jyväskylä		Finland
68	Tampereen yliopistollinen	Tampere		Finland
69	Institut Sainte Catherine	Avignon		France
70	Groupe Hospitalier Pellegrin Tripode	Bordeaux		France
71	Hôpital Henri Mondor	Créteil		France
72	CHU de Grenoble - Hôpital Albert Michallon	Grenoble		France
73	CH de Libourne- Hopital Robert Boulin	Libourne		France
74	Hopital Claude Huriez - CHU Lille	Lille		France
75	Hopital Edouard Herriot - CHU Lyon	Lyon		France
76	Centre Hospitalier Régional Universitaire de Tours	Nantes		France
77	Hopital Bichat - Claude Bernard	Paris		France
78	Clinique Saint Jean Languedoc	Toulouse		France
79	Universitaetsklinikum Freiburg	Freiburg	Baden Wuerttemberg	Germany
80	Urologische Gemeinschaftspraxis	Kirchheim Unter Teck	Baden Wuerttemberg	Germany
81	Urologische Gemeinschaftspraxis	Herzogenaurach	Bayern	Germany
82	Staedtisches Klinikum Braunschweig GmbH - Standort Salzdahlumer	Braunschweig	Niedersachsen	Germany
83	Klinikum Oldenburg gGmbH	Oldenburg	Niedersachsen	Germany
84	Kliniken Maria Hilf GmbH	Moenchengladbach	Nordrhein Westfalen	Germany
85	Praxisklinik Urologie Rhein Ruhr	Mülheim	Nordrhein Westfalen	Germany
86	Krankenhaus Martha-Maria Halle-Doelau	Halle	Sachsen Anhalt	Germany
87	Facharztpraxis für Urologie	Lutherstadt Eisleben	Sachsen Anhalt	Germany
88	Staedtisches Klinikum Dresden Standort Dresden-Friedrichstadt	Dresden	Sachsen	Germany
89	Urologie am Nordplatz	Leipzig	Sachsen	Germany
90	Gynaekologisches Zentrum Bonn-Friedensplatz	Bonn		Germany
91	Central Clinic of Athens	Athens		Greece
92	General Hospital of Athens "Alexandra"	Athens		Greece
93	T.Y.P.E.T. Hygeias Melathron Hospital	Athens		Greece
94	University General Hospital of Heraklion	Heraklion		Greece
95	University of Patras Medical School	Patras		Greece
96	General Hospital Papageorgiou	Thessaloníki		Greece
97	Swietokrzyskie Centrum Onkologii	Kielce		Poland
98	Provita Profamilia	Piotrków Trybunalski		Poland
99	WroMedica	Wrocław		Poland
100	DERMED Centrum Medyczne Sp. z o.o.	Łódź		Poland
101	SBHI of Sverdiovsk Region "Sverdiovsk Regional Clinical Hospital #1	Ekaterinburg		Russian Federation
102	City Clinical Hospital n.a. Botkin	Moscow		Russian Federation
103	FSBI "Moscow scientific research oncology institute"	Moscow		Russian Federation
104	FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"	Moscow		Russian Federation
105	SBEI HPE "Moscow State Medical and Dentistry University n.a. A. I. Evdokimov"	Moscow		Russian Federation
106	FBHI Privolzhskiy District Medical Centre FMBA of Russia	Nizhniy Novgorod		Russian Federation
107	Medical Center Avitsenna	Novosibirsk		Russian Federation
108	BHI of Omsk region "Clinical Oncology Dispensary	Omsk		Russian Federation
109	FFSBI "The Nikiforov Russian Center of Emergency and Radiation Medicine"	Saint-Petersburg		Russian Federation
110	CUIMED s.r.o.	Bratislava		Slovakia
111	Urocentrum Bratislava s.r.o.	Bratislava		Slovakia
112	Vychodoslovensky onkologicky ustav, a.s.	Kosice		Slovakia
113	Nemocnica Kosice-Saca, a.s.	Košice		Slovakia
114	Zeleznicna nemocnica Kosice	Košice		Slovakia
115	UROCENTRUM LEVICE s.r.o.	Levice		Slovakia
116	UROAMB s.r.o.	Liptovský Mikuláš		Slovakia
117	Univerzitna nemocnica Martin	Martin		Slovakia
118	Fakultna nemocnica Nitra	Nitra		Slovakia
119	UROEXAM, spol. s r.o.	Nitra		Slovakia
120	MILAB s.r.o.	Prešov		Slovakia
121	MIRAMED s.r.o	Rimavska Sobota		Slovakia
122	UROCENTRUM SALA s.r.o.	Sala		Slovakia
123	Privatna Urologicka ambulancia	Trenčín		Slovakia
124	Fakultna nemocnica s poliklinikou Zilina	Žilina		Slovakia
125	Groote Schuur Hospital Department of Urology	Cape Town	Western Cape	South Africa
126	Prince Philip Hospital	Llanelli	Carmarthenshire	United Kingdom
127	Charing Cross Hospital	London	Greater London	United Kingdom
128	Scunthorpe General Hospital	Scunthorpe	Lincolnshire	United Kingdom
129	St Peter's Hospital	Chertsey	Surrey	United Kingdom
130	Royal Hallamshire Hospital	Sheffield	West Midlands	United Kingdom
131	Addenbrooke's Hospital	Cambridge		United Kingdom
132	Royal Devon and Exeter Hospital (Wonford)	Exeter		United Kingdom
133	Salford Royal	Salford		United Kingdom

