DELUTS: A Trial of Degarelix in Men With Lower Urinary Tract Symptoms (LUTS) Associated With Benign Prostatic Hyperplasia (BPH)

• Sponsor: Ferring Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00947882
• Collaborator: (none)
• Enrollment: 404
• Locations: 47
• Arms: 4
• Duration (Months): 22
• Patients Per Site: 8.6
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

A dose-finding, multi-centre, double-blind, randomised, parallel, placebo-controlled trial to investigate efficacy and safety of degarelix in men with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH)

Condition or Disease	Intervention/Treatment	Phase
Lower Urinary Tract Symptoms (LUTS)	Drug: Placebo; Drug: Degarelix 10 mg; Drug: Degarelix 20 mg; Drug: Degarelix 30 mg	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 404 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Dose-Finding, Multi-Centre, Double-Blind, Randomised, Parallel, Placebo-Controlled Trial to Investigate Efficacy and Safety of Degarelix in Men With Lower Urinary Tract Symptoms (LUTS) Associated With Benign Prostatic Hyperplasia (BPH)
• Study Start Date: Aug 1, 2009
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo	Drug: Placebo; Mannitol 50 mg/mL solution
Experimental: Degarelix 10 mg	Drug: Degarelix 10 mg; 10 mg degarelix, 40 mg/mL solution; Other Names: FE200486 Firmagon
Experimental: Degarelix 20 mg	Drug: Degarelix 20 mg; 20 mg degarelix, 40 mg/mL solution; Other Names: FE200486 Firmagon
Experimental: Degarelix 30 mg	Drug: Degarelix 30 mg; 30 mg degarelix, 40 mg/mL solution; Other Names: FE200486 Firmagon

Outcome Measures

Primary Outcome Measures

1. Mean Change in International Prostate Symptom Score (IPSS) [From Baseline to Month 3 after Dosing]

   This outcome measure was used to assess the dose-response of the 3 degarelix dose groups in terms of severity of lower urinary tract symptoms (LUTS) and progress of the disease process, versus the placebo group. One treatment month equals 28 days. The IPSS questionnaire is a tool commonly used to assess the severity of LUTS, and to monitor the progress of the symptoms during treatment. It contains 7 questions regarding incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia. Each question is assigned a score of 0-5 (i.e. minimum total score is 0 and the maximum score is 35), where "0" corresponds to a response of "not at all" for the first six symptoms and "none" for nocturia, and "5" corresponds to a response of "almost always" for the first six symptoms and "5 times or more" for nocturia. The IPSS also includes a question to evaluate a patient's quality of life in relation to his urinary symptoms, which is not included in the total IPSS score.

Secondary Outcome Measures

1. Mean Change in IPSS [From Baseline to Month 4, Month 5 and Month 6 after Dosing]

   This secondary outcome measure was used to assess the maintained dose-response of the 3 degarelix dose groups in terms of severity of LUTS and progress of the disease process, versus the placebo group.

2. Odds Ratio (as Compared to Placebo) of Treatment Response in IPSS [At Month 3, Month 4, Month 5 and Month 6 after Dosing]

   A 3-point reduction in IPSS score compared to baseline is defined as a clinically meaningful treatment response. Percentage of participants who met criteria for a clinically meaningful treatment response and odds ratios of treatment responses between each degarelix dose group and the placebo group are presented.

3. Mean Percentage Change in Total Prostate Volume (TPV) [From Baseline to Month 3 and Month 6 after Dosing]

   TPV was measured directly by standardised trans-rectal ultrasound (TRUS).

4. Mean Change in Maximum Urinary Flow (Qmax) [From Baseline to Month 3 and Month 6 after Dosing]

   Urinary flow rate (mL/second) was measured using uroflowmetry performed according to the recommendation from the International Continence Society (ICS).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Signed informed consent obtained before any trial-related activity is performed

• Men, aged 50 or older

• Clinical signs and symptoms of BPH for ≥6 months

• Moderate to severe LUTS at screening, as defined by International Prostate Symptom Score (IPSS) ≥13

• An IPSS QoL score of ≥3 at screening

• Prostate specific antigen (PSA) at screening ≤10 ng/mL (responsibility of the Investigator to rule out prostate cancer when PSA is >4 ng/mL, except in the USA where patients with a PSA >4 and ≤10 ng/mL should undergo a prostatic biopsy or have a negative prostatic biopsy within 12 months prior to participation in the trial)

• Maximum urinary flow (Qmax) ranging between 5 to 15 mL/second with a minimum voided volume >125 mL at screening

Exclusion Criteria:

• Post void residual volume (PVR) >250 mL

• Stone in the bladder or urethra causing symptoms

• Acute or chronic prostatitis

• Interstitial cystitis / painful bladder syndrome

• Acute or recurrent urinary tract infections

• History of acute urinary retention (AUR)

• Lower urinary tract instrumentation (including prostate biopsy) within 30 days of dosing at Visit 2

• Clinical evidence of any of the following urinary tract conditions:

1. Mullerian duct cysts

2. Atonic, decompensated, or hypocontractile bladder

3. Detrusor-sphincter dyssynergia (contraction of the detrusor without sphincter relaxation)

• History of any of the following pelvic conditions:

1. Pelvic surgery or any other pelvic procedure, including radical prostatectomy, pelvic surgery for removal of malignancy, or open lower colonic or rectal surgery

2. Pelvic radiotherapy

3. Any prior surgical procedure of the urinary tract, including minimally invasive LUTS/BPH therapies

4. Lower tract malignancy or trauma

• Clinically significant microscopic haematuria at screening

• History of significant renal insufficiency, defined as receiving renal dialysis or having an estimated creatinine clearance <30 mL/minute at screening

• Systolic blood pressure >180 or <90 mmHg or diastolic blood pressure >110 or <50 mmHg at screening or malignant hypertension

• Any causes other than BPH, which may affect evaluation of symptoms of urine flow (e.g. neurogenic bladder, bladder neck contracture, urethral stricture, and bladder malignancy) as judged by the Investigator

• Use of any prohibited therapies

• Elevated liver function tests at screening:

1. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) >2 times the upper limit of normal

2. Total bilirubin >1.5 times the upper limit of normal

• QTc interval on the screening ECG >450 ms, or a family history of long QT syndrome

