Prostate Cancer Study In Men Who Have Failed First-Line Androgen Deprivation Therapy

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00470834
• Collaborator: (none)
• Enrollment: 127
• Locations: 62
• Arms: 2
• Duration (Months): 69.1
• Patients Per Site: 2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Dutasteride inhibits the conversion of testosterone to dihydrotestosterone (DHT) the male hormone that leads to benign prostate growth. By blocking the conversion of testosterone to DHT, dutasteride could allow bicalutamide to be a more effective anti-androgen thus prolonging bicalutamide's efficacy.

Condition or Disease	Intervention/Treatment	Phase
Neoplasms, Prostate	Drug: dutasteride; Drug: placebo; Drug: bicalutamide	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 127 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized Double-Blind Parallel Group Study Comparing Casodex (or Generic Equivalent) 50mg Plus Placebo to Casodex (or Generic Equivalent) 50mg Plus Dutasteride 3.5mg Administered for 18 Months to Men With Prostate Cancer Who Have Failed First-Line Androgen Deprivation Therapy (Assessed by Rising PSA) Followed by a Two-Year Extension Phase
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: Feb 1, 2013
• Actual Study Completion Date: Feb 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 50 mg bicalutamide and 3.5 mg Dutasteride (IP)	Drug: dutasteride; 0.5mg dutasteride (Investigation Product); Drug: bicalutamide; 50 mg Casodex or generic equivalent
Placebo Comparator: Arm 2 50 mg bicalutamide and placebo	Drug: placebo; making placebo; Drug: bicalutamide; 50 mg Casodex or generic equivalent

Outcome Measures

Primary Outcome Measures

1. Time to Disease Progression [Interval of time between the date of the start of treatment and the date of disease progression (up to Study Month 42)]

   Time to disease progression (PD) is defined as the interval of time between the date of the start of treatment and the date of PD. PD is defined as prostate specific antigen (PSA) progression from Baseline (PSA value is 25% and at least 2 nanograms per milliliter [ng/mL] above Baseline, confirmed by a second PSA value); PSA progression from nadir, without a 50% decrease from Baseline (PSA value is 25% and at least 2 ng/mL above nadir, confirmed by a second PSA value); PSA progression from nadir, with a 50% or more decrease from Baseline (PSA value is 50% and at least 2 ng/mL above nadir, confirmed by a second PSA value); metastatic disease (radiographic evidence of metastatic disease); death due to prostate cancer; or the receipt of post-Baseline rescue medication. PSA confirmation was not required if no subsequent PSA values were available. Participants who did not experience an event were censored at the date of the latest follow-up information.

Secondary Outcome Measures

1. Time to Treatment Failure [Interval of time between the date of the start of treatment and the date of treatment failure (up to Study Month 42)]

   Time to treatment failure is defined as the interval of time between the date of the start of treatment and the date of treatment failure. Treatment failure is defined as PSA progression from Baseline (PSA value is 25% and at least 2 ng/mL above Baseline, confirmed by a second PSA value); metastatic disease (radiographic evidence of metastatic disease); death due to prostate cancer; or receipt of post-baseline rescue medications. PSA confirmation was not required if no subsequent PSA values were available. Participants who did not experience an event were censored at the date of the latest follow-up information.

2. Number of Participants With PSA Response [Time from Baseline PSA measurement until the first PSA measurement with a 50% or greater reduction in PSA values (up to Study Month 42)]

   PSA response is defined as a 50% or greater decrease in PSA from Baseline, confirmed by a second PSA measurement. The time of this response was the date of the first PSA measurement that showed a 50% or greater decrease from the Baseline PSA measurement. PSA confirmation was not required if no subsequent PSA values were available.

3. Change From Baseline in Total PSA at Months 6, 12, 18, 21, and 42 [Baseline and Months 6, 12, 18, 21, and 42]

   Change from Baseline in total PSA was measured at each scheduled post-baseline visit using a general linear model with effects for treatment and Baseline total PSA. Analysis was done using the last observation carried forward (LOCF) approach, in which missing post-Baseline values were imputed with earlier non-missing values. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

4. Number of Participants With Metastatic Disease [Interval of time between the date of the start of treatment and the date of radiographic evidence of metastatic disease (up to Study Month 42)]

   Metastatic disease is that evidenced by a radiographic assessment. The time of metastatic disease was the date of radiographic evidence.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 90 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Men ≥40 and ≤90 years of age

• Must have asymptomatic prostate cancer that has progressed during androgen deprivation therapy (rising PSA). PSA progression must have occurred after first-line treatment with GnRH analogues ( e.g. leuprolide, goserelin) or orchiectomy. PSA progression is defined by three rises in PSA each measured at least 4 weeks apart within the previous year.