Sponsors and Collaborators

Ferring Pharmaceuticals
Memorial Sloan Kettering Cancer Center
Duke Clinical Research Institute

Investigators

Study Director: Global Clinical Compliance, Ferring Pharmaceuticals
Principal Investigator: Susan Slovin, MD, Sidney Kimmel Center for Urologic and Prostate Cancers, Memorial Sloan Kettering Cancer Center
Principal Investigator: John Alexander, MD, MHS, Division of Cardiovascular Medicine, Duke Clinical Research Institute

Study Documents (Full-Text)

More Information

Publications

None provided.

Responsible Party:

Ferring Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT02663908

Other Study ID Numbers:

000108

First Posted:

Jan 26, 2016

Last Update Posted:

Jun 29, 2022

Last Verified:

May 1, 2022

Additional relevant MeSH terms:

Prostatic Neoplasms

Cardiovascular Diseases

Leuprolide

Study Results

Participant Flow

Recruitment Details	The trial was performed at 113 investigational sites in 12 countries between Apr 2016 to Mar 2021.
Pre-assignment Detail	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.

Arm/Group Title	Degarelix 240 mg/80 mg	Leuprolide 22.5 mg
Arm/Group Description	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 at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Period Title: Overall Study
STARTED	276	269
Full Analysis Set (FAS)	275	269
COMPLETED	244	245
NOT COMPLETED	32	24

Baseline Characteristics

Arm/Group Title	Degarelix 240 mg/80 mg	Leuprolide 22.5 mg	Total
Arm/Group Description	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: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.	Total of all reporting groups
Overall Participants	275	269	544
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	73.3 (7.28)	73.1 (7.16)	73.2 (7.22)
Age, Customized (Count of Participants)
< 75 years	153 55.6%	151 56.1%	304 55.9%
>= 75 years	122 44.4%	118 43.9%	240 44.1%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	275 100%	269 100%	544 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	16 5.8%	14 5.2%	30 5.5%
Not Hispanic or Latino	256 93.1%	254 94.4%	510 93.8%
Unknown or Not Reported	3 1.1%	1 0.4%	4 0.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 0.7%	0 0%	2 0.4%
Asian	3 1.1%	5 1.9%	8 1.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	16 5.8%	12 4.5%	28 5.1%
White	252 91.6%	251 93.3%	503 92.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 0.7%	1 0.4%	3 0.6%
Region of Enrollment (participants) [Number]
Greece	15 5.5%	15 5.6%	30 5.5%
Canada	25 9.1%	25 9.3%	50 9.2%
United States	111 40.4%	102 37.9%	213 39.2%
Czechia	22 8%	25 9.3%	47 8.6%
Finland	0 0%	1 0.4%	1 0.2%
Poland	3 1.1%	5 1.9%	8 1.5%
South Africa	2 0.7%	0 0%	2 0.4%
United Kingdom	8 2.9%	7 2.6%	15 2.8%
Slovakia	37 13.5%	45 16.7%	82 15.1%
France	16 5.8%	14 5.2%	30 5.5%
Germany	10 3.6%	9 3.3%	19 3.5%
Russia	26 9.5%	21 7.8%	47 8.6%
Baseline body mass index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	28.38 (5.057)	28.58 (4.589)	28.48 (4.828)
Stage of prostate cancer (Count of Participants)
Localized	138 50.2%	133 49.4%	271 49.8%
Locally Advanced	63 22.9%	80 29.7%	143 26.3%
Metastatic	63 22.9%	48 17.8%	111 20.4%
Not classifiable	11 4%	8 3%	19 3.5%
Eastern Cooperative Oncology Group (ECOG) performance score (Count of Participants)
0 score	178 64.7%	167 62.1%	345 63.4%
1 score	75 27.3%	80 29.7%	155 28.5%
2 score	8 2.9%	11 4.1%	19 3.5%
Testosterone levels (ng/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/dL]	353.6 (150.49)	351.6 (140.32)	352.6 (145.41)
Prostate Specific Antigen (PSA) (ng/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/mL]	119.7 (472.10)	59.9 (236.68)	90.2 (375.72)

Outcome Measures

1. Primary Outcome

Title	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
Description	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.
Time Frame	Randomization to Day 336 (end-of-trial)

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Degarelix 240 mg/80 mg	Leuprolide 22.5 mg
Arm/Group Description	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: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Measure Participants	275	269
Number [percentage of subjects]	5.5	4.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Degarelix 240 mg/80 mg, Leuprolide 22.5 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5294
	Comments
	Method	Log Rank
	Comments	The p-value of the log-rank test is based on comparison of the treatment groups stratified for age group and region.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.283
	Confidence Interval	(2-Sided) 95% 0.589 to 2.794
	Parameter Dispersion	Type: Value:
	Estimation Comments	Baseline hazards for the Cox regression were stratified over variables: age group and region.

