Neoadjuvant Study Investigating Degarelix in Patients Suffering From Prostate Cancer

• Sponsor: Ferring Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00833248
• Collaborator: (none)
• Enrollment: 246
• Locations: 66
• Arms: 2
• Duration (Months): 29
• Patients Per Site: 3.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this phase 3B trial was to see how well a new trial drug (degarelix) works in terms of reducing the size of the prostate volume in prostate cancer patients who were scheduled to undergo subsequent radiotherapy for treatment of their prostate cancer. Prior to receiving radiotherapy, it is recommended that patients with intermediate to high risk prostate cancer are pre-treated with hormone therapy (so-called neoadjuvant therapy) which is known to reduce the size of the prostate and thereby decrease the required radiation field and enable a more safe and effective treatment. In this trial, participants were randomly selected (like flipping a coin) to receive either degarelix given alone or a standard hormone therapy (combination of goserelin and bicalutamide. The treatment was given for three months and the prostate size was measured by ultra sound at the beginning and at the end of the trial. The participants were required to come to the clinic for 5 or 6 visits during the three months.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Degarelix; Drug: Goserelin; Drug: Bicalutamide	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 246 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomised, Parallel Arm, Open-label Trial Comparing Degarelix With Goserelin Plus Anti-androgen Flare Protection (Bicalutamide), in Terms of Prostate Size Reduction in Prostate Cancer Patients of Intermediate-to-high Risk, Who Require Neoadjuvant Hormone Therapy Prior to Radiotherapy (Curative Intent)
• Study Start Date: Apr 1, 2009
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Sep 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Degarelix 240 mg/80 mg The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The second and third doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections on Days 28 and 56, respectively.	Drug: Degarelix; The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The second and third doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections on Days 28 and 56, respectively.; Other Names: FE200486 Firmagon
Active Comparator: Goserelin (3.6 mg) + bicalutamide (50 mg) On Day 0, the participants began once-daily oral (p.o.) treatment with bicalutamide as anti-androgen flare protection. This treatment continued for 2 weeks after the first dose of goserelin (i.e. 17 days in total). On Day 3, the first goserelin implant was inserted s.c. into the abdominal wall. The second and third doses of goserelin were administered on Days 31 and 59, respectively.	Drug: Goserelin; Goserelin implants (3.6 mg) were inserted s.c. into the abdominal wall every 28 days. The first dose was administered on Day 3. The second and third doses of goserelin were administered on Days 31 and 59, respectively.; Other Names: Zoladex ; Drug: Bicalutamide; On Day 0, participants began once-daily per-oral (p.o.) treatment with bicalutamide (50 mg) as anti-androgen flare protection; this treatment continued for 14 days after the first dose of goserelin.; Other Names: Casodex

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Prostate Size Based on Trans Rectal Ultra Sound (TRUS) at Week 12 (Full Analysis Set) [After treatment of 12 weeks compared to Baseline]

   TRUS is a method of measuring the size of the prostate.

2. Change From Baseline in Prostate Size Based on Trans Rectal Ultra Sound (TRUS) at Week 12 (Per Protocol Analysis Set) [After treatment of 12 weeks compared to Baseline]

   TRUS is a method of measuring the size of the prostate.

Secondary Outcome Measures

1. Change From Baseline in Total International Prostate Symptom Score (IPSS) at Week 4, 8, and 12 [After treatment of 4, 8, and 12 weeks compared to Baseline]

   The IPSS is a tool commonly used to assess the severity of lower urinary tract symptoms (LUTS), and to monitor the progress of the disease once treatment has been initiated. The participant completes a questionnaire containing 7 questions regarding incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia. Each question is assigned a score of 0-5. The total score is then classified according to the following scale: 0 to 7 = mildly symptomatic; 8 to 19 = moderately symptomatic; and 20 to 35 = severely symptomatic.