• Any clinically significant disorder (other than BPH) including, but not limited to, renal, haematological, gastrointestinal, endocrine, cardiac, neurological, or psychiatric disease, or any other condition, which may affect the patient's health or the outcome of the trial as judged by the Investigator

• Diagnosed cancer within the last 5 years except for adequately managed basal cell carcinoma and squamous cell carcinoma of the skin

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

• Mental incapacity or language barrier precluding adequate understanding or co-operation

• History or current evidence of drug, alcohol, or substance abuse within 6 months prior to screening

• Hypersensitivity towards any component of the investigational medicinal product (IMP)

• Previous participation in any degarelix trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Urology Centers of Alabama, PC	Homewood	Alabama	United States
2	Coastal Clinical Research Inc	Mobile	Alabama	United States
3	California Professional Research	Newport Beach	California	United States
4	Genitourinary Surgical Consultants	Denver	Colorado	United States
5	Urology Associates , PC	Englewood	Colorado	United States
6	South Florida Medical Research	Aventura	Florida	United States
7	Winter Park Urology Associates	Orlando	Florida	United States
8	Pinellas Urology Inc	St Petersburg	Florida	United States
9	Florida Urology Partners	Tampa	Florida	United States
10	Northwestern University	Chicago	Illinois	United States
11	Weill Cornell Medical College New York Presbyterian	New York	New York	United States
12	Hudson Valley Urology, PC	Poughkeepsie	New York	United States
13	Duke University Medical Center	Durham	North Carolina	United States
14	Patient Priority Clinical Sites, LLC	Cincinnati	Ohio	United States
15	Carolina Urologic Research Center	Myrtle Beach	South Carolina	United States
16	Middelheim Antwerp	Antwerpen		Belgium
17	UZ Brussel	Brussels		Belgium
18	Can-Med Clinical Research Inc	Victoria	British Columbia	Canada
19	Dr Steinhoff Clinical Research	Victoria	British Columbia	Canada
20	Male/Female Health and Research Centre	Barrie	Ontario	Canada
21	Bramalea Medical Centre	Brampton	Ontario	Canada
22	Brandford Urology Research	Brantford	Ontario	Canada
23	Guelp Urology	Guelph	Ontario	Canada
24	Centre for Applied Urological Research	Kingston	Ontario	Canada
25	Investigational Site	North Bay	Ontario	Canada
26	Female/Male Health Centres	Oakville	Ontario	Canada
27	Mahoney Medicine Professional Corporation	Ottawa	Ontario	Canada
28	Todd Webster Ontario Inc	Owen Sound	Ontario	Canada
29	Anthony Skehan Medicine Professional Corporation	Thunder Bay	Ontario	Canada
30	The Male Health Centre	Toronto	Ontario	Canada
31	McGill University Health Centre	Montreal	Quebec	Canada
32	Ultra-Med Inc	Point-Claire	Quebec	Canada
33	Urologie, Male namesti 1783	Benesov		Czech Republic
34	Urocentrum Brno, Purkynova 35e	Brno		Czech Republic
35	Prvni privatni chirurgicke centrum SANUS, Labská kotlina I/1220	Hradec Králové		Czech Republic
36	Urologicka ambulance, Litomerice (Halek)	Litomerice		Czech Republic
37	Slezska nemocnice, prospevkova organizace, Urologicke oddeleni	Opava		Czech Republic
38	Androgeos - soukrome urologicke a andrologicke cen, Na valech 4/289	Praha		Czech Republic
39	Urocentrum, Karlovo namesti 3	Praha		Czech Republic
40	Urologica ambulance, Praha 10	Praha		Czech Republic
41	Ústecké urocentrum, Ústi nad Labem (Liehne)	Ústi nad Labem		Czech Republic
42	Urologia, A.O. San Giuseppe Moscati, Avellino	Avellino		Italy
43	Unità Operativa di Urologia, Azienda Opsedaliera Luigi Sacco	Milano		Italy
44	Unità Operativa di Urologia, Ospedale San Raffaele	Milano		Italy
45	Akademia Medyczna w Gdansku	Gdansk		Poland
46	Publiczny Specjalistyczny ZOZ	Inowroclaw		Poland
47	Samodzielny Publiczny Szpital Kliniczny nr.1	Zabrze		Poland

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: NCT00947882
• Other Study ID Numbers: FE200486 CS36; 2009-012325-11; 104367
• First Posted: Jul 28, 2009
• Last Update Posted: Jun 8, 2015
• Last Verified: May 1, 2015

• Additional relevant MeSH terms: Prostatic Hyperplasia; Hyperplasia; Lower Urinary Tract Symptoms

Study Results

Participant Flow

Recruitment Details	Patients who met the eligibility criteria were randomised in a 1:1:1:1 manner to 1 of the 4 treatment groups in this trial. The randomisation was stratified by region (North America and Europe) and prostate volume (<30 mL and ≥30 mL). 404 patients were randomised and received a single dose of placebo, 10 mg, 20 mg, or 30 mg degarelix.

Arm/Group Title	Placebo	Degarelix 10 mg	Degarelix 20 mg	Degarelix 30 mg
Arm/Group Description	Placebo: Mannitol 50 mg/mL solution. The dose was administered as a subcutaneous (s.c.) injection in the abdominal region.	Degarelix 10 mg: 10 mg degarelix, 40 mg/mL solution. The dose was administered as a s.c. injection in the abdominal region.	Degarelix 20 mg: 20 mg degarelix, 40 mg/mL solution. The dose was administered as a s.c. injection in the abdominal region.	Degarelix 30 mg: 30 mg degarelix, 40 mg/mL solution. The dose was administered as a s.c. injection in the abdominal region.
Period Title: Overall Study
STARTED	100	101	101	102
Full Analysis Set (FAS)	100	101	100	102
Actual Treatment	98	101	100	105
Safety Analysis Set	98	101	100	105
Visit 12, Month 6	93	91	90	95
COMPLETED	26	24	22	20
NOT COMPLETED	74	77	79	82