2. Secondary Outcome

Title	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
Description	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.
Time Frame	Randomization to Day 336 (end-of-trial)

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Degarelix 240 mg/80 mg	Leuprolide 22.5 mg
Arm/Group Description	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: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Measure Participants	275	269
Number [percentage of subjects]	3.3	2.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Degarelix 240 mg/80 mg, Leuprolide 22.5 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7126
	Comments
	Method	Log Rank
	Comments	The p-value of the log-rank test is based on comparison of the treatment groups stratified for age group and region.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.204
	Confidence Interval	(2-Sided) 95% 0.448 to 3.234
	Parameter Dispersion	Type: Value:
	Estimation Comments	Baseline hazards for the Cox regression were stratified over variables: age group and region.

3. Secondary Outcome

Title	Time From Randomization to Confirmed (Adjudicated) CV-related Death; Percentage of Observed Subjects With Outcome Measure Events During the Trial
Description	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.
Time Frame	Randomization to Day 336 (end-of-trial)

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Degarelix 240 mg/80 mg	Leuprolide 22.5 mg
Arm/Group Description	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: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Measure Participants	275	269
Number [percentage of subjects]	0.4	1.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Degarelix 240 mg/80 mg, Leuprolide 22.5 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0853
	Comments
	Method	Log Rank
	Comments	The p-value of the log-rank test is based on comparison of the treatment groups stratified for age group and region.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.186
	Confidence Interval	(2-Sided) 95% 0.022 to 1.595
	Parameter Dispersion	Type: Value:
	Estimation Comments	Baseline hazards for the Cox regression were stratified over variables: age group and region.

4. Secondary Outcome

Title	Time From Randomization to the First Confirmed (Adjudicated) Myocardial Infarction; Percentage of Observed Subjects With Outcome Measure Events During the Trial
Description	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.
Time Frame	Randomization to Day 336 (end-of-trial)

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Degarelix 240 mg/80 mg	Leuprolide 22.5 mg
Arm/Group Description	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: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Measure Participants	275	269
Number [percentage of subjects]	1.8	1.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Degarelix 240 mg/80 mg, Leuprolide 22.5 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5196
	Comments
	Method	Log Rank
	Comments	The p-value of the log-rank test is based on comparison of the treatment groups stratified for age group and region.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.594
	Confidence Interval	(2-Sided) 95% 0.381 to 6.673
	Parameter Dispersion	Type: Value:
	Estimation Comments	Baseline hazards for the Cox regression were stratified over variables: age group and region.

5. Secondary Outcome

Title	Time From Randomization to the First Confirmed (Adjudicated) Stroke; Percentage of Observed Subjects With Outcome Measure Events During the Trial
Description	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.
Time Frame	Randomization to Day 336 (end-of-trial)

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Degarelix 240 mg/80 mg	Leuprolide 22.5 mg
Arm/Group Description	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: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Measure Participants	275	269
Number [percentage of subjects]	1.1	1.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Degarelix 240 mg/80 mg, Leuprolide 22.5 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8966
	Comments
	Method	Log Rank
	Comments	The p-value of the log-rank test is based on comparison of the treatment groups stratified for age group and region.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.899
	Confidence Interval	(2-Sided) 95% 0.181 to 4.457
	Parameter Dispersion	Type: Value:
	Estimation Comments	Baseline hazards for the Cox regression were stratified over variables: age group and region.

6. Secondary Outcome

Title	Time From Randomization to the First Confirmed (Adjudicated) Unstable Angina Requiring Hospitalization; Percentage of Observed Subjects With Outcome Measure Events During the Trial
Description	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.
Time Frame	Randomization to Day 336 (end-of-trial)

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Degarelix 240 mg/80 mg	Leuprolide 22.5 mg
Arm/Group Description	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: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Measure Participants	275	269
Number [percentage of subjects]	0.7	1.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Degarelix 240 mg/80 mg, Leuprolide 22.5 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3857
	Comments
	Method	Log Rank
	Comments	The p-value of the log-rank test is based on comparison of the treatment groups stratified for age group and region.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.480
	Confidence Interval	(2-Sided) 95% 0.088 to 2.620
	Parameter Dispersion	Type: Value:
	Estimation Comments	Baseline hazards for the Cox regression were stratified over variables: age group and region.