• Serum PSA ≥2 and ≤20ng/ml from central laboratory. One PSA retest from central laboratory is allowed if the value is <2 or >20ng/ml; or if the PSA value is not consistent with the previous rising PSA values that determined progression while on a GnRH analogue.

• Serum Testosterone <50ng/ml from central laboratory.

• Non-metastatic prostate cancer as confirmed on prior bone scan performed within 8 weeks of screening.

• Expected survival ≥ 2 years

• ECOG Performance status 0, 1, or 2

Exclusion criteria:

• Additional hormonal therapy (excluding the current use of a GnRH analogue) within the past 6 months of:

• Estrogens (e.g. megestrol, medroxyprogesterone, cyproterone, DES)

• Drugs with antiandrogenic properties (e.g., spironolactone if >50mg/day, flutamide, bicalutamide*, ketoconazole**, progestational agents)

*The use of an antiandrogen during GnRH analogue induction for <6 weeks is acceptable, but none within the 3 months prior to study entry.

**The use of topical ketoconazole is permitted prior to and during the study. NOTE: Use of dietary and herbal supplements (e.g., selenium, Vitamin E, saw palmetto), excluding daily vitamins, during the study is discouraged, but not prohibited. All dietary and herbal supplement usage will be recorded in the eCRF.

• Treatment with oral glucocorticoids during the 3 months prior to randomization or expectation of their use during the study.

• Prior chemotherapy for prostate cancer. (prior prostatectomy or radiotherapy to the prostate are allowed)

• Prostate surgery including TUNA, TURP, TUIP, laser treatment, thermotherapy, balloon dilatation, prosthesis, and cryosurgical ablation within 2 months prior to enrollment.

• Current and/or previous use of the following medications:

• Finasteride (Proscar, Propecia), or Dutasteride (GI198745, AVODART) exposure within 6 months prior to study entry

• Anabolic steroids (within 6 months prior to study entry)

• Participation in any investigational or marketed drug trial within the 30 days prior to the first dose of study drug or anytime during the study period.

• Any unstable serious co-existing medical condition(s) including but not limited to myocardial infarction, coronary bypass surgery, unstable angina, cardiac arrhythmias, clinically evident congestive heart failure, or cerebrovascular accident within 6 months prior to Screening visit; uncontrolled diabetes; or peptic ulcer disease which is uncontrolled by medical management.

• Abnormal liver function test greater than 1.5 times the upper limit of normal for alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP] or bilirubin.

• Serum creatinine >2.0 times the upper limit of normal.

• History of another malignancy within five years that could affect the treatment of prostate cancer or survival of the subject.

• History or current evidence of drug or alcohol abuse within the last 12 months.

• History of any illness (including psychiatric) that, in the opinion of the investigator, might confound the results of the study or pose additional risk to the subject.