Baseline Characteristics

Arm/Group Title	Placebo	Degarelix 10 mg	Degarelix 20 mg	Degarelix 30 mg	Total
Arm/Group Description	Placebo: Mannitol 50 mg/mL solution. The dose was administered as a s.c. injection in the abdominal region.	Degarelix 10 mg: 10 mg degarelix, 40 mg/mL solution. The dose was administered as a s.c. injection in the abdominal region.	Degarelix 20 mg: 20 mg degarelix, 40 mg/mL solution. The dose was administered as a s.c. injection in the abdominal region.	Degarelix 30 mg: 30 mg degarelix, 40 mg/mL solution. The dose was administered as a s.c. injection in the abdominal region.	Total of all reporting groups
Overall Participants	100	101	100	102	403
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.2 (7.86)	64.9 (7.89)	65.7 (7.12)	65.4 (7.56)	65.3 (7.59)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%
Male	100 100%	101 100%	100 100%	102 100%	403 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 1%	4 4%	0 0%	4 3.9%	9 2.2%
Not Hispanic or Latino	99 99%	97 96%	100 100%	98 96.1%	394 97.8%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 1%	0 0%	1 1%	2 0.5%
Asian	0 0%	1 1%	1 1%	2 2%	4 1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	4 4%	3 3%	3 3%	3 2.9%	13 3.2%
White	96 96%	96 95%	96 96%	96 94.1%	384 95.3%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
North America	59 59%	60 59.4%	61 61%	60 58.8%	240 59.6%
Europe	41 41%	41 40.6%	39 39%	42 41.2%	163 40.4%
Baseline Body Mass Index (BMI) ((kg/m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [(kg/m^2)]	28.5 (3.66)	28.4 (3.93)	27.9 (3.84)	28.2 (4.81)	28.2 (4.08)
Baseline International Prostate Symptom Scores (IPSS) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	19.1 (4.38)	19.9 (5.21)	19.6 (4.42)	19.8 (4.88)	19.6 (4.73)
Baseline Total Prostate Volume (TPV) (mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL]	41.6 (17.8)	42.9 (18.8)	42.3 (20.2)	42.1 (20.2)	42.2 (19.2)
Baseline Maximum Urinary Flow (Qmax) (mL/sec) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL/sec]	10.2 (2.51)	10.3 (2.65)	10.6 (4.58)	10.2 (2.44)	10.3 (3.05)

Outcome Measures

1. Primary Outcome

Title	Mean Change in International Prostate Symptom Score (IPSS)
Description	This outcome measure was used to assess the dose-response of the 3 degarelix dose groups in terms of severity of lower urinary tract symptoms (LUTS) and progress of the disease process, versus the placebo group. One treatment month equals 28 days. The IPSS questionnaire is a tool commonly used to assess the severity of LUTS, and to monitor the progress of the symptoms during treatment. It contains 7 questions regarding incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia. Each question is assigned a score of 0-5 (i.e. minimum total score is 0 and the maximum score is 35), where "0" corresponds to a response of "not at all" for the first six symptoms and "none" for nocturia, and "5" corresponds to a response of "almost always" for the first six symptoms and "5 times or more" for nocturia. The IPSS also includes a question to evaluate a patient's quality of life in relation to his urinary symptoms, which is not included in the total IPSS score.
Time Frame	From Baseline to Month 3 after Dosing

Outcome Measure Data

Analysis Population Description

FAS. The "as planned" patient allocation for treatment groups was used in the efficacy analyses (please refer to the Baseline Characteristics section).

Arm/Group Title	Placebo	Degarelix 10 mg	Degarelix 20 mg	Degarelix 30 mg
Arm/Group Description	Mannitol 50 mg/mL solution. The dose was administered as a subcutaneous (s.c.) injection in the abdominal region.	Degarelix 10 mg: 10 mg degarelix, 40 mg/mL solution. The dose was administered as a subcutaneous (s.c.) injection in the abdominal region.	Degarelix 20 mg: 20 mg degarelix, 40 mg/mL solution. The dose was administered as a s.c. injection in the abdominal region.	Degarelix 30 mg: 30 mg degarelix, 40 mg/mL solution. The dose was administered as a s.c. injection in the abdominal region.
Measure Participants	100	101	100	102
Mean (Standard Deviation) [percentage change from baseline]	-4.46 (5.34)	-5.65 (6.03)	-6.11 (5.7)	-5.88 (5.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 30 mg
	Comments	Analysis of Covariance (ANCOVA) of the change from baseline in IPSS at Month 3 in the FAS population using the Last Observation Carried Forward (LOCF) method, including the baseline IPSS as adjusting covariate and treatment group, prostate volume stratum (<30 mL and ≥30 mL), and region (North America and Europe) as factors.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0911
	Comments	P-value based on Williams' extended trend test of comparison vs. placebo at Month 3. No adjustment for multiple comparisons was made.
	Method	Step-down, Williams' extended trend test
	Comments	Step-down procedure (starting with 30 mg vs. placebo) to identify the minimum effective dose. The step-down testing protects the type I error rate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.30
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment difference between "Degarelix 30 mg" and "Placebo" at Month 3.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 20 mg
	Comments	Analysis of Covariance (ANCOVA) of the change from baseline in IPSS at Month 3 in the FAS population using the Last Observation Carried Forward (LOCF) method, including the baseline IPSS as adjusting covariate and treatment group, prostate volume stratum (<30 mL and ≥30 mL), and region (North America and Europe) as factors.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0865
	Comments	P-value based on Williams' extended trend test of comparison vs. placebo at Month 3. No adjustment for multiple comparisons was made.
	Method	Step-down, Williams' extended trend test
	Comments	Step-down procedure (starting with 30 mg vs. placebo) to identify the minimum effective dose. The step-down testing protects the type I error rate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.44
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment difference between "Degarelix 20 mg" and "Placebo" at Month 3.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 10 mg
	Comments	Analysis of Covariance (ANCOVA) of the change from baseline in IPSS at Month 3 in the FAS population using the Last Observation Carried Forward (LOCF) method, including the baseline IPSS as adjusting covariate and treatment group, prostate volume stratum (<30 mL and ≥30 mL), and region (North America and Europe) as factors.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2342
	Comments	P-value based on Williams' extended trend test of comparison vs. placebo at Month 3. No adjustment for multiple comparisons was made.
	Method	Step-down, Williams' extended trend test
	Comments	Step-down procedure (starting with 30 mg vs. placebo) to identify the minimum effective dose. The step-down testing protects the type I error rate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.92
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment difference between "Degarelix 10 mg" and "Placebo" at Month 3.