2. Change From Baseline in Serum Testosterone Levels During the Study [After treatment of 4, 8, and 12 weeks compared to Baseline]

3. Change From Baseline in Serum Prostate-Specific Antigen (PSA) Levels During the Study [After treatment of 4, 8, and 12 weeks compared to Baseline]

4. Change From Baseline in Serum Oestradiol Levels During the Study [After treatment of 4, 8, and 12 weeks compared to Baseline]

5. Change From Baseline in Quality of Life (QoL) Related to Urinary Symptoms at Each Visit [After treatment of 4, 8, and 12 weeks compared to Baseline]

   The IPSS questionnaire included an additional single question to assess the participant's QoL in relation to his urinary symptoms. The question was: 'If you were to spend the rest of your life with your urinary condition the way it is now, how would you feel about that?' The possible answers to this question ranged from 'delighted' (a score of '0') to 'terrible' (a score of '6').

6. Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight [Baseline to 12 weeks of treatment]

   This outcome measure included incidence of markedly abnormal changes in blood pressure (systolic and diastolic), pulse, and body weight. The table presents the number of participants with normal baseline and at least one post-baseline markedly abnormal value.

7. Number of Participants With Markedly Abnormal Values in Safety Laboratory Variables [Baseline to 12 weeks of treatment]

   The figures present the number of participants who had abnormal (defined as above upper limit of normal range (ULN)) levels of safety laboratory variables. Only the laboratory variables that had at least one percentage of participants in either group with abnormal value are presented, more variables were included in the study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient has given written informed consent before any trial-related activity is performed.

• Has a confirmed prostate cancer in which this type of treatment is needed.

Exclusion Criteria:

• Previous treatment for prostate cancer

• Previous trans-urethral resection of the prostate

• Patients who are lymph node positive or have other metastatic disease

• Use of urethral catheter

• Current treatment with a 5-alpha reductase inhibitor or α-adrenoceptor antagonist.

• History of severe untreated asthma, anaphylactic reactions, or severe urticaria and/or angioedema.

• Hypersensitivity towards any component of the investigational product

• Other previous cancers within the last five years with the exception of prostate cancer and some types of skin cancer.

• Certain risk factors for abnormal heart rhythms/QT prolongation (corrected QT interval over 450 msec., Torsades de Pointes or use of certain medications with potential risk)