• Known hypersensitivity to any 5 alpha-reductase inhibitor or to any drug chemically related to dutasteride.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Homewood	Alabama	United States	35209
2	GSK Investigational Site	Huntsville	Alabama	United States	35801
3	GSK Investigational Site	Little Rock	Arkansas	United States	72205
4	GSK Investigational Site	Anaheim	California	United States	92801
5	GSK Investigational Site	Fresno	California	United States	93720
6	GSK Investigational Site	San Bernardino	California	United States	92404
7	GSK Investigational Site	San Diego	California	United States	92101
8	GSK Investigational Site	Denver	Colorado	United States	80211
9	GSK Investigational Site	Washington	District of Columbia	United States	20307
10	GSK Investigational Site	Aventura	Florida	United States	33180
11	GSK Investigational Site	Daytona Beach	Florida	United States	32114
12	GSK Investigational Site	Orlando	Florida	United States	32803
13	GSK Investigational Site	Galesburg	Illinois	United States	61401
14	GSK Investigational Site	Evansville	Indiana	United States	47713
15	GSK Investigational Site	Fort Wayne	Indiana	United States	46825
16	GSK Investigational Site	Jeffersonville	Indiana	United States	47130
17	GSK Investigational Site	Overland Park	Kansas	United States	66211
18	GSK Investigational Site	New Orleans	Louisiana	United States	70112
19	GSK Investigational Site	Shreveport	Louisiana	United States	71106
20	GSK Investigational Site	Annapolis	Maryland	United States	21401
21	GSK Investigational Site	Watertown	Massachusetts	United States	02472
22	GSK Investigational Site	Chaska	Minnesota	United States	55318
23	GSK Investigational Site	Minneapolis	Minnesota	United States	55455
24	GSK Investigational Site	St. Louis	Missouri	United States	63136
25	GSK Investigational Site	Omaha	Nebraska	United States	68114
26	GSK Investigational Site	Las Vegas	Nevada	United States	89148
27	GSK Investigational Site	Albany	New York	United States	12208
28	GSK Investigational Site	Garden City	New York	United States	11530
29	GSK Investigational Site	Manhasset	New York	United States	11030
30	GSK Investigational Site	New York	New York	United States	10016
31	GSK Investigational Site	Syracuse	New York	United States	13210
32	GSK Investigational Site	Concord	North Carolina	United States	28025
33	GSK Investigational Site	Columbus	Ohio	United States	43214
34	GSK Investigational Site	Bala Cynwyd	Pennsylvania	United States	19004
35	GSK Investigational Site	Lancaster	Pennsylvania	United States	17604
36	GSK Investigational Site	Philadelphia	Pennsylvania	United States	19107
37	GSK Investigational Site	Myrtle Beach	South Carolina	United States	29572
38	GSK Investigational Site	Memphis	Tennessee	United States	38119
39	GSK Investigational Site	Houston	Texas	United States	77074
40	GSK Investigational Site	San Antonio	Texas	United States	78229
41	GSK Investigational Site	Norfork	Virginia	United States	23502
42	GSK Investigational Site	Richmond	Virginia	United States	23235
43	GSK Investigational Site	Virginia Beach	Virginia	United States	23454
44	GSK Investigational Site	Williamsburg	Virginia	United States	23185
45	GSK Investigational Site	Seattle	Washington	United States	98166
46	GSK Investigational Site	Seattle	Washington	United States	98195-6015
47	GSK Investigational Site	Milwaukee	Wisconsin	United States	53226
48	GSK Investigational Site	Calgary	Alberta	Canada	T2V 1P9
49	GSK Investigational Site	Surrey	British Columbia	Canada	V3V 1N1
50	GSK Investigational Site	Victoria	British Columbia	Canada	V8T 5G1
51	GSK Investigational Site	Barrie	Ontario	Canada	L4M 7G1
52	GSK Investigational Site	Burlington	Ontario	Canada	L7S 1V2
53	GSK Investigational Site	North Bay	Ontario	Canada	P1B 7K8
54	GSK Investigational Site	Oakville	Ontario	Canada	L6H 3P1
55	GSK Investigational Site	Scarborough	Ontario	Canada	M1S 4V5
56	GSK Investigational Site	Sudbury	Ontario	Canada	P3E 4T3
57	GSK Investigational Site	Toronto	Ontario	Canada	M2K 2W1
58	GSK Investigational Site	Toronto	Ontario	Canada	M4C 5T2
59	GSK Investigational Site	Greenfield Park	Quebec	Canada	J4V 2H3
60	GSK Investigational Site	Laval	Quebec	Canada	H7G 2E6
61	GSK Investigational Site	Pointe-Claire	Quebec	Canada	H9R 4S3
62	GSK Investigational Site	Quebec		Canada	G1R 2J6

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00470834
• Other Study ID Numbers: AVO108943
• First Posted: May 8, 2007
• Last Update Posted: Feb 27, 2017
• Last Verified: Nov 1, 2016

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: prostate cancer; androgen deprivation therapy
• Additional relevant MeSH terms: Prostatic Neoplasms; Bicalutamide; Dutasteride

Study Results

Participant Flow

Arm/Group Title	Bicalutamide 50 mg/Placebo	Bicalutamide 50 mg/Dutasteride 3.5 mg
Arm/Group Description	Participants were randomly assigned to receive oral bicalutamide 50 milligrams (mg) and matching placebo once daily for 18 months. Participants who completed the 18-month treatment period with either stabilization or a positive response to their prostate cancer were offered participation in the 2-year extension phase , during which they would remain on their current treatment. A safety follow-up was conducted 16 weeks (+/-7 days) after withdrawal from investigational product (end of treatment or early withdrawal).	Participants were randomly assigned to receive oral bicalutamide 50 mg and dutasteride 3.5 mg once daily for 18 months. Participants who completed the 18-month treatment period with either stabilization or a positive response to their prostate cancer were offered participation in the 2-year extension phase, during which they would remain on their current treatment. A safety follow-up was conducted 16 weeks (+/-7 days) after withdrawal from investigational product (end of treatment or early withdrawal).
Period Title: Treatment Period (18 Months)
STARTED	65	62
COMPLETED	27	31
NOT COMPLETED	38	31
Period Title: Treatment Period (18 Months)
STARTED	26	30
COMPLETED	11	7
NOT COMPLETED	15	23