7. Secondary Outcome

Title	Time From Randomization to Death Due to Any Cause; Percentage of Observed Subjects With Outcome Measure Events During the Trial
Description	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.
Time Frame	Randomization to Day 336 (end-of-trial)

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Degarelix 240 mg/80 mg	Leuprolide 22.5 mg
Arm/Group Description	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: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Measure Participants	275	269
Number [percentage of subjects]	2.9	3.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Degarelix 240 mg/80 mg, Leuprolide 22.5 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7180
	Comments
	Method	Log Rank
	Comments	The p-value of the log-rank test is based on comparison of the treatment groups stratified for age group and region.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.839
	Confidence Interval	(2-Sided) 95% 0.324 to 2.176
	Parameter Dispersion	Type: Value:
	Estimation Comments	Baseline hazards for the Cox regression were stratified over variables: age group and region.

8. Secondary Outcome

Title	Testosterone Levels at Days 28, 168 and 336 in the Degarelix and Leuprolide Treatment Groups
Description	Median levels and interquartile ranges for serum testosterone at Days 28, 168, and 336 are presented.
Time Frame	Days 28, 168 and 336 (end-of-trial)

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Degarelix 240 mg/80 mg	Leuprolide 22.5 mg
Arm/Group Description	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: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Measure Participants	264	257
Day 28	8.650	14.410
Day 168	8.650	8.475
Day 336	9.855	8.650

9. Secondary Outcome

Title	Time From Randomization to Failure in Progression-free Survival (PFS); Percentage of Observed Subjects With Outcome Measure Events During the Trial
Description	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.
Time Frame	From randomization to end-of-trial for each subject (subjects not censored at Day 336)

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Degarelix 240 mg/80 mg	Leuprolide 22.5 mg
Arm/Group Description	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: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Measure Participants	275	269
Number [percentage of subjects]	8.7	10.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Degarelix 240 mg/80 mg, Leuprolide 22.5 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6701
	Comments
	Method	Log Rank
	Comments	The p-value of the log-rank test is based on comparison of the treatment groups stratified for age group and region.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.887
	Confidence Interval	(2-Sided) 95% 0.512 to 1.539
	Parameter Dispersion	Type: Value:
	Estimation Comments	Baseline hazards for the Cox regression were stratified over variables: age group and region.

10. Secondary Outcome

Title	Changes From Baseline in International Prostate Symptom Score (IPSS) Total and Quality of Life (QoL) Scores
Description	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.
Time Frame	Baseline to Days 168 and 336 (end-of-trial)

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Degarelix 240 mg/80 mg	Leuprolide 22.5 mg
Arm/Group Description	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: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Measure Participants	234	232
IPSS Total at Day 168	-0.000	0.907
IPSS, QoL at Day 168	-0.115	0.098
IPSS Total at Day 336	-0.795	0.121
IPSS, QoL at Day 336	-0.281	-0.234

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Degarelix 240 mg/80 mg, Leuprolide 22.5 mg
	Comments	IPSS Total at Day 168
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1193
	Comments
	Method	ANCOVA
	Comments	ANCOVA with the baseline score as a covariate, and treatment group, age group, region, visit, and treatment by visit interaction as factors.

Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	-0.907
	Confidence Interval	(2-Sided) 95% -2.048 to 0.235
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Degarelix 240 mg/80 mg, Leuprolide 22.5 mg
	Comments	IPSS, QoL at Day 168
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1080
	Comments
	Method	ANCOVA
	Comments	ANCOVA with the baseline score as a covariate, and treatment group, age group, region, visit, and treatment by visit interaction as factors.

Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	-0.213
	Confidence Interval	(2-Sided) 95% -0.473 to 0.047
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Degarelix 240 mg/80 mg, Leuprolide 22.5 mg
	Comments	IPSS Total at Day 336
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1256
	Comments
	Method	ANCOVA
	Comments	ANCOVA with the baseline score as a covariate, and treatment group, age group, region, visit, and treatment by visit interaction as factors.

Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	-0.916
	Confidence Interval	(2-Sided) 95% -2.089 to 0.257
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Degarelix 240 mg/80 mg, Leuprolide 22.5 mg
	Comments	IPSS, QoL at Day 336
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7261
	Comments
	Method	ANCOVA
	Comments	ANCOVA with the baseline score as a covariate, and treatment group, age group, region, visit, and treatment by visit interaction as factors.

Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	-0.047
	Confidence Interval	(2-Sided) 95% -0.312 to 0.218
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Total Number of CV-related Hospitalization Events Over the Duration of the Trial
Description	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.
Time Frame	First dose of IMP to Day 336 (end-of-trial)

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	Degarelix 240 mg/80 mg	Leuprolide 22.5 mg
Arm/Group Description	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: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Measure Participants	275	269
Number [Events]	15	17

12. Secondary Outcome

Title	Total Number of Coronary Artery By-pass Grafting (CABG) or Percutaneous Coronary Intervention (PCI) Procedures Over the Duration of the Trial
Description	The total number of CABG or PCI procedures observed for each subject over the duration of the trial
Time Frame	First dose of IMP to Day 336 (end-of-trial)

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	Degarelix 240 mg/80 mg	Leuprolide 22.5 mg
Arm/Group Description	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: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Measure Participants	275	269
Number [Events]	3	6

13. Secondary Outcome

Title	Total Number of CV-related Emergency Room (ER) Visit Events Over the Duration of the Trial
Description	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.
Time Frame	First dose of IMP to Day 336 (end-of-trial)