• Clinical disorders other than prostate cancer including but not limited to renal, haematological, gastrointestinal, endocrine, cardiac, neurological, psychiatric disease, alcohol or drug abuse or other conditionals as judged by the investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alabama Research Center	Birmingham	Alabama	United States	35209
2	Urology Centers of Alabama	Homewood	Alabama	United States	35209
3	Alaska Urological Association	Anchorage	Alaska	United States	99508
4	Arizona Urologic Specialists	Tuscon	Arizona	United States	85712
5	Orange County Urology	Lagua Hills	California	United States	92653
6	Tri-Valley Urology Medical Group	Murrieta	California	United States	92563
7	Connecticut Clinical Research Center	Middlebury	Connecticut	United States	06762
8	South Florida Medical Research	Aventura	Florida	United States	33180
9	DCT -Celebration, LLC dba Discovery Clinical Trials	Celebration	Florida	United States	34747
10	Pinellas Urology Inc.	St. Petersburg	Florida	United States	33710
11	Palm Beach Urology Associates	Wellington	Florida	United States	33449
12	Summit Research Institute	Bloomington	Indiana	United States	47403
13	Northeast Indiana Research	Fort Wayne	Indiana	United States	46825
14	Urology Center Research Institute	Englewood	New Jersey	United States	07631
15	Urology Group of New Mexico	Albuquerque	New Mexico	United States	87109
16	Premier Medical Group of Hudson	Columbia	New York	United States	12601
17	University Urology Associates	New York	New York	United States	10016
18	Urology Associates	Nashville	Tennessee	United States	37209
19	Urology of Virginia	Norfolk	Virginia	United States	23502
20	Hopital Jean Minjoz	Besancon		France	25000
21	Institut Bergonié	Bordeaux Cedex		France	33076
22	Centre Francois Baclesse	Caen		France	14000
23	CHU Henri Mondor	Creteil		France	94000
24	Centre Oscar Lambret	Lille		France	59020
25	Centre Leon Berard	Lyon		France	69008
26	Hopital de la Timone	Marseille, Cedex 5		France	13385
27	CRLC Val d'Aurelle Oncology Radiotherapy	Montpellier		France	CX5 34298
28	Hôpital Tenon	Paris		France	75000
29	Hôpital Saint Louis, Radiotherapy Departement	Paris		France	75010
30	Clinique Francheville	Perigueux		France	24000
31	CHU La Milétrie, Oncology Radiotherapy	Poitiers		France	86000
32	Centre de Lutte Contre le Cancer Nantes-Atlantique Centre René Gauducheau	Saint Herblain Cedex		France
33	Institut de Cancérologie de la Loire	Saint Priest en Jarez		France	CX 42271
34	Clinique Saint Brieuc	St Brieuc Cedex		France	22015
35	Centre Paul Strauss	Strassbourg		France	67085
36	Centre de radiologie Saint Louis	Toulon		France	83100
37	Clinique du Parc	Toulouse		France	31400
38	IGR	Villejuif		France	94805
39	Charité-Universitätsmedizin, Campus Benjamin Franklin Klinik für Urologie	Berlin		Germany	D-12203
40	Städtisches Klinikum Braunschweig	Braunschweig		Germany	D-38126
41	Universitätsklinikum Dresden, Klinik und Poliklinik für Urologie	Dresden		Germany	D-01307
42	Universitätsklinikum Ulm, Klinik für Strahlentherapie und Radioonkologie	Ulm		Germany	D-89081
43	General University Hospital of Alexandroupolis	Alexandroupolis		Greece	68100
44	General Hospital of Athens, "Sismanogleio", University of Athens, Marouse	Athens		Greece	15126
45	University General Hospital of Loannina, Medical School	Loannina		Greece	45110
46	University General Hospital of Patras	Patras		Greece	26504
47	Albert Schweitzer Ziekenhuis, Ioc., Dordwijk	Dordrecht		Netherlands	3318 AT
48	Groene Hart Ziekenhuis, urology	Gouda		Netherlands	2803 HH
49	Franciscus Gasthuis, Dept. urology	Rotterdam		Netherlands	3045 PM
50	Maastad Ziekenhuis, Ioc. Clara	Rotterdam		Netherlands	3078HT
51	Vlietland Ziekenhuis, Dept. urology	Schiedam		Netherlands	3118 JH
52	St. Elisabeth Ziekenhuis Tilburg	Tilburg		Netherlands	5000 LC
53	Hospital de la Santa Creu i Sant Pau	Barcelona		Spain	08025
54	Hospital Universitari Vall d´Hebron	Barcelona		Spain	08035
55	Hospital Universitario La Paz	Madrid		Spain	28046
56	Fundación IVO	Valencia		Spain	46009
57	Kent Oncology Centre Maidstone Hospital	Maidstone	Kent	United Kingdom	ME16 9QQ
58	Mount Vernon Cancer Center	Northwood	Middlesex	United Kingdom	HA6 2RN
59	Oncology Royal United Hospital Bath NHS Trust	Bath		United Kingdom	BA1 3NG
60	Addenbrooke's Hospital, Oncology Centre	Cambridge		United Kingdom	CB2 0QQ
61	St. James' University Hospital	Leeds		United Kingdom	LS9 7TF
62	The Royal Marsden NHS, Foundation Trust	London		United Kingdom	SW3 6JJ
63	Charing Cross Hospital	London		United Kingdom	W6 8FR
64	Northern Centre for Cancer Treatment, Newcastle General Hospital	Newcastle upon Tyne		United Kingdom	NE4 6BE
65	Southhampton General Hospital, Cancer Care Directorate, Southhampton Oncology Centre	Southhampton		United Kingdom	SO16 6YD
66	Velindre Hospital, Cardiff University	Whitchurch		United Kingdom	CF14 2TL

Sponsors and Collaborators

• Ferring Pharmaceuticals

Investigators

• Study Director: Clinical Development Support, Ferring Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ferring Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00833248
• Other Study ID Numbers: FE200486 CS30; 2008-005232-33
• First Posted: Feb 2, 2009
• Last Update Posted: Oct 4, 2012
• Last Verified: Sep 1, 2012

• Additional relevant MeSH terms: Prostatic Neoplasms; Goserelin; Bicalutamide

Study Results

Participant Flow

Recruitment Details	The participants were recruited by outpatient urologists, radiotherapists or oncologists. A total of 240 patients were to be randomised in a 3:1 ratio to one of two treatment groups (180 participants were to be treated with degarelix; 60 participants were to be treated with goserelin+bicalutamide). The recruitment period was April 2009 - June 2011.