2. Secondary Outcome

Title	Mean Change in IPSS
Description	This secondary outcome measure was used to assess the maintained dose-response of the 3 degarelix dose groups in terms of severity of LUTS and progress of the disease process, versus the placebo group.
Time Frame	From Baseline to Month 4, Month 5 and Month 6 after Dosing

Outcome Measure Data

Analysis Population Description

FAS. The "as planned" patient allocation for treatment groups was used (please refer to the Baseline Characteristics section).

Arm/Group Title	Placebo	Degarelix 10 mg	Degarelix 20 mg	Degarelix 30 mg
Arm/Group Description	Mannitol 50 mg/mL solution. The dose was administered as a subcutaneous (s.c.) injection in the abdominal region.	Degarelix 10 mg: 10 mg degarelix, 40 mg/mL solution. The dose was administered as a s.c. injection in the abdominal region.	Degarelix 20 mg: 20 mg degarelix, 40 mg/mL solution. The dose was administered as a s.c. injection in the abdominal region.	Degarelix 30 mg: 30 mg degarelix, 40 mg/mL solution. The dose was administered as a s.c. injection in the abdominal region.
Measure Participants	100	101	100	102
Mean Percentage Change at Month 4	-4.12 (5.65)	-5.52 (6.18)	-6.3 (6.38)	-5.64 (5.6)
Mean Percentage Change at Month 5	-4.34 (5.94)	-5.59 (6.89)	-6.1 (6.46)	-5.37 (5.97)
Mean Percentage Change at Month 6	-4.3 (5.47)	-5.42 (6.7)	-5.72 (5.59)	-5.62 (5.69)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 30 mg
	Comments	ANCOVA of the change from baseline in IPSS at Months 4 in the FAS population using the LOCF method, including the baseline IPSS as adjusting covariate and treatment group, prostate volume stratum (<30 mL and ≥30 mL), and region (North America and Europe) as factors.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0367
	Comments	P-values based on Williams' extended trend test of comparison vs. placebo at Month 4. No adjustment for multiple comparisons was made.
	Method	Step-down, Williams' extended trend test
	Comments	Step-down procedure (starting with 30 mg vs. placebo) to identify the minimum effective dose. The step-down testing protects the type I error rate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.62
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment difference between "Degarelix 30 mg" and "Placebo" at Month 4.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 20 mg
	Comments	ANCOVA of the change from baseline in IPSS at Month 4 in the FAS population using the LOCF method, including the baseline IPSS as adjusting covariate and treatment group, prostate volume stratum (<30 mL and ≥30 mL), and region (North America and Europe) as factors.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0231
	Comments	P-value based on Williams' extended trend test of comparison vs. placebo at Month 4. No adjustment for multiple comparisons was made.
	Method	Step-down, Williams' extended trend test
	Comments	Step-down procedure (starting with 30 mg vs. placebo) to identify the minimum effective dose. The step-down testing protects the type I error rate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.97
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment difference between "Degarelix 20 mg" and "Placebo" at Month 4.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 10 mg
	Comments	ANCOVA of the change from baseline in IPSS at Month 4 in the FAS population using the LOCF method, including the baseline IPSS as adjusting covariate and treatment group, prostate volume stratum (<30 mL and ≥30 mL), and region (North America and Europe) as factors.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1638
	Comments	P-value based on Williams' extended trend test of comparison vs. placebo at Month 4. No adjustment for multiple comparisons was made.
	Method	Step-down, Williams' extended trend test
	Comments	Step-down procedure (starting with 30 mg vs. placebo) to identify the minimum effective dose. The step-down testing protects the type I error rate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.11
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment difference between "Degarelix 10 mg" and "Placebo" at Month 4.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 30 mg
	Comments	ANCOVA of the change from baseline in IPSS at Month 5 in the FAS population using the LOCF method, including the baseline IPSS as adjusting covariate and treatment group, prostate volume stratum (<30 mL and ≥30 mL), and region (North America and Europe) as factors.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1941
	Comments	P-values based on Williams' extended trend test of comparisons vs. placebo at Month 5. No adjustment for multiple comparison was made.
	Method	Step-down, Williams' extended trend test
	Comments	Step-down procedure (starting with 30 mg vs. placebo) to identify the minimum effective dose. The step-down testing protects the type I error rate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.14
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment difference between "Degarelix 30 mg" and "Placebo" at Month 5.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 20 mg
	Comments	ANCOVA of the change from baseline in IPSS at Month 5 in the FAS population using the LOCF method, including the baseline IPSS as adjusting covariate and treatment group, prostate volume stratum (<30 mL and ≥30 mL), and region (North America and Europe) as factors.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1083
	Comments	P-value based on Williams' extended trend test of comparison vs. placebo at Month 5. No adjustment for multiple comparisons was made.
	Method	Step-down, Williams' extended trend test
	Comments	Step-down procedure (starting with 30 mg vs. placebo) to identify the minimum effective dose. The step-down testing protects the type I error rate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.54
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment difference between "Degarelix 20 mg" and "Placebo" at Month 5.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 10 mg
	Comments	ANCOVA of the change from baseline in IPSS at Month 5 in the FAS population using the LOCF method, including the baseline IPSS as adjusting covariate and treatment group, prostate volume stratum (<30 mL and ≥30 mL), and region (North America and Europe) as factors.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2782
	Comments	P-value based on Williams' extended trend test of comparison vs. placebo at Month 5. No adjustment for multiple comparisons was made.
	Method	Step-down, Williams' extended trend test
	Comments	Step-down procedure (starting with 30 mg vs. placebo) to identify the minimum effective dose. The step-down testing protects the type I error rate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.95
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment difference between "Degarelix 10 mg" and "Placebo" at Month 5.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 30 mg
	Comments	ANCOVA of the change from baseline in IPSS at Month 6 in the FAS population using the LOCF method, including the baseline IPSS as adjusting covariate and treatment group, prostate volume stratum (<30 mL and ≥30 mL), and region (North America and Europe) as factors.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1562
	Comments	P-values based on Williams' extended trend test of comparison vs. placebo at Month 6. No adjustment for multiple comparisons was made.
	Method	Step-down, Williams' extended trend test
	Comments	Step-down procedure (starting with 30 mg vs. placebo) to identify the minimum effective dose. The step-down testing protects the type I error rate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.15
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment difference between "Degarelix 30 mg" and "Placebo" at Month 6.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 20 mg
	Comments	ANCOVA of the change from baseline in IPSS at Month 6 in the FAS population using the LOCF method, including the baseline IPSS as adjusting covariate and treatment group, prostate volume stratum (<30 mL and ≥30 mL), and region (North America and Europe) as factors.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1736
	Comments	P-value based on Williams' extended trend test of comparison vs. placebo at Month 6. No adjustment for multiple comparisons was made.
	Method	Step-down, Williams' extended trend test
	Comments	Step-down procedure (starting with 30 mg vs. placebo) to identify the minimum effective dose. The step-down testing protects the type I error rate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.24
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment difference between "Degarelix 20 mg" and "Placebo" at Month 6.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 10 mg
	Comments	ANCOVA of the change from baseline in IPSS at Month 6 in the FAS population using the LOCF method, including the baseline IPSS as adjusting covariate and treatment group, prostate volume stratum (<30 mL and ≥30 mL), and region (North America and Europe) as factors.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3132
	Comments	P-value based on Williams' extended trend test of comparison vs. placebo at Month 6. No adjustment for multiple comparisons was made.
	Method	Step-down, Williams' extended trend test
	Comments	Step-down procedure (starting with 30 mg vs. placebo) to identify the minimum effective dose. The step-down testing protects the type I error rate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.84
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment difference between "Degarelix 10 mg" and "Placebo" at Month 6.