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	Degarelix 240 mg/80 mg	Leuprolide 22.5 mg
Arm/Group Description	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: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Measure Participants	275	269
Number [Events]	8	2

14. Secondary Outcome

Title	Change in Utility, Based on EuroQol Group 5 Dimensions 5 Levels Questionnaire (EQ-5D-5L)
Description	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.
Time Frame	Baseline to Day 336 (end-of-trial)

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Degarelix 240 mg/80 mg	Leuprolide 22.5 mg
Arm/Group Description	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: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Measure Participants	243	239
Least Squares Mean (95% Confidence Interval) [QALY]	0.794	0.796

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Degarelix 240 mg/80 mg, Leuprolide 22.5 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.9110
	Comments
	Method	ANCOVA
	Comments	Compared using an ANCOVA model, where the QALY is the dependent variable and adjusted for treatment group, age group and region, respectively.

Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-0.002
	Confidence Interval	(2-Sided) 95% -0.036 to 0.032
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Changes From Baseline in Duke Activity Status Index (DASI) Global Score
Description	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.
Time Frame	Baseline to Days 168 and 336 (end-of-trial)

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Degarelix 240 mg/80 mg	Leuprolide 22.5 mg
Arm/Group Description	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: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Measure Participants	234	232
Change in DASI to Day 168	-2.65	-1.08
Change in DASI to Day 336	-2.18	-3.01

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Degarelix 240 mg/80 mg, Leuprolide 22.5 mg
	Comments	DASI at Day 168
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0936
	Comments
	Method	ANCOVA
	Comments	ANCOVA with the baseline score as a covariate, and treatment group, age group, region, visit, and treatment by visit interaction as factors.

Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	-1.57
	Confidence Interval	(2-Sided) 95% -3.41 to 0.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Degarelix 240 mg/80 mg, Leuprolide 22.5 mg
	Comments	DASI at Day 336
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4000
	Comments
	Method	ANCOVA
	Comments	ANCOVA with the baseline score as a covariate, and treatment group, age group, region, visit, and treatment by visit interaction as factors.

Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95% -1.11 to 2.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

Title	Changes From Baseline in Cardiac Anxiety Questionnaire (CAQ) Global Score and Score Per Domain
Description	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.
Time Frame	Baseline to Days 168 and 336 (end-of-trial)

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Degarelix 240 mg/80 mg	Leuprolide 22.5 mg
Arm/Group Description	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: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Measure Participants	234	232
CAQ global score (Day 168)	0.034	-0.011
CAQ domain score for Attention (Day 168)	0.030	-0.006
CAQ domain score for Avoidance (Day 168)	0.155	0.039
CAQ domain score for Fear (Day 168)	-0.036	-0.048
CAQ global score (Day 336)	0.102	0.051
CAQ domain score for Attention (Day 336)	0.023	-0.015
CAQ domain score for Avoidance (Day 336)	0.228	0.220
CAQ domain score for Fear (Day 336)	0.075	-0.018

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Degarelix 240 mg/80 mg, Leuprolide 22.5 mg
	Comments	CAQ Global Score at Day 168
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2535
	Comments
	Method	ANCOVA
	Comments	ANCOVA with the baseline score as a covariate, and treatment group, age group, region, visit, and treatment by visit interaction as factors.

Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	0.045
	Confidence Interval	(2-Sided) 95% -0.032 to 0.122
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Degarelix 240 mg/80 mg, Leuprolide 22.5 mg
	Comments	CAQ domain score for Attention at Day 168
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4370
	Comments
	Method	ANCOVA
	Comments	ANCOVA with the baseline score as a covariate, and treatment group, age group, region, visit, and treatment by visit interaction as factors.

Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	0.036
	Confidence Interval	(2-Sided) 95% -0.055 to 0.127
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Degarelix 240 mg/80 mg, Leuprolide 22.5 mg
	Comments	CAQ domain score for Avoidance at Day 168
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0852
	Comments
	Method	ANCOVA
	Comments	ANCOVA with the baseline score as a covariate, and treatment group, age group, region, visit, and treatment by visit interaction as factors.

Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	0.116
	Confidence Interval	(2-Sided) 95% -0.016 to 0.248
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Degarelix 240 mg/80 mg, Leuprolide 22.5 mg
	Comments	CAQ domain score for Fear at Day 168
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8156
	Comments
	Method	ANCOVA
	Comments	ANCOVA with the baseline score as a covariate, and treatment group, age group, region, visit, and treatment by visit interaction as factors.

Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	0.012
	Confidence Interval	(2-Sided) 95% -0.087 to 0.111
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Degarelix 240 mg/80 mg, Leuprolide 22.5 mg
	Comments	CAQ Global Score at Day 336
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2299
	Comments
	Method	ANCOVA
	Comments	ANCOVA with the baseline score as a covariate, and treatment group, age group, region, visit, and treatment by visit interaction as factors.

Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	0.051
	Confidence Interval	(2-Sided) 95% -0.033 to 0.135
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Degarelix 240 mg/80 mg, Leuprolide 22.5 mg
	Comments	CAQ domain score for Attention at Day 336
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4440
	Comments
	Method	ANCOVA
	Comments	ANCOVA with the baseline score as a covariate, and treatment group, age group, region, visit, and treatment by visit interaction as factors.

Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	0.038
	Confidence Interval	(2-Sided) 95% -0.060 to 0.136
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Degarelix 240 mg/80 mg, Leuprolide 22.5 mg
	Comments	CAQ domain score for Avoidance at Day 336
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.9172
	Comments
	Method	ANCOVA
	Comments	ANCOVA with the baseline score as a covariate, and treatment group, age group, region, visit, and treatment by visit interaction as factors.

Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	0.007
	Confidence Interval	(2-Sided) 95% -0.131 to 0.146
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Degarelix 240 mg/80 mg, Leuprolide 22.5 mg
	Comments	CAQ domain score for Fear at Day 336
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1028
	Comments
	Method	ANCOVA
	Comments	ANCOVA with the baseline score as a covariate, and treatment group, age group, region, visit, and treatment by visit interaction as factors.

Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	0.093
	Confidence Interval	(2-Sided) 95% -0.019 to 0.204
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Secondary Outcome

Title	Number of Subjects With Adverse Events (AEs)
Description	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.
Time Frame	Start of IMP treatment until 3 months after last dosing of IMP

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Degarelix 240 mg/80 mg	Leuprolide 22.5 mg
Arm/Group Description	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: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Measure Participants	275	269
AEs	250	228
SAEs	47	44
AE leading to death	11	9

18. Secondary Outcome

Title	Intensity of AEs
Description	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.
Time Frame	Start of IMP treatment until 3 months after last dosing of IMP

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Degarelix 240 mg/80 mg	Leuprolide 22.5 mg
Arm/Group Description	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: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Measure Participants	275	269
Mild AE	224	200
Moderate AE	160	135
Severe AE	59	55

19. Secondary Outcome

Title	Changes in Vital Signs
Description	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.
Time Frame	Baseline to Day 336 (end-of-trial)

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Degarelix 240 mg/80 mg	Leuprolide 22.5 mg
Arm/Group Description	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: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
Measure Participants	196	193
Count of Participants [Participants]	0 0%	1 0.4%

Adverse Events

	Degarelix 240 mg/80 mg		Leuprolide 22.5 mg
Time Frame	Start of IMP treatment until 3 months after last dosing of IMP
Adverse Event Reporting Description	Adverse events were recorded from signing of the informed consent until end-of-trial. 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 (defined above). Non-fatal serious adverse events (SAEs) of myocardial infarction, stroke, and unstable angina constituted exceptions to the SAE reporting (6 events in the degarelix group, 10 in the leuprolide group).