Arm/Group Title	Degarelix 240 mg/80 mg	Goserelin (3.6 mg) + Bicalutamide (50 mg)
Arm/Group Description	The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The second and third doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections on Days 28 and 56, respectively.	On Day 0, the participants began once-daily oral (p.o.) treatment with bicalutamide as anti-androgen flare protection. This treatment continued for 2 weeks after the first dose of goserelin (i.e. 17 days in total). On Day 3, the first goserelin implant was inserted s.c. into the abdominal wall. The second and third doses of goserelin were administered on Days 31 and 59, respectively.
Period Title: Overall Study
STARTED	181	65
Full Analysis Set (FAS)	180	64
Per Protocol (PP) Analysis Set	164	57
Safety Analysis Set	181	64
COMPLETED	177	62
NOT COMPLETED	4	3

Baseline Characteristics

Arm/Group Title	Degarelix 240 mg/80 mg	Goserelin (3.6 mg) + Bicalutamide (50 mg)	Total
Arm/Group Description	The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The second and third doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections on Days 28 and 56, respectively.	On Day 0, the participants began once-daily oral (p.o.) treatment with bicalutamide as anti-androgen flare protection. This treatment continued for 2 weeks after the first dose of goserelin (i.e. 17 days in total). On Day 3, the first goserelin implant was inserted s.c. into the abdominal wall. The second and third doses of goserelin were administered on Days 31 and 59, respectively.	Total of all reporting groups
Overall Participants	180	64	244
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	70.6 (6.37)	70.8 (5.96)	70.6 (6.25)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	180 100%	64 100%	244 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.6%	0 0%	1 0.4%
Asian	1 0.6%	0 0%	1 0.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	15 8.3%	3 4.7%	18 7.4%
White	163 90.6%	61 95.3%	224 91.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	45 25%	16 25%	61 25%
France	60 33.3%	22 34.4%	82 33.6%
Greece	5 2.8%	2 3.1%	7 2.9%
Spain	9 5%	3 4.7%	12 4.9%
Netherlands	11 6.1%	2 3.1%	13 5.3%
Germany	9 5%	4 6.3%	13 5.3%
United Kingdom	41 22.8%	15 23.4%	56 23%
Body Weight (kilogram) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram]	83.6 (14.2)	80.9 (12.4)	82.9 (13.8)
Body Mass Index (kilogram per square meter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram per square meter]	27.8 (3.99)	26.8 (3.69)	27.5 (3.93)
Gleason Score (participants) [Number]
Gleason Score 2-6	41 22.8%	12 18.8%	53 21.7%
Gleason Score 7	97 53.9%	42 65.6%	139 57%
Gleason Score 8-10	42 23.3%	10 15.6%	52 21.3%
Stage of Prostate Cancer (participants) [Number]
Localized	111 61.7%	41 64.1%	152 62.3%
Locally Advanced	63 35%	20 31.3%	83 34%
Metastatic	0 0%	0 0%	0 0%
Not Classifiable	6 3.3%	3 4.7%	9 3.7%
Serum Testosterone Levels (nanograms per milliliter) [Median (Full Range) ]
Median (Full Range) [nanograms per milliliter]	3.92	4.42	4.06
Serum Prostate-Specific Antigen (PSA) Levels (nanograms per millilter) [Median (Full Range) ]
Median (Full Range) [nanograms per millilter]	10	9.75	9.95
Serum Oestradiol Levels (nanograms per deciliter) [Median (Full Range) ]
Median (Full Range) [nanograms per deciliter]	1.9	1.9	1.9
Prostate Volume (milliliter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [milliliter]	50.9 (20.3)	52.5 (18.8)	51.3 (19.9)
Total International Prostate Symptom Score (IPSS) (scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [scores on a scale]	9.5 (6.71)	8.46 (6.3)	9.23 (6.61)
Quality of Life (QoL) Related to Urinary Symptoms (scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [scores on a scale]	2.27 (1.63)	1.94 (1.56)	2.19 (1.62)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Prostate Size Based on Trans Rectal Ultra Sound (TRUS) at Week 12 (Full Analysis Set)
Description	TRUS is a method of measuring the size of the prostate.
Time Frame	After treatment of 12 weeks compared to Baseline