3. Secondary Outcome

Title	Odds Ratio (as Compared to Placebo) of Treatment Response in IPSS
Description	A 3-point reduction in IPSS score compared to baseline is defined as a clinically meaningful treatment response. Percentage of participants who met criteria for a clinically meaningful treatment response and odds ratios of treatment responses between each degarelix dose group and the placebo group are presented.
Time Frame	At Month 3, Month 4, Month 5 and Month 6 after Dosing

Outcome Measure Data

Analysis Population Description

FAS. The "as planned" patient allocation for treatment groups was used (please refer to the Baseline Characteristics section).

Arm/Group Title	Placebo	Degarelix 10 mg	Degarelix 20 mg	Degarelix 30 mg
Arm/Group Description	Mannitol 50 mg/mL solution. The dose was administered as a subcutaneous (s.c.) injection in the abdominal region.	Degarelix 10 mg: 10 mg degarelix, 40 mg/mL solution. The dose was administered as a s.c. injection in the abdominal region.	Degarelix 20 mg: 20 mg degarelix, 40 mg/mL solution. The dose was administered as a s.c. injection in the abdominal region.	Degarelix 30 mg: 30 mg degarelix, 40 mg/mL solution. The dose was administered as a s.c. injection in the abdominal region.
Measure Participants	100	101	100	102
3-point reduction in IPSS vs. baseline (Month 3)	59.0 59%	72.3 71.6%	69.0 69%	68.6 67.3%
3-point reduction in IPSS vs. baseline (Month 4)	57.0 57%	65.3 64.7%	71.0 71%	70.6 69.2%
3-point reduction in IPSS vs. baseline (Month 5)	61.0 61%	64.4 63.8%	66.0 66%	67.6 66.3%
3-point reduction in IPSS vs. baseline (Month 6)	62.0 62%	68.3 67.6%	67.0 67%	71.6 70.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 30 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2034
	Comments	Adjustments were made for treatment group, baseline IPSS, graphical region (North America and Europe) and baseline prostate size (<30 mL and ≥30 mL). Unadjusted p-value of comparison vs. placebo at Month 3.
	Method	Regression, Logistic
	Comments	No adjustment for multiple comparisons was made. LOCF.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.46
	Confidence Interval	(2-Sided) 95%; 0.814 to 2.628
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds ratio of treatment response between "Degarelix 30 mg" and "Placebo" at Month 3.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 20 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1748
	Comments	Adjustments were made for treatment group, baseline IPSS, graphical region (North America and Europe) and baseline prostate size (<30 mL and ≥30 mL). Unadjusted p-value of comparison vs. placebo at Month 3.
	Method	Regression, Logistic
	Comments	No adjustment for multiple comparisons was made. LOCF.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.50
	Confidence Interval	(2-Sided) 95%; 0.834 to 2.710
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds ratio of treatment response between "Degarelix 20 mg" and "Placebo" at Month 3.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 10 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0658
	Comments	Adjustments were made for treatment group, baseline IPSS, graphical region (North America and Europe) and baseline prostate size (<30 mL and ≥30 mL). Unadjusted p-value of comparison vs. placebo at Month 3.
	Method	Regression, Logistic
	Comments	No adjustment for multiple comparisons was made. LOCF.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.75
	Confidence Interval	(2-Sided) 95%; 0.964 to 3.195
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds ratio of treatment response between "Degarelix 10 mg" and "Placebo" at Month 3.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 30 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0587
	Comments	Adjustments were made for treatment group, baseline IPSS, graphical region (North America and Europe) and baseline prostate size (<30 mL and ≥30 mL). Unadjusted p-value of comparison vs. placebo at Month 4.
	Method	Regression, Logistic
	Comments	No adjustment for multiple comparisons was made. LOCF.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.77
	Confidence Interval	(2-Sided) 95%; 0.979 to 3.184
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds ratio of treatment response between "Degarelix 30 mg" and "Placebo" at Month 4.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 20 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0490
	Comments	Adjustments were made for treatment group, baseline IPSS, graphical region (North America and Europe) and baseline prostate size (<30 mL and ≥30 mL). Unadjusted p-value of comparison vs. placebo at Month 4.
	Method	Regression, Logistic
	Comments	No adjustment for multiple comparisons was made. LOCF.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.81
	Confidence Interval	(2-Sided) 95%; 1.003 to 3.283
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds ratio of treatment response between "Degarelix 20 mg" and "Placebo" at Month 4.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 10 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2742
	Comments	Adjustments were made for treatment group, baseline IPSS, graphical region (North America and Europe) and baseline prostate size (<30 mL and ≥30 mL). Unadjusted p-value of comparison vs. placebo at Month 4.
	Method	Regression, Logistic
	Comments	No adjustment for multiple comparisons was made. LOCF.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.38
	Confidence Interval	(2-Sided) 95%; 0.774 to 2.464
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds ratio of treatment response between "Degarelix 10 mg" and "Placebo" at Month 4.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 30 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4206
	Comments	Adjustments were made for treatment group, baseline IPSS, graphical region (North America and Europe) and baseline prostate size (<30 mL and ≥30 mL). Unadjusted p-value of comparison vs. placebo at Month 5.
	Method	Regression, Logistic
	Comments	No adjustment for multiple comparisons was made. LOCF.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.28
	Confidence Interval	(2-Sided) 95%; 0.706 to 2.304
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds ratio of treatment response between "Degarelix 30 mg" and "Placebo" at Month 5.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 20 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5494
	Comments	Adjustments were made for treatment group, baseline IPSS, graphical region (North America and Europe) and baseline prostate size (<30 mL and ≥30 mL). Unadjusted p-value of comparison vs. placebo at Month 5.
	Method	Regression, Logistic
	Comments	No adjustment for multiple comparisons was made. LOCF.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.20
	Confidence Interval	(2-Sided) 95%; 0.664 to 2.160
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds ratio of treatment response between "Degarelix 20 mg" and "Placebo" at Month 5.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 10 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7586
	Comments	Adjustments were made for treatment group, baseline IPSS, graphical region (North America and Europe) and baseline prostate size (<30 mL and ≥30 mL). Unadjusted p-value of comparison vs. placebo at Month 5.
	Method	Regression, Logistic
	Comments	No adjustment for multiple comparisons was made. LOCF.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.10
	Confidence Interval	(2-Sided) 95%; 0.609 to 1.975
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds ratio of treatment response between "Degarelix 10 mg" and "Placebo" at Month 5.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 30 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1946
	Comments	Adjustments were made for treatment group, baseline IPSS, graphical region (North America and Europe) and baseline prostate size (<30 mL and ≥30 mL). Unadjusted p-value of comparison vs. placebo at Month 6.
	Method	Regression, Logistic
	Comments	No adjustment for multiple comparisons was made. LOCF.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.49
	Confidence Interval	(2-Sided) 95%; 0.816 to 2.717
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds ratio of treatment response between "Degarelix 30 mg" and "Placebo" at Month 6.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 20 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5380
	Comments	Adjustments were made for treatment group, baseline IPSS, graphical region (North America and Europe) and baseline prostate size (<30 mL and ≥30 mL). Unadjusted p-value of comparison vs. placebo at Month 6.
	Method	Regression, Logistic
	Comments	No adjustment for multiple comparisons was made. LOCF.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.20
	Confidence Interval	(2-Sided) 95%; 0.667 to 2.174
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds ratio of treatment response between "Degarelix 20 mg" and "Placebo" at Month 6.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 10 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4263
	Comments	Adjustments were made for treatment group, baseline IPSS, graphical region (North America and Europe) and baseline prostate size (<30 mL and ≥30 mL). Unadjusted p-value of comparison vs. placebo at Month 6.
	Method	Regression, Logistic
	Comments	No adjustment for multiple comparisons was made. LOCF.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.27
	Confidence Interval	(2-Sided) 95%; 0.702 to 2.308
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds ratio of treatment response between "Degarelix 10 mg" and "Placebo" at Month 6.