Baseline Characteristics

Arm/Group Title	Bicalutamide 50 mg/Placebo	Bicalutamide 50 mg/Dutasteride 3.5 mg	Total
Arm/Group Description	Participants were randomly assigned to receive oral bicalutamide 50 milligrams (mg) and matching placebo once daily for 18 months. Participants who completed the 18-month treatment period with either stabilization or a positive response to their prostate cancer were offered participation in the 2-year extension phase , during which they would remain on their current treatment. A safety follow-up was conducted 16 weeks (+/-7 days) after withdrawal from investigational product (end of treatment or early withdrawal).	Participants were randomly assigned to receive oral bicalutamide 50 mg and dutasteride 3.5 mg once daily for 18 months. Participants who completed the 18-month treatment period with either stabilization or a positive response to their prostate cancer were offered participation in the 2-year extension phase, during which they would remain on their current treatment. A safety follow-up was conducted 16 weeks (+/-7 days) after withdrawal from investigational product (end of treatment or early withdrawal).	Total of all reporting groups
Overall Participants	65	62	127
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	77.6 (7.90)	78.9 (5.94)	78.3 (7.02)
Gender (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	65 100%	62 100%	127 100%
Race/Ethnicity, Customized (participants) [Number]
African American/African Heritage	11 16.9%	10 16.1%	21 16.5%
American Indian or Alaska Native	2 3.1%	1 1.6%	3 2.4%
Asian-Japanese Heritage	1 1.5%	0 0%	1 0.8%
Asian-South East Asian Heritage	0 0%	1 1.6%	1 0.8%
White-White/Caucasian/European Heritage	51 78.5%	50 80.6%	101 79.5%

Outcome Measures

1. Primary Outcome

Title	Time to Disease Progression
Description	Time to disease progression (PD) is defined as the interval of time between the date of the start of treatment and the date of PD. PD is defined as prostate specific antigen (PSA) progression from Baseline (PSA value is 25% and at least 2 nanograms per milliliter [ng/mL] above Baseline, confirmed by a second PSA value); PSA progression from nadir, without a 50% decrease from Baseline (PSA value is 25% and at least 2 ng/mL above nadir, confirmed by a second PSA value); PSA progression from nadir, with a 50% or more decrease from Baseline (PSA value is 50% and at least 2 ng/mL above nadir, confirmed by a second PSA value); metastatic disease (radiographic evidence of metastatic disease); death due to prostate cancer; or the receipt of post-Baseline rescue medication. PSA confirmation was not required if no subsequent PSA values were available. Participants who did not experience an event were censored at the date of the latest follow-up information.
Time Frame	Interval of time between the date of the start of treatment and the date of disease progression (up to Study Month 42)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all participants randomized to study treatment. Data were not summarized for censored participants (no disease progression).

Arm/Group Title	Bicalutamide 50 mg/Placebo	Bicalutamide 50 mg/Dutasteride 3.5 mg
Arm/Group Description	Participants were randomly assigned to receive oral bicalutamide 50 milligrams (mg) and matching placebo once daily for 18 months. Participants who completed the 18-month treatment period with either stabilization or a positive response to their prostate cancer were offered participation in the 2-year extension phase , during which they would remain on their current treatment. A safety follow-up was conducted 16 weeks (+/-7 days) after withdrawal from investigational product (end of treatment or early withdrawal).	Participants were randomly assigned to receive oral bicalutamide 50 mg and dutasteride 3.5 mg once daily for 18 months. Participants who completed the 18-month treatment period with either stabilization or a positive response to their prostate cancer were offered participation in the 2-year extension phase, during which they would remain on their current treatment. A safety follow-up was conducted 16 weeks (+/-7 days) after withdrawal from investigational product (end of treatment or early withdrawal).
Measure Participants	41	40
Mean (Standard Deviation) [Days]	376.9 (333.94)	433.1 (324.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bicalutamide 50 mg/Placebo, Bicalutamide 50 mg/Dutasteride 3.5 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.79
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bicalutamide 50 mg/Placebo, Bicalutamide 50 mg/Dutasteride 3.5 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95%; 0.61 to 1.46
	Parameter Dispersion	Type: Value:
	Estimation Comments	The hazard ratio is based on the Cox proportional hazards model.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Bicalutamide 50 mg/Placebo, Bicalutamide 50 mg/Dutasteride 3.5 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative Risk Reduction
	Estimated Value	5.62
	Confidence Interval	(2-Sided) 95%; -46.14 to 39.05
	Parameter Dispersion	Type: Value:
	Estimation Comments	Relative Risk Reduction = 100 * (1 - Relative Risk).