Outcome Measure Data

Analysis Population Description

FAS, Observed Case (OC) i.e. only participants with a reported value were included in the analysis.

Arm/Group Title	Degarelix 240 mg/80 mg	Goserelin (3.6 mg) + Bicalutamide (50 mg)
Arm/Group Description	The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The second and third doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections on Days 28 and 56, respectively.	On Day 0, the participants began once-daily oral (p.o.) treatment with bicalutamide as anti-androgen flare protection. This treatment continued for 2 weeks after the first dose of goserelin (i.e. 17 days in total). On Day 3, the first goserelin implant was inserted s.c. into the abdominal wall. The second and third doses of goserelin were administered on Days 31 and 59, respectively.
Measure Participants	176	62
Mean (Standard Deviation) [milliliter]	-36.0 (14.5)	-35.3 (16.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Degarelix 240 mg/80 mg, Goserelin (3.6 mg) + Bicalutamide (50 mg)
	Comments	FAS. Estimates from analysis of variance with treatment as factors and baseline IPSS and baseline Prostate volume as covariates.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was to be established if the treatment difference in adjusted (for baseline volume, and baseline total IPSS) mean percentage reduction was significantly greater (two-sided at α=0.05 level) than Δ = 10 points (non-inferiority margin) in both the FAS and PP analyses sets.
Statistical Test of Hypothesis	p-Value	0.8942
	Comments
	Method	ANCOVA
	Comments	The baseline IPSS and baseline Prostate volume were used as covariates and treatment was used as a factor in the analysis.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -4.74 to 4.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Change From Baseline in Prostate Size Based on Trans Rectal Ultra Sound (TRUS) at Week 12 (Per Protocol Analysis Set)
Description	TRUS is a method of measuring the size of the prostate.
Time Frame	After treatment of 12 weeks compared to Baseline

Outcome Measure Data

Analysis Population Description

FAS, OC.

Arm/Group Title	Degarelix 240 mg/80 mg	Goserelin (3.6 mg) + Bicalutamide (50 mg)
Arm/Group Description	The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The second and third doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections on Days 28 and 56, respectively.	On Day 0, the participants began once-daily oral (p.o.) treatment with bicalutamide as anti-androgen flare protection. This treatment continued for 2 weeks after the first dose of goserelin (i.e. 17 days in total). On Day 3, the first goserelin implant was inserted s.c. into the abdominal wall. The second and third doses of goserelin were administered on Days 31 and 59, respectively.
Measure Participants	154	54
Mean (Standard Deviation) [milliliter]	-36.2 (14.5)	-35.4 (16.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Degarelix 240 mg/80 mg, Goserelin (3.6 mg) + Bicalutamide (50 mg)
	Comments	PP analysis set. Estimates from analysis of variance with treatment as factors and baseline IPSS and baseline Prostate volume as covariates.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was to be established if the treatment difference in adjusted (for baseline volume, and baseline total IPSS) mean percentage reduction was significantly greater (two-sided at α=0.05 level) than Δ = 10 points (non-inferiority margin) in both the FAS and PP analyses sets.
Statistical Test of Hypothesis	p-Value	0.9123
	Comments
	Method	ANCOVA
	Comments	The baseline IPSS and baseline Prostate volume were used as covariates and treatment was used as a factor in the analysis.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.268
	Confidence Interval	(2-Sided) 95%; -5.05 to 4.52
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Total International Prostate Symptom Score (IPSS) at Week 4, 8, and 12
Description	The IPSS is a tool commonly used to assess the severity of lower urinary tract symptoms (LUTS), and to monitor the progress of the disease once treatment has been initiated. The participant completes a questionnaire containing 7 questions regarding incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia. Each question is assigned a score of 0-5. The total score is then classified according to the following scale: 0 to 7 = mildly symptomatic; 8 to 19 = moderately symptomatic; and 20 to 35 = severely symptomatic.
Time Frame	After treatment of 4, 8, and 12 weeks compared to Baseline