4. Secondary Outcome

Title	Mean Percentage Change in Total Prostate Volume (TPV)
Description	TPV was measured directly by standardised trans-rectal ultrasound (TRUS).
Time Frame	From Baseline to Month 3 and Month 6 after Dosing

Outcome Measure Data

Analysis Population Description

FAS. The "as planned" patient allocation for treatment groups was used (please refer to the Baseline Characteristics section).

Arm/Group Title	Placebo	Degarelix 10 mg	Degarelix 20 mg	Degarelix 30 mg
Arm/Group Description	Mannitol 50 mg/mL solution. The dose was administered as a subcutaneous (s.c.) injection in the abdominal region.	Degarelix 10 mg: 10 mg degarelix, 40 mg/mL solution. The dose was administered as a s.c. injection in the abdominal region.	Degarelix 20 mg: 20 mg degarelix, 40 mg/mL solution. The dose was administered as a s.c. injection in the abdominal region.	Degarelix 30 mg: 30 mg degarelix, 40 mg/mL solution. The dose was administered as a s.c. injection in the abdominal region.
Measure Participants	100	101	100	102
Mean Percentage Change at Month 3	3.15 (23.3)	-1.46 (32.7)	-0.252 (24.5)	0.188 (24.4)
Mean Percentage Change at Month 6	3.96 (29.3)	1.57 (31)	2.35 (26.5)	-0.0112 (20.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 30 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4607
	Comments	No adjustment for multiple comparisons was made. Unadjusted p-value of comparison vs. placebo at Month 3.
	Method	ANCOVA
	Comments	ANCOVA with baseline TPV as covariate and treatment group, region (North America,Europe) and prostate volume stratum (<30 mL,≥30 mL) as factors. LOCF.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.76
	Confidence Interval	(2-Sided) 95%; -10.113 to 4.590
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment difference between "Degarelix 30 mg" and "Placebo" at Month 3.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 20 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3876
	Comments	No adjustment for multiple comparisons was made. Unadjusted p-value of comparison vs. placebo at Month 3.
	Method	ANCOVA
	Comments	ANCOVA with baseline TPV as covariate and treatment group, region (North America,Europe) and prostate volume stratum (<30 mL,≥30 mL) as factors. LOCF.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.24
	Confidence Interval	(2-Sided) 95%; -10.614 to 4.128
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment difference between "Degarelix 20 mg" and "Placebo" at Month 3.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 10 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2548
	Comments	No adjustment for multiple comparisons was made. Unadjusted p-value of comparison vs. placebo at Month 3.
	Method	ANCOVA
	Comments	ANCOVA with baseline TPV as covariate and treatment group, region (North America,Europe) and prostate volume stratum (<30 mL,≥30 mL) as factors. LOCF.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.28
	Confidence Interval	(2-Sided) 95%; -11.650 to 3.096
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment difference between "Degarelix 10 mg" and "Placebo" at Month 3.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 30 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5652
	Comments	No adjustment for multiple comparisons was made. Unadjusted p-value of comparison vs. placebo at Month 6.
	Method	ANCOVA
	Comments	ANCOVA with baseline TPV as covariate and treatment group, region (North America,Europe) and prostate volume stratum (<30 mL,≥30 mL) as factors. LOCF.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.20
	Confidence Interval	(2-Sided) 95%; -9.729 to 5.322
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment difference between "Degarelix 30 mg" and "Placebo" at Month 6.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 20 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7502
	Comments	No adjustment for multiple comparisons was made. Unadjusted p-value of comparison vs. placebo at Month 6.
	Method	ANCOVA
	Comments	ANCOVA with baseline TPV as covariate and treatment group, region (North America,Europe) and prostate volume stratum (<30 mL,≥30 mL) as factors. LOCF.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.22
	Confidence Interval	(2-Sided) 95%; -8.768 to 6.322
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment difference between "Degarelix 20 mg" and "Placebo" at Month 6.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 10 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6089
	Comments	No adjustment for multiple comparisons was made. Unadjusted p-value of comparison vs. placebo at Month 6.
	Method	ANCOVA
	Comments	ANCOVA with baseline TPV as covariate and treatment group, region (North America,Europe) and prostate volume stratum (<30 mL,≥30 mL) as factors. LOCF.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.97
	Confidence Interval	(2-Sided) 95%; -9.513 to 5.581
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment difference between "Degarelix 10 mg" and "Placebo" at Month 6.