2. Secondary Outcome

Title	Time to Treatment Failure
Description	Time to treatment failure is defined as the interval of time between the date of the start of treatment and the date of treatment failure. Treatment failure is defined as PSA progression from Baseline (PSA value is 25% and at least 2 ng/mL above Baseline, confirmed by a second PSA value); metastatic disease (radiographic evidence of metastatic disease); death due to prostate cancer; or receipt of post-baseline rescue medications. PSA confirmation was not required if no subsequent PSA values were available. Participants who did not experience an event were censored at the date of the latest follow-up information.
Time Frame	Interval of time between the date of the start of treatment and the date of treatment failure (up to Study Month 42)

Outcome Measure Data

Analysis Population Description

ITT Population. Data were not summarized for censored participants (no treatment failure).

Arm/Group Title	Bicalutamide 50 mg/Placebo	Bicalutamide 50 mg/Dutasteride 3.5 mg
Arm/Group Description	Participants were randomly assigned to receive oral bicalutamide 50 milligrams (mg) and matching placebo once daily for 18 months. Participants who completed the 18-month treatment period with either stabilization or a positive response to their prostate cancer were offered participation in the 2-year extension phase , during which they would remain on their current treatment. A safety follow-up was conducted 16 weeks (+/-7 days) after withdrawal from investigational product (end of treatment or early withdrawal).	Participants were randomly assigned to receive oral bicalutamide 50 mg and dutasteride 3.5 mg once daily for 18 months. Participants who completed the 18-month treatment period with either stabilization or a positive response to their prostate cancer were offered participation in the 2-year extension phase, during which they would remain on their current treatment. A safety follow-up was conducted 16 weeks (+/-7 days) after withdrawal from investigational product (end of treatment or early withdrawal).
Measure Participants	31	28
Mean (Standard Deviation) [Days]	368.4 (323.94)	457.5 (322.01)

3. Secondary Outcome

Title	Number of Participants With PSA Response
Description	PSA response is defined as a 50% or greater decrease in PSA from Baseline, confirmed by a second PSA measurement. The time of this response was the date of the first PSA measurement that showed a 50% or greater decrease from the Baseline PSA measurement. PSA confirmation was not required if no subsequent PSA values were available.
Time Frame	Time from Baseline PSA measurement until the first PSA measurement with a 50% or greater reduction in PSA values (up to Study Month 42)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Bicalutamide 50 mg/Placebo	Bicalutamide 50 mg/Dutasteride 3.5 mg
Arm/Group Description	Participants were randomly assigned to receive oral bicalutamide 50 milligrams (mg) and matching placebo once daily for 18 months. Participants who completed the 18-month treatment period with either stabilization or a positive response to their prostate cancer were offered participation in the 2-year extension phase , during which they would remain on their current treatment. A safety follow-up was conducted 16 weeks (+/-7 days) after withdrawal from investigational product (end of treatment or early withdrawal).	Participants were randomly assigned to receive oral bicalutamide 50 mg and dutasteride 3.5 mg once daily for 18 months. Participants who completed the 18-month treatment period with either stabilization or a positive response to their prostate cancer were offered participation in the 2-year extension phase, during which they would remain on their current treatment. A safety follow-up was conducted 16 weeks (+/-7 days) after withdrawal from investigational product (end of treatment or early withdrawal).
Measure Participants	65	62
Months 1-18, n=65, 62	37 56.9%	38 61.3%
Months 19-42, n=4, 7	0 0%	0 0%
Overall (Months 1-42), n=65, 62	37 56.9%	38 61.3%

4. Secondary Outcome

Title	Change From Baseline in Total PSA at Months 6, 12, 18, 21, and 42
Description	Change from Baseline in total PSA was measured at each scheduled post-baseline visit using a general linear model with effects for treatment and Baseline total PSA. Analysis was done using the last observation carried forward (LOCF) approach, in which missing post-Baseline values were imputed with earlier non-missing values. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame	Baseline and Months 6, 12, 18, 21, and 42