Outcome Measure Data

Analysis Population Description

FAS, OC.

Arm/Group Title	Degarelix 240 mg/80 mg	Goserelin (3.6 mg) + Bicalutamide (50 mg)
Arm/Group Description	The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The second and third doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections on Days 28 and 56, respectively.	On Day 0, the participants began once-daily oral (p.o.) treatment with bicalutamide as anti-androgen flare protection. This treatment continued for 2 weeks after the first dose of goserelin (i.e. 17 days in total). On Day 3, the first goserelin implant was inserted s.c. into the abdominal wall. The second and third doses of goserelin were administered on Days 31 and 59, respectively.
Measure Participants	177	63
Week 4	-0.21 (5.05)	0.36 (4.83)
Week 8	-1.53 (5.43)	0.02 (5.41)
Week 12	-1.71 (5.54)	0.11 (5.13)

4. Secondary Outcome

Title	Change From Baseline in Serum Testosterone Levels During the Study
Time Frame	After treatment of 4, 8, and 12 weeks compared to Baseline

Outcome Measure Data

Analysis Population Description

FAS, OC.

Arm/Group Title	Degarelix 240 mg/80 mg	Goserelin (3.6 mg) + Bicalutamide (50 mg)
Arm/Group Description	The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The second and third doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections on Days 28 and 56, respectively.	On Day 0, the participants began once-daily oral (p.o.) treatment with bicalutamide as anti-androgen flare protection. This treatment continued for 2 weeks after the first dose of goserelin (i.e. 17 days in total). On Day 3, the first goserelin implant was inserted s.c. into the abdominal wall. The second and third doses of goserelin were administered on Days 31 and 59, respectively.
Measure Participants	170	63
Week 4	-3.8	-4.22
Week 8	-3.77	-4.26
Week 12	-3.81	-4.3

5. Secondary Outcome

Title	Change From Baseline in Serum Prostate-Specific Antigen (PSA) Levels During the Study
Time Frame	After treatment of 4, 8, and 12 weeks compared to Baseline

Outcome Measure Data

Analysis Population Description

FAS, OC.

Arm/Group Title	Degarelix 240 mg/80 mg	Goserelin (3.6 mg) + Bicalutamide (50 mg)
Arm/Group Description	The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The second and third doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections on Days 28 and 56, respectively.	On Day 0, the participants began once-daily oral (p.o.) treatment with bicalutamide as anti-androgen flare protection. This treatment continued for 2 weeks after the first dose of goserelin (i.e. 17 days in total). On Day 3, the first goserelin implant was inserted s.c. into the abdominal wall. The second and third doses of goserelin were administered on Days 31 and 59, respectively.
Measure Participants	172	62
Week 4	-6.3	-5.9
Week 8	-7.95	-8.8
Week 12	-8.35	-9.05

6. Secondary Outcome

Title	Change From Baseline in Serum Oestradiol Levels During the Study
Time Frame	After treatment of 4, 8, and 12 weeks compared to Baseline

Outcome Measure Data

Analysis Population Description

FAS, OC.