5. Secondary Outcome

Title	Mean Change in Maximum Urinary Flow (Qmax)
Description	Urinary flow rate (mL/second) was measured using uroflowmetry performed according to the recommendation from the International Continence Society (ICS).
Time Frame	From Baseline to Month 3 and Month 6 after Dosing

Outcome Measure Data

Analysis Population Description

FAS. The "as planned" patient allocation for treatment groups was used (please refer to the Baseline Characteristics section).

Arm/Group Title	Placebo	Degarelix 10 mg	Degarelix 20 mg	Degarelix 30 mg
Arm/Group Description	Mannitol 50 mg/mL solution. The dose was administered as a subcutaneous (s.c.) injection in the abdominal region.	Degarelix 10 mg: 10 mg degarelix, 40 mg/mL solution. The dose was administered as a s.c. injection in the abdominal region.	Degarelix 20 mg: 20 mg degarelix, 40 mg/mL solution. The dose was administered as a s.c. injection in the abdominal region.	Degarelix 30 mg: 30 mg degarelix, 40 mg/mL solution. The dose was administered as a s.c. injection in the abdominal region.
Measure Participants	100	101	100	102
Mean Percentage Change at Month 3	0.652 (3.8)	0.564 (5.08)	0.626 (5.68)	0.723 (3.91)
Mean Percentage Change at Month 6	1.04 (5.34)	0.516 (4.85)	0.582 (5.43)	1.43 (5.29)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 30 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8511
	Comments	No adjustment for multiple comparisons was made. Unadjusted p-value of comparison vs. placebo at Month 3.
	Method	ANCOVA
	Comments	ANCOVA with baseline Qmax as covariate and treatment group, region (North America,Europe) and prostate volume stratum (<30 mL,≥30 mL) as factors.LOCF.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.11
	Confidence Interval	(2-Sided) 95%; -1.068 to 1.294
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment difference between "Degarelix 30 mg" and "Placebo" at Month 3.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 20 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6331
	Comments	No adjustment for multiple comparisons was made. Unadjusted p-value of comparison vs. placebo at Month 3.
	Method	ANCOVA
	Comments	ANCOVA with baseline Qmax as covariate and treatment group, region (North America,Europe) and prostate volume stratum (<30 mL,≥30 mL) as factors.LOCF.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.29
	Confidence Interval	(2-Sided) 95%; -0.900 to 1.477
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment difference between "Degarelix 20 mg" and "Placebo" at Month 3.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 10 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9090
	Comments	No adjustment for multiple comparisons was made. Unadjusted p-value of comparison vs. placebo at Month 3.
	Method	ANCOVA
	Comments	ANCOVA with baseline Qmax as covariate and treatment group, region (North America,Europe) and prostate volume stratum (<30 mL,≥30 mL) as factors.LOCF.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.07
	Confidence Interval	(2-Sided) 95%; -1.113 to 1.250
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment difference between "Degarelix 10 mg" and "Placebo" at Month 3.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 30 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5469
	Comments	No adjustment for multiple comparisons was made. Unadjusted p-value of comparison vs. placebo at Month 6.
	Method	ANCOVA
	Comments	ANCOVA with baseline Qmax as covariate and treatment group, region (North America,Europe) and prostate volume stratum (<30 mL,≥30 mL) as factors.LOCF.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.42
	Confidence Interval	(2-Sided) 95%; -0.956 to 1.802
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment difference between "Degarelix 30 mg" and "Placebo" at Month 6.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 20 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7906
	Comments	No adjustment for multiple comparisons was made. Unadjusted p-value of comparison vs. placebo at Month 6.
	Method	ANCOVA
	Comments	ANCOVA with baseline Qmax as covariate and treatment group, region (North America,Europe) and prostate volume stratum (<30 mL,≥30 mL) as factors.LOCF.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.19
	Confidence Interval	(2-Sided) 95%; -1.576 to 1.200
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment difference between "Degarelix 20 mg" and "Placebo" at Month 6.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Degarelix 10 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5757
	Comments	No adjustment for multiple comparisons was made. Unadjusted p-value of comparison vs. placebo at Month 6.
	Method	ANCOVA
	Comments	ANCOVA with baseline Qmax as covariate and treatment group, region (North America,Europe) and prostate volume stratum (<30 mL,≥30 mL) as factors.LOCF.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.39
	Confidence Interval	(2-Sided) 95%; -1.773 to 0.987
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment difference between "Degarelix 10 mg" and "Placebo" at Month 6.