Arm/Group Title	Degarelix 240 mg/80 mg		Leuprolide 22.5 mg
Arm/Group Description	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: Leuprolide at dose of 22.5 mg administered as intramuscular depot injection every 3 months throughout the trial.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/275 (4%)		9/269 (3.3%)
Serious Adverse Events
	Degarelix 240 mg/80 mg		Leuprolide 22.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	47/275 (17.1%)		44/269 (16.4%)
Cardiac disorders
Cardiac failure chronic	3/275 (1.1%)	4	1/269 (0.4%)	1
Cardiac failure	1/275 (0.4%)	1	2/269 (0.7%)	2
Atrial flutter	2/275 (0.7%)	2	0/269 (0%)	0
Atrioventricular block complete	2/275 (0.7%)	2	0/269 (0%)	0
Bradycardia	2/275 (0.7%)	2	0/269 (0%)	0
Acute myocardial infarction	0/275 (0%)	0	1/269 (0.4%)	1
Angina pectoris	1/275 (0.4%)	1	0/269 (0%)	0
Arrhythmia	0/275 (0%)	0	1/269 (0.4%)	1
Ischaemic cardiomyopathy	1/275 (0.4%)	1	0/269 (0%)	0
Sinus node dysfunction	1/275 (0.4%)	1	0/269 (0%)	0
Supraventricular tachycardia	1/275 (0.4%)	2	0/269 (0%)	0
Tachyarrhythmia	1/275 (0.4%)	1	0/269 (0%)	0
Ventricular fibrillation	0/275 (0%)	0	1/269 (0.4%)	1
Gastrointestinal disorders
Diarrhoea	1/275 (0.4%)	1	0/269 (0%)	0
Gastric ulcer haemorrhage	0/275 (0%)	0	1/269 (0.4%)	1
Haematochezia	0/275 (0%)	0	1/269 (0.4%)	1
Ileus	0/275 (0%)	0	1/269 (0.4%)	1
Inguinal hernia	1/275 (0.4%)	1	0/269 (0%)	0
Intestinal obstruction	0/275 (0%)	0	1/269 (0.4%)	1
Rectal haemorrhage	1/275 (0.4%)	1	0/269 (0%)	0
Umbilical hernia	0/275 (0%)	0	1/269 (0.4%)	1
General disorders
Death	3/275 (1.1%)	3	1/269 (0.4%)	1
Malaise	1/275 (0.4%)	1	1/269 (0.4%)	1
Injection site swelling	0/275 (0%)	0	1/269 (0.4%)	1
Non-cardiac chest pain	1/275 (0.4%)	1	0/269 (0%)	0
Oedema peripheral	1/275 (0.4%)	1	0/269 (0%)	0
Pyrexia	1/275 (0.4%)	1	0/269 (0%)	0
Hepatobiliary disorders
Cholecystitis	0/275 (0%)	0	1/269 (0.4%)	1
Hepatic failure	1/275 (0.4%)	1	0/269 (0%)	0
Infections and infestations
Pneumonia	5/275 (1.8%)	5	3/269 (1.1%)	4
Sepsis	2/275 (0.7%)	2	3/269 (1.1%)	3
COVID-19 pneumonia	2/275 (0.7%)	2	0/269 (0%)	0
Urinary tract infection	1/275 (0.4%)	1	1/269 (0.4%)	1
Bacteraemia	1/275 (0.4%)	1	0/269 (0%)	0
Cellulitis	0/275 (0%)	0	1/269 (0.4%)	1
Cystitis	0/275 (0%)	0	1/269 (0.4%)	1
Diverticulitis intestinal haemorrhagic	1/275 (0.4%)	1	0/269 (0%)	0
Enterococcal sepsis	0/275 (0%)	0	1/269 (0.4%)	1
Intervertebral discitis	1/275 (0.4%)	1	0/269 (0%)	0
Osteomyelitis	1/275 (0.4%)	1	0/269 (0%)	0
Pyelonephritis	0/275 (0%)	0	1/269 (0.4%)	1
Respiratory tract infection	0/275 (0%)	0	1/269 (0.4%)	1
Hepatic echinococciasis	0/275 (0%)	0	1/269 (0.4%)	1
Injury, poisoning and procedural complications
Fall	2/275 (0.7%)	2	0/269 (0%)	0
Anastomotic ulcer haemorrhage	1/275 (0.4%)	1	0/269 (0%)	0
Cervical vertebral fracture	0/275 (0%)	0	1/269 (0.4%)	1
Femoral neck fracture	1/275 (0.4%)	1	0/269 (0%)	0
Femur fracture	0/275 (0%)	0	1/269 (0.4%)	1
Hip fracture	0/275 (0%)	0	1/269 (0.4%)	1
Lumbar vertebral fracture	1/275 (0.4%)	1	0/269 (0%)	0
Rib fracture	1/275 (0.4%)	1	0/269 (0%)	0
Skin laceration	0/275 (0%)	0	1/269 (0.4%)	1
Spinal compression fracture	0/275 (0%)	0	1/269 (0.4%)	1
Subdural haematoma	1/275 (0.4%)	1	0/269 (0%)	0
Upper limb fracture	1/275 (0.4%)	1	0/269 (0%)	0
Investigations
Heart rate irregular	0/275 (0%)	0	1/269 (0.4%)	1
Metabolism and nutrition disorders
Hyperkalaemia	0/275 (0%)	0	2/269 (0.7%)	2
Failure to thrive	0/275 (0%)	0	1/269 (0.4%)	1
Hypocalcaemia	0/275 (0%)	0	1/269 (0.4%)	1
Hypokalaemia	0/275 (0%)	0	1/269 (0.4%)	1
Musculoskeletal and connective tissue disorders
Back pain	1/275 (0.4%)	1	2/269 (0.7%)	2
Bone pain	1/275 (0.4%)	1	0/269 (0%)	0
Rhabdomyolysis	0/275 (0%)	0	1/269 (0.4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain neoplasm	0/275 (0%)	0	1/269 (0.4%)	1
Hodgkin's disease	0/275 (0%)	0	1/269 (0.4%)	1
Pancreatic carcinoma	0/275 (0%)	0	1/269 (0.4%)	1
Nervous system disorders
Syncope	0/275 (0%)	0	4/269 (1.5%)	4
Cerebrovascular accident	1/275 (0.4%)	1	1/269 (0.4%)	1
Cerebral haemorrhage	1/275 (0.4%)	1	0/269 (0%)	0
Cognitive disorder	0/275 (0%)	0	1/269 (0.4%)	1
Sciatica	1/275 (0.4%)	2	0/269 (0%)	0
Toxic encephalopathy	1/275 (0.4%)	1	0/269 (0%)	0
Tremor	1/275 (0.4%)	1	0/269 (0%)	0
Psychiatric disorders