Arm/Group Title	Degarelix 240 mg/80 mg	Goserelin (3.6 mg) + Bicalutamide (50 mg)
Arm/Group Description	The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The second and third doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections on Days 28 and 56, respectively.	On Day 0, the participants began once-daily oral (p.o.) treatment with bicalutamide as anti-androgen flare protection. This treatment continued for 2 weeks after the first dose of goserelin (i.e. 17 days in total). On Day 3, the first goserelin implant was inserted s.c. into the abdominal wall. The second and third doses of goserelin were administered on Days 31 and 59, respectively.
Measure Participants	124	36
Week 4	-1.55	-1.65
Week 8	-1.6	-1.65
Week 12	-1.55	-1.6

7. Secondary Outcome

Title	Change From Baseline in Quality of Life (QoL) Related to Urinary Symptoms at Each Visit
Description	The IPSS questionnaire included an additional single question to assess the participant's QoL in relation to his urinary symptoms. The question was: 'If you were to spend the rest of your life with your urinary condition the way it is now, how would you feel about that?' The possible answers to this question ranged from 'delighted' (a score of '0') to 'terrible' (a score of '6').
Time Frame	After treatment of 4, 8, and 12 weeks compared to Baseline

Outcome Measure Data

Analysis Population Description

FAS, OC.

Arm/Group Title	Degarelix 240 mg/80 mg	Goserelin (3.6 mg) + Bicalutamide (50 mg)
Arm/Group Description	The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The second and third doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections on Days 28 and 56, respectively.	On Day 0, the participants began once-daily oral (p.o.) treatment with bicalutamide as anti-androgen flare protection. This treatment continued for 2 weeks after the first dose of goserelin (i.e. 17 days in total). On Day 3, the first goserelin implant was inserted s.c. into the abdominal wall. The second and third doses of goserelin were administered on Days 31 and 59, respectively.
Measure Participants	179	63
Week 4	-0.07 (1.31)	0.16 (0.92)
Week 8	-0.24 (1.34)	0.05 (1.11)
Week 12	-0.33 (1.46)	0.16 (1.4)

8. Secondary Outcome

Title	Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight
Description	This outcome measure included incidence of markedly abnormal changes in blood pressure (systolic and diastolic), pulse, and body weight. The table presents the number of participants with normal baseline and at least one post-baseline markedly abnormal value.
Time Frame	Baseline to 12 weeks of treatment

Outcome Measure Data

Analysis Population Description

Safety analysis set.

Arm/Group Title	Degarelix 240 mg/80 mg	Goserelin (3.6 mg) + Bicalutamide (50 mg)
Arm/Group Description	The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The second and third doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections on Days 28 and 56, respectively.	On Day 0, the participants began once-daily oral (p.o.) treatment with bicalutamide as anti-androgen flare protection. This treatment continued for 2 weeks after the first dose of goserelin (i.e. 17 days in total). On Day 3, the first goserelin implant was inserted s.c. into the abdominal wall. The second and third doses of goserelin were administered on Days 31 and 59, respectively.
Measure Participants	181	64
Diastolic blood pressure <=50 and decrease >=15	0 0%	0 0%
Diastolic blood pressure >=105 and increase >=15	3 1.7%	0 0%
Systolic blood pressure <=90 and decrease >=20	0 0%	0 0%
Systolic blood pressure >=180 and increase >=20	1 0.6%	1 1.6%
Heart rate <=50 and decrease >=15	1 0.6%	1 1.6%
Heart rate >=120 and increase >=15	0 0%	0 0%
Body weight decrease of >=7 percent	3 1.7%	2 3.1%
Body weight increase of >=7 percent	5 2.8%	0 0%

9. Secondary Outcome

Title	Number of Participants With Markedly Abnormal Values in Safety Laboratory Variables
Description	The figures present the number of participants who had abnormal (defined as above upper limit of normal range (ULN)) levels of safety laboratory variables. Only the laboratory variables that had at least one percentage of participants in either group with abnormal value are presented, more variables were included in the study.
Time Frame	Baseline to 12 weeks of treatment

Outcome Measure Data

Analysis Population Description

Safety analysis set.