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

Arm/Group Title	Bicalutamide 50 mg/Placebo	Bicalutamide 50 mg/Dutasteride 3.5 mg
Arm/Group Description	Participants were randomly assigned to receive oral bicalutamide 50 milligrams (mg) and matching placebo once daily for 18 months. Participants who completed the 18-month treatment period with either stabilization or a positive response to their prostate cancer were offered participation in the 2-year extension phase , during which they would remain on their current treatment. A safety follow-up was conducted 16 weeks (+/-7 days) after withdrawal from investigational product (end of treatment or early withdrawal).	Participants were randomly assigned to receive oral bicalutamide 50 mg and dutasteride 3.5 mg once daily for 18 months. Participants who completed the 18-month treatment period with either stabilization or a positive response to their prostate cancer were offered participation in the 2-year extension phase, during which they would remain on their current treatment. A safety follow-up was conducted 16 weeks (+/-7 days) after withdrawal from investigational product (end of treatment or early withdrawal).
Measure Participants	65	62
Month 6, n=62, 61	-2.0	-2.2
Month 12, n=62, 61	-1.7	-2.1
Month 18, n=62, 61	-1.2	-1.7
Month 21, n=26, 30	-2.1	-1.8
Month 42, n=26, 30	-0.1	0.6

5. Secondary Outcome

Title	Number of Participants With Metastatic Disease
Description	Metastatic disease is that evidenced by a radiographic assessment. The time of metastatic disease was the date of radiographic evidence.
Time Frame	Interval of time between the date of the start of treatment and the date of radiographic evidence of metastatic disease (up to Study Month 42)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Bicalutamide 50 mg/Placebo	Bicalutamide 50 mg/Dutasteride 3.5 mg
Arm/Group Description	Participants were randomly assigned to receive oral bicalutamide 50 milligrams (mg) and matching placebo once daily for 18 months. Participants who completed the 18-month treatment period with either stabilization or a positive response to their prostate cancer were offered participation in the 2-year extension phase , during which they would remain on their current treatment. A safety follow-up was conducted 16 weeks (+/-7 days) after withdrawal from investigational product (end of treatment or early withdrawal).	Participants were randomly assigned to receive oral bicalutamide 50 mg and dutasteride 3.5 mg once daily for 18 months. Participants who completed the 18-month treatment period with either stabilization or a positive response to their prostate cancer were offered participation in the 2-year extension phase, during which they would remain on their current treatment. A safety follow-up was conducted 16 weeks (+/-7 days) after withdrawal from investigational product (end of treatment or early withdrawal).
Measure Participants	65	62
Months 1-18, n=65, 62	8 12.3%	5 8.1%
Months 19-42, n=26, 30	1 1.5%	1 1.6%
Overall (Months 1-42), n=65, 62	9 13.8%	6 9.7%