Adverse Events

Time Frame	This was a single dose trial and adverse events were recorded from signed informed consent up to a maximum of 12 months after the dose. However, the trial was stopped when all patients had completed the visit scheduled 6 months after the dosing.
Adverse Event Reporting Description	Adverse events were evaluated at each visit. The safety analyses were based on the actual treatment. Three patients did not receive their randomised treatment: 2 patients randomised to placebo received 30 mg, and 1 patient randomised to 20 mg received 30 mg degarelix. They were included in the actual treatment group in the safety analysis set.
Arm/Group Title	Placebo		Degarelix 10 mg		Degarelix 20 mg		Degarelix 30 mg
Arm/Group Description	Placebo: Mannitol 50 mg/mL solution. The dose was administered as a s.c. injection in the abdominal region.		Degarelix 10 mg: 10 mg degarelix, 40 mg/mL solution. The dose was administered as a s.c. injection in the abdominal region.		Degarelix 20 mg: 20 mg degarelix, 40 mg/mL solution. The dose was administered as a s.c. injection in the abdominal region.		Degarelix 30 mg: 30 mg degarelix, 40 mg/mL solution. The dose was administered as a s.c. injection in the abdominal region.
All Cause Mortality
	Placebo		Degarelix 10 mg		Degarelix 20 mg		Degarelix 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Degarelix 10 mg		Degarelix 20 mg		Degarelix 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/98 (2%)		8/101 (7.9%)		2/100 (2%)		7/105 (6.7%)
Cardiac disorders
Angina pectoris	1/98 (1%)	1	0/101 (0%)	0	0/100 (0%)	0	0/105 (0%)	0
Atrioventricular block complete	0/98 (0%)	0	0/101 (0%)	0	0/100 (0%)	0	1/105 (1%)	1
Sick sinus syndrome	0/98 (0%)	0	1/101 (1%)	1	0/100 (0%)	0	0/105 (0%)	0
Gastrointestinal disorders
Abdominal pain upper	1/98 (1%)	1	0/101 (0%)	0	0/100 (0%)	0	0/105 (0%)	0
Ileus	0/98 (0%)	0	1/101 (1%)	1	0/100 (0%)	0	0/105 (0%)	0
Subileus	0/98 (0%)	0	1/101 (1%)	1	0/100 (0%)	0	0/105 (0%)	0
Infections and infestations
Abscess intestinal	0/98 (0%)	0	1/101 (1%)	1	0/100 (0%)	0	0/105 (0%)	0
Clostridium difficile colitis	0/98 (0%)	0	0/101 (0%)	0	1/100 (1%)	1	0/105 (0%)	0
Injury, poisoning and procedural complications
Contusion	0/98 (0%)	0	1/101 (1%)	1	0/100 (0%)	0	0/105 (0%)	0
Investigations
Coagulation time prolonged	1/98 (1%)	1	0/101 (0%)	0	0/100 (0%)	0	0/105 (0%)	0
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	0/98 (0%)	0	0/101 (0%)	0	1/100 (1%)	1	1/105 (1%)	1
Osteoarthritis	0/98 (0%)	0	1/101 (1%)	1	0/100 (0%)	0	1/105 (1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenosquamous cell carcinoma	0/98 (0%)	0	1/101 (1%)	1	0/100 (0%)	0	0/105 (0%)	0
Colon cancer metastatic	0/98 (0%)	0	0/101 (0%)	0	0/100 (0%)	0	1/105 (1%)	1
Prostate cancer	0/98 (0%)	0	1/101 (1%)	1	0/100 (0%)	0	0/105 (0%)	0
Nervous system disorders
Carotid sinus syndrome	0/98 (0%)	0	1/101 (1%)	1	0/100 (0%)	0	0/105 (0%)	0
Cerebrovascular accident	0/98 (0%)	0	1/101 (1%)	1	0/100 (0%)	0	0/105 (0%)	0
Psychiatric disorders
Depression	0/98 (0%)	0	0/101 (0%)	0	0/100 (0%)	0	1/105 (1%)	1
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/98 (0%)	0	0/101 (0%)	0	0/100 (0%)	0	1/105 (1%)	1
Nasal septum deviation	1/98 (1%)	1	0/101 (0%)	0	0/100 (0%)	0	0/105 (0%)	0
Pulmonary embolism	0/98 (0%)	0	1/101 (1%)	1	0/100 (0%)	0	0/105 (0%)	0
Respiratory failure	0/98 (0%)	0	1/101 (1%)	1	0/100 (0%)	0	0/105 (0%)	0
Vascular disorders
Deep vein thrombosis	0/98 (0%)	0	1/101 (1%)	1	0/100 (0%)	0	0/105 (0%)	0
Hypertension	0/98 (0%)	0	0/101 (0%)	0	0/100 (0%)	0	1/105 (1%)	1
Other (Not Including Serious) Adverse Events
	Placebo		Degarelix 10 mg		Degarelix 20 mg		Degarelix 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/98 (31.6%)		35/101 (34.7%)		39/100 (39%)		56/105 (53.3%)
General disorders
Injection site erythema	0/98 (0%)	0	11/101 (10.9%)	11	14/100 (14%)	14	18/105 (17.1%)	18
Injection site pain	0/98 (0%)	0	2/101 (2%)	2	10/100 (10%)	10	18/105 (17.1%)	19
Injection site induration	0/98 (0%)	0	6/101 (5.9%)	6	7/100 (7%)	7	11/105 (10.5%)	11
Infections and infestations
Nasopharyngitis	5/98 (5.1%)	5	7/101 (6.9%)	8	2/100 (2%)	2	5/105 (4.8%)	5
Influenza	5/98 (5.1%)	5	5/101 (5%)	5	3/100 (3%)	3	5/105 (4.8%)	5
Investigations
Prostatic specific antigen increased	6/98 (6.1%)	6	4/101 (4%)	4	5/100 (5%)	6	6/105 (5.7%)	6
Musculoskeletal and connective tissue disorders
Back pain	9/98 (9.2%)	9	5/101 (5%)	5	5/100 (5%)	5	5/105 (4.8%)	6
Nervous system disorders
Headache	5/98 (5.1%)	5	3/101 (3%)	3	3/100 (3%)	3	3/105 (2.9%)	3
Respiratory, thoracic and mediastinal disorders
Cough	5/98 (5.1%)	5	3/101 (3%)	3	1/100 (1%)	1	2/105 (1.9%)	2
Vascular disorders
Hypertension	7/98 (7.1%)	8	6/101 (5.9%)	6	4/100 (4%)	5	9/105 (8.6%)	10
Hot flush	1/98 (1%)	2	1/101 (1%)	1	4/100 (4%)	4	8/105 (7.6%)	10

Limitations/Caveats

Following the planned 6-month interim analysis when all patients had completed the visit scheduled 6 months after dosing, a decision was taken to stop the trial since the primary efficacy endpoint was not met.

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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.