Arm/Group Title	Degarelix 240 mg/80 mg	Goserelin (3.6 mg) + Bicalutamide (50 mg)
Arm/Group Description	The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The second and third doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections on Days 28 and 56, respectively.	On Day 0, the participants began once-daily oral (p.o.) treatment with bicalutamide as anti-androgen flare protection. This treatment continued for 2 weeks after the first dose of goserelin (i.e. 17 days in total). On Day 3, the first goserelin implant was inserted s.c. into the abdominal wall. The second and third doses of goserelin were administered on Days 31 and 59, respectively.
Measure Participants	181	64
B-Haematocrit (Ratio) <=0.37	31 17.2%	8 12.5%
B-Haemoglobin (g/L) <=115	4 2.2%	1 1.6%
S-Alanine aminotransferase (IU/L) >3 x ULN	1 0.6%	1 1.6%
S-Potassium (mmol/L) >=5.8	4 2.2%	1 1.6%
S-Urea nitrogen (mmol/L) >=10.7	10 5.6%	3 4.7%

Adverse Events

Time Frame	12 weeks.
Adverse Event Reporting Description	Each participant's condition was monitored throughout the trial from the time of signing the informed consent until the end of the follow-up period. The investigator was to record all adverse events (AEs) in the AE log of the participant's Case Report Form.
Arm/Group Title	Degarelix 240 mg/80 mg		Goserelin (3.6 mg) + Bicalutamide (50 mg)
Arm/Group Description	The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The second and third doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections on Days 28 and 56, respectively.		On Day 0, the participants began once-daily oral (p.o.) treatment with bicalutamide as anti-androgen flare protection. This treatment continued for 2 weeks after the first dose of goserelin (i.e. 17 days in total). On Day 3, the first goserelin implant was inserted s.c. into the abdominal wall. The second and third doses of goserelin were administered on Days 31 and 59, respectively.
All Cause Mortality
	Degarelix 240 mg/80 mg		Goserelin (3.6 mg) + Bicalutamide (50 mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Degarelix 240 mg/80 mg		Goserelin (3.6 mg) + Bicalutamide (50 mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/181 (3.9%)		0/64 (0%)
Cardiac disorders
Atrial fibrillation	1/181 (0.6%)	1	0/64 (0%)	0
Eye disorders
Retinal detachment	1/181 (0.6%)	1	0/64 (0%)	0
Investigations
Alanine aminotransferase increased	1/181 (0.6%)	1	0/64 (0%)	0
Aspartate aminotransferase increased	1/181 (0.6%)	1	0/64 (0%)	0
Blood alkaline phosphatase increased	1/181 (0.6%)	1	0/64 (0%)	0
Gamma-glutamyltransferase increased	1/181 (0.6%)	1	0/64 (0%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain	1/181 (0.6%)	1	0/64 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer	1/181 (0.6%)	1	0/64 (0%)	0
Lung neoplasm malignant	1/181 (0.6%)	1	0/64 (0%)	0
Renal and urinary disorders
Urinary retention	1/181 (0.6%)	1	0/64 (0%)	0
Other (Not Including Serious) Adverse Events
	Degarelix 240 mg/80 mg		Goserelin (3.6 mg) + Bicalutamide (50 mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	158/181 (87.3%)		53/64 (82.8%)
General disorders
Injection site pain	60/181 (33.1%)	93	1/64 (1.6%)	1
Injection site erythema	45/181 (24.9%)	73	0/64 (0%)	0
Asthenia	13/181 (7.2%)	15	6/64 (9.4%)	6
Injection site pruritus	13/181 (7.2%)	19	0/64 (0%)	0
Fatigue	11/181 (6.1%)	13	6/64 (9.4%)	6
Injection site swelling	11/181 (6.1%)	17	0/64 (0%)	0
Psychiatric disorders
Libido decreased	12/181 (6.6%)	12	4/64 (6.3%)	4
Renal and urinary disorders
Pollakiuria	11/181 (6.1%)	13	4/64 (6.3%)	4
Reproductive system and breast disorders
Erectile dysfunction	14/181 (7.7%)	15	7/64 (10.9%)	7
Vascular disorders
Hot flush	108/181 (59.7%)	132	40/64 (62.5%)	46

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review the draft manuscript prior to publication and can request delay of publication where any contents are deemed patentable by the sponsor or confidential to the sponsor. Comments will be given within four weeks from receipt of the draft manuscript. Additional time may be required to allow Ferring to seek patent protection of the invention.