Adverse Events

Time Frame	Serious adverse events (SAEs)/non-serious AEs were collected from the first dose of investigational product to the follow-up (FU) period (16 weeks after end of study treatment) (up to approximately Study Month 46 [42 months of treatment+16 weeks of FU]).
Adverse Event Reporting Description	SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to study treatment.
Arm/Group Title	Bicalutamide 50 mg/Placebo		Bicalutamide 50 mg/Dutasteride 3.5 mg
Arm/Group Description	Participants were randomly assigned to receive oral bicalutamide 50 milligrams (mg) and matching placebo once daily for 18 months. Participants who completed the 18-month treatment period with either stabilization or a positive response to their prostate cancer were offered participation in the 2-year extension phase , during which they would remain on their current treatment. A safety follow-up was conducted 16 weeks (+/-7 days) after withdrawal from investigational product (end of treatment or early withdrawal).		Participants were randomly assigned to receive oral bicalutamide 50 mg and dutasteride 3.5 mg once daily for 18 months. Participants who completed the 18-month treatment period with either stabilization or a positive response to their prostate cancer were offered participation in the 2-year extension phase, during which they would remain on their current treatment. A safety follow-up was conducted 16 weeks (+/-7 days) after withdrawal from investigational product (end of treatment or early withdrawal).
All Cause Mortality
	Bicalutamide 50 mg/Placebo		Bicalutamide 50 mg/Dutasteride 3.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Bicalutamide 50 mg/Placebo		Bicalutamide 50 mg/Dutasteride 3.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/65 (47.7%)		30/62 (48.4%)
Blood and lymphatic system disorders
Anaemia	2/65 (3.1%)		1/62 (1.6%)
Cardiac disorders
Myocardial infarction	2/65 (3.1%)		2/62 (3.2%)
Cardiac failure congestive	1/65 (1.5%)		2/62 (3.2%)
Acute myocardial infarction	0/65 (0%)		1/62 (1.6%)
Angina pectoris	1/65 (1.5%)		0/62 (0%)
Atrial fibrillation	0/65 (0%)		1/62 (1.6%)
Cardiac arrest	0/65 (0%)		1/62 (1.6%)
Cardio-respiratory arrest	1/65 (1.5%)		0/62 (0%)
Coronary artery disease	0/65 (0%)		1/62 (1.6%)
Supraventricular tachycardia	1/65 (1.5%)		0/62 (0%)
Ear and labyrinth disorders
Vertigo	0/65 (0%)		1/62 (1.6%)
Gastrointestinal disorders
Lower gastrointestinal haemorrhage	2/65 (3.1%)		0/62 (0%)
Faecaloma	1/65 (1.5%)		1/62 (1.6%)
Colitis	1/65 (1.5%)		0/62 (0%)
Gastrointestinal haemorrhage	1/65 (1.5%)		0/62 (0%)
Hiatus hernia	1/65 (1.5%)		0/62 (0%)
General disorders
Non-cardiac chest pain	2/65 (3.1%)		0/62 (0%)
Chest pain	0/65 (0%)		1/62 (1.6%)
Oedema peripheral	0/65 (0%)		1/62 (1.6%)
Hepatobiliary disorders
Cholecystitis acute	1/65 (1.5%)		0/62 (0%)
Infections and infestations
Pneumonia	3/65 (4.6%)		0/62 (0%)
Cellulitis	0/65 (0%)		2/62 (3.2%)
Lobar pneumonia	1/65 (1.5%)		1/62 (1.6%)
Urinary tract infection	1/65 (1.5%)		1/62 (1.6%)
Orchitis	1/65 (1.5%)		0/62 (0%)
Urosepsis	1/65 (1.5%)		0/62 (0%)
Streptococcal bacteraemia	1/65 (1.5%)		0/62 (0%)
Sepsis syndrome	1/65 (1.5%)		0/62 (0%)
Injury, poisoning and procedural complications
Hip fracture	0/65 (0%)		2/62 (3.2%)
Rib fracture	1/65 (1.5%)		1/62 (1.6%)
Femoral neck fracture	1/65 (1.5%)		0/62 (0%)
Heat stroke	1/65 (1.5%)		0/62 (0%)
Humerus fracture	0/65 (0%)		1/62 (1.6%)
Subdural haematoma	1/65 (1.5%)		0/62 (0%)
Postoperative ileus	1/65 (1.5%)		0/62 (0%)
Investigations
Blood pressure increased	0/65 (0%)		1/62 (1.6%)
Metabolism and nutrition disorders
Dehydration	0/65 (0%)		1/62 (1.6%)
Diabetes mellitus inadequate control	0/65 (0%)		1/62 (1.6%)
Failure to thrive	0/65 (0%)		1/62 (1.6%)