Suicidal ideation	1/275 (0.4%)	1	1/269 (0.4%)	1
Completed suicide	0/275 (0%)	0	1/269 (0.4%)	1
Renal and urinary disorders
Acute kidney injury	0/275 (0%)	0	3/269 (1.1%)	3
Urinary retention	2/275 (0.7%)	2	1/269 (0.4%)	1
Nephrolithiasis	1/275 (0.4%)	1	0/269 (0%)	0
Renal failure	1/275 (0.4%)	1	0/269 (0%)	0
Urinary tract obstruction	0/275 (0%)	0	1/269 (0.4%)	1
Reproductive system and breast disorders
Prostatitis	1/275 (0.4%)	1	0/269 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	2/275 (0.7%)	2	1/269 (0.4%)	1
Acute respiratory failure	1/275 (0.4%)	1	1/269 (0.4%)	1
Pneumothorax	0/275 (0%)	0	2/269 (0.7%)	2
Respiratory failure	2/275 (0.7%)	2	0/269 (0%)	0
Acute respiratory distress syndrome	1/275 (0.4%)	1	0/269 (0%)	0
Chronic obstructive pulmonary disease	0/275 (0%)	0	1/269 (0.4%)	1
Pulmonary oedema	1/275 (0.4%)	1	0/269 (0%)	0
Vascular disorders
Hypotension	2/275 (0.7%)	2	1/269 (0.4%)	1
Deep vein thrombosis	0/275 (0%)	0	2/269 (0.7%)	2
Hypertension	0/275 (0%)	0	1/269 (0.4%)	1
Hypovolaemic shock	1/275 (0.4%)	1	0/269 (0%)	0
Peripheral artery thrombosis	1/275 (0.4%)	1	0/269 (0%)	0
Peripheral ischaemia	1/275 (0.4%)	1	0/269 (0%)	0
Thrombosis	1/275 (0.4%)	1	0/269 (0%)	0
Other (Not Including Serious) Adverse Events
	Degarelix 240 mg/80 mg		Leuprolide 22.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	250/275 (90.9%)		228/269 (84.8%)
Gastrointestinal disorders
Diarrhoea	23/275 (8.4%)	26	26/269 (9.7%)	28
Constipation	18/275 (6.5%)	21	20/269 (7.4%)	20
Nausea	19/275 (6.9%)	21	11/269 (4.1%)	12
General disorders
Fatigue	50/275 (18.2%)	57	34/269 (12.6%)	35
Injection site pain	73/275 (26.5%)	232	6/269 (2.2%)	7
Injection site erythema	58/275 (21.1%)	163	1/269 (0.4%)	1
Injection site swelling	27/275 (9.8%)	62	3/269 (1.1%)	3
Asthenia	15/275 (5.5%)	18	8/269 (3%)	9
Oedema peripheral	8/275 (2.9%)	8	15/269 (5.6%)	17
Injection site induration	19/275 (6.9%)	79	2/269 (0.7%)	3
Pyrexia	16/275 (5.8%)	20	5/269 (1.9%)	6
Infections and infestations
Urinary tract infection	20/275 (7.3%)	26	13/269 (4.8%)	14
Musculoskeletal and connective tissue disorders
Arthralgia	24/275 (8.7%)	29	16/269 (5.9%)	17
Back pain	22/275 (8%)	25	19/269 (7.1%)	22
Pain in extremity	15/275 (5.5%)	19	11/269 (4.1%)	13
Nervous system disorders
Dizziness	20/275 (7.3%)	20	14/269 (5.2%)	16
Psychiatric disorders
Insomnia	12/275 (4.4%)	12	14/269 (5.2%)	14
Renal and urinary disorders
Pollakiuria	24/275 (8.7%)	25	28/269 (10.4%)	31
Dysuria	25/275 (9.1%)	27	21/269 (7.8%)	24
Haematuria	8/275 (2.9%)	17	15/269 (5.6%)	17
Nocturia	8/275 (2.9%)	8	14/269 (5.2%)	14
Vascular disorders
Hot flush	107/275 (38.9%)	112	120/269 (44.6%)	127
Hypertension	17/275 (6.2%)	27	23/269 (8.6%)	31

Limitations/Caveats

The trial was terminated prematurely due to a slower than anticipated recruitment rate and a lower than anticipated observed CV event rate. Approximately 900 patients were planned to be included, however, at the time of stopping screening and recruitment 216 patients had completed the trial, 292 were ongoing, and 37 were withdrawn. The Sponsor decision to stop the trial was not based on any safety concerns, any knowledge of the results, or influenced by issues imposed by the COVID-19 pandemic.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.

Results Point of Contact

Name/Title	Global Clinical Compliance
Organization	Ferring Pharmaceuticals
Phone
Email	DK0-Disclosure@ferring.com

Responsible Party:

Ferring Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT02663908

Other Study ID Numbers:

000108

First Posted:

Jan 26, 2016

Last Update Posted:

Jun 29, 2022

Last Verified:

May 1, 2022

PRONOUNCE: A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease

Study Details

Study Description

Brief Summary

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion Criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

More Information

Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Statistical Analysis 4

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Statistical Analysis 4

Statistical Analysis 5

Statistical Analysis 6

Statistical Analysis 7

Statistical Analysis 8

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

More Information

Certain Agreements

Results Point of Contact