Hypoglycaemia	0/65 (0%)		1/62 (1.6%)
Decreased appetite	1/65 (1.5%)		0/62 (0%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	1/65 (1.5%)		0/62 (0%)
Pain in extremity	1/65 (1.5%)		0/62 (0%)
Rhabdomyolysis	0/65 (0%)		1/62 (1.6%)
Spinal column stenosis	0/65 (0%)		1/62 (1.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	0/65 (0%)		2/62 (3.2%)
Rectal cancer	0/65 (0%)		1/62 (1.6%)
Refractory anaemia with an excess of blasts	0/65 (0%)		1/62 (1.6%)
Lung neoplasm malignant	0/65 (0%)		1/62 (1.6%)
Malignant lymphoid neoplasm	0/65 (0%)		1/62 (1.6%)
Nervous system disorders
Cerebrovascular accident	2/65 (3.1%)		2/62 (3.2%)
Transient ischaemic attack	0/65 (0%)		2/62 (3.2%)
Dizziness	1/65 (1.5%)		0/62 (0%)
Headache	1/65 (1.5%)		0/62 (0%)
Loss of consciousness	1/65 (1.5%)		0/62 (0%)
Presyncope	1/65 (1.5%)		0/62 (0%)
Syncope	1/65 (1.5%)		0/62 (0%)
Parkinson's disease	1/65 (1.5%)		0/62 (0%)
Psychiatric disorders
Mental status changes	2/65 (3.1%)		1/62 (1.6%)
Completed suicide	0/65 (0%)		1/62 (1.6%)
Confusional state	1/65 (1.5%)		0/62 (0%)
Renal and urinary disorders
Renal failure	2/65 (3.1%)		0/62 (0%)
Urinary retention	2/65 (3.1%)		0/62 (0%)
Haematuria	0/65 (0%)		1/62 (1.6%)
Renal failure acute	0/65 (0%)		1/62 (1.6%)
Renal failure chronic	1/65 (1.5%)		0/62 (0%)
Postrenal failure	1/65 (1.5%)		0/62 (0%)
Urethral stenosis	1/65 (1.5%)		0/62 (0%)
Bladder outlet obstruction	1/65 (1.5%)		0/62 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/65 (0%)		1/62 (1.6%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	2/65 (3.1%)		1/62 (1.6%)
Chronic obstructive pulmonary disease	2/65 (3.1%)		1/62 (1.6%)
Atelectasis	1/65 (1.5%)		1/62 (1.6%)
Hypoxia	1/65 (1.5%)		1/62 (1.6%)
Pleural effusion	1/65 (1.5%)		1/62 (1.6%)
Asthma	1/65 (1.5%)		0/62 (0%)
Pneumonia aspiration	1/65 (1.5%)		0/62 (0%)
Respiratory failure	0/65 (0%)		1/62 (1.6%)
Vascular disorders
Aortic aneurysm	0/65 (0%)		1/62 (1.6%)
Lymphoedema	0/65 (0%)		1/62 (1.6%)
Peripheral vascular disorder	0/65 (0%)		1/62 (1.6%)
Deep vein thrombosis	0/65 (0%)		1/62 (1.6%)
Peripheral artery aneurysm	0/65 (0%)		1/62 (1.6%)
Other (Not Including Serious) Adverse Events
	Bicalutamide 50 mg/Placebo		Bicalutamide 50 mg/Dutasteride 3.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	48/65 (73.8%)		51/62 (82.3%)
Blood and lymphatic system disorders
Anaemia	7/65 (10.8%)		6/62 (9.7%)
Gastrointestinal disorders
Constipation	8/65 (12.3%)		6/62 (9.7%)
Diarrhoea	8/65 (12.3%)		5/62 (8.1%)
Nausea	4/65 (6.2%)		4/62 (6.5%)
Vomiting	4/65 (6.2%)		2/62 (3.2%)
General disorders
Oedema peripheral	8/65 (12.3%)		9/62 (14.5%)
Fatigue	7/65 (10.8%)		5/62 (8.1%)
Asthenia	6/65 (9.2%)		5/62 (8.1%)
Infections and infestations
Urinary tract infection	8/65 (12.3%)		10/62 (16.1%)
Nasopharyngitis	7/65 (10.8%)		6/62 (9.7%)
Upper respiratory tract infection	6/65 (9.2%)		3/62 (4.8%)
Sinusitis	4/65 (6.2%)		3/62 (4.8%)
Ear infection	4/65 (6.2%)		1/62 (1.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	6/65 (9.2%)		5/62 (8.1%)
Back pain	2/65 (3.1%)		8/62 (12.9%)
Pain in extremity	1/65 (1.5%)		5/62 (8.1%)
Nervous system disorders
Dizziness	9/65 (13.8%)		7/62 (11.3%)
Headache	6/65 (9.2%)		2/62 (3.2%)
Renal and urinary disorders
Urinary retention	5/65 (7.7%)		2/62 (3.2%)
Haematuria	6/65 (9.2%)		0/62 (0%)
Pollakiuria	2/65 (3.1%)		4/62 (6.5%)
Urinary incontinence	4/65 (6.2%)		2/62 (3.2%)
Nocturia	5/65 (7.7%)		0/62 (0%)
Reproductive system and breast disorders
Breast tenderness	4/65 (6.2%)		2/62 (3.2%)
Nipple pain	1/65 (1.5%)		4/62 (6.5%)
Respiratory, thoracic and mediastinal disorders
Cough	3/65 (4.6%)		4/62 (6.5%)
Vascular disorders
Hot flush	9/65 (13.8%)		3/62 (4.8%)
Hypertension	6/65 (9.2%)		2/62 (3.2%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.