Study of Tadalafil Once-a Day for 12 Weeks in Men With Signs and Symptoms of Benign Prostatic Hyperplasia

• ClinicalTrials.gov Identifier: NCT00384930
• Recruitment Status: Completed
• First Posted: October 6, 2006
• Results First Posted: August 19, 2009
• Last Update Posted: September 2, 2009
• Sponsor: Eli Lilly and Company
• Collaborator: ICOS Corporation
• Information provided by: Eli Lilly and Company

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Benign Prostatic Hyperplasia
• Interventions: Drug: tadalafil; Drug: placebo
• Enrollment: 1058

Participant Flow

Recruitment Details
Pre-assignment Details	Prior to randomization, participants had a 1-4 week Screening/Wash-out Period, followed by a 4 week Placebo Run-In Period. 1813 participants were screened with 755 screen failures, and 1058 participants randomized. The two participants who did not receive study drug were not included in the baseline demographics table.

Arm/Group Title	Placebo	2.5 mg Tadalafil	5 mg Tadalafil	10 mg Tadalafil	20 mg Tadalafil
Arm/Group Description	placebo tablet by mouth once a day for twelve weeks	2.5 mg tadalafil tablet by mouth once a day for twelve weeks	5 mg tadalafil tablet by mouth once a day for twelve weeks	10 mg tadalafil tablet by mouth once a day for twelve weeks	20 mg tadalafil tablet by mouth once a day for twelve weeks
Period Title: Overall Study
Started	212	209	212	216	209
Received Double-Blind Study Drug	211	208	212	216	209
Completed	185	182	182	175	162
Not Completed	27	27	30	41	47
Reason Not Completed
Adverse Event	5	4	12	11	14
Entry Criteria Not Met	2	6	7	8	4
Lack of Efficacy	1	1	2	1	2
Lost to Follow-up	5	3	0	4	6
Physician Decision	0	1	1	0	1
Protocol Violation	1	0	1	6	4
Sponsor Decision	3	4	0	5	0
Withdrawal by Subject	9	7	7	6	16
Didn't Receive Double-Blind Study Drug	1	1	0	0	0

Baseline Characteristics

Arm/Group Title		Placebo	2.5 mg Tadalafil	5 mg Tadalafil	10 mg Tadalafil	20 mg Tadalafil	Total
Arm/Group Description		placebo tablet by mouth once a day for twelve weeks	2.5 mg tadalafil tablet by mouth once a day for twelve weeks	5 mg tadalafil tablet by mouth once a day for twelve weeks	10 mg tadalafil tablet by mouth once a day for twelve weeks	20 mg tadalafil tablet by mouth once a day for twelve weeks	Total of all reporting groups
Overall Number of Baseline Participants		211	208	212	216	209	1056
Baseline Analysis Population Description		[Not Specified]
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	211 participants	208 participants	212 participants	216 participants	209 participants	1056 participants
		61.75 (7.69)	62.03 (8.42)	61.95 (8.17)	62.22 (7.20)	62.55 (8.09)	62.10 (7.91)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	211 participants	208 participants	212 participants	216 participants	209 participants	1056 participants
	Female	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Male	211 100.0%	208 100.0%	212 100.0%	216 100.0%	209 100.0%	1056 100.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	211 participants	208 participants	212 participants	216 participants	209 participants	1056 participants
Australia		4	5	5	6	4	24
Canada		12	5	9	13	6	45
France		13	12	9	15	11	60
Germany		29	35	39	28	33	164
Greece		8	9	12	11	10	50
Italy		15	10	5	9	9	48
Mexico		19	16	17	19	19	90
Spain		3	3	2	5	4	17
Sweden		4	2	5	4	5	20
United States		105	112	109	106	108	540
Baseline (Visit 3) Lower Urinary Tract Symptoms (LUTS) Severity [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	211 participants	208 participants	212 participants	216 participants	209 participants	1056 participants
Moderate (<20 units on a scale: IPSS)		137	139	141	143	141	701
Severe (>=20 units on a scale: IPSS)		74	69	71	72	68	354
Unknown		0	0	0	1	0	1
		[1] Measure Description: LUTS Severity was measured with the International Prostate Symptom Score (IPSS), which has a scoring range of 0 to 35. Total scores: 0-7 Mildly symptomatic; 8-19 moderately symptomatic; 20-35 severely symptomatic.
Duration of Lower Urinary Tract Symptoms (LUTS) Secondary to Benign Prostatic Hyperplasia (BPH); Measure Type: Number; Unit of measure: Participants	Number Analyzed	211 participants	208 participants	212 participants	216 participants	209 participants	1056 participants
< 6 months		0	0	0	1	0	1
6 months to 1 year		44	27	37	27	39	174
1 year to 3 years		62	64	63	81	70	340
> 3 years		105	117	112	107	100	541
Erectile Dysfunction; Measure Type: Number; Unit of measure: Participants	Number Analyzed	211 participants	208 participants	212 participants	216 participants	209 participants	1056 participants
Yes		142	135	144	150	145	716
No		67	71	68	64	61	331
Unknown		1	2	0	2	3	8
Not Collected		1	0	0	0	0	1
Previous Therapy for Benign Prostatic Hyperplasia (BPH); Measure Type: Number; Unit of measure: Participants	Number Analyzed	211 participants	208 participants	212 participants	216 participants	209 participants	1056 participants
No		153	139	158	160	152	762
Yes		58	69	54	56	57	294
Race/Ethnicity; Measure Type: Number; Unit of measure: Participants	Number Analyzed	211 participants	208 participants	212 participants	216 participants	209 participants	1056 participants
African		3	3	7	5	5	23
Caucasian		179	184	179	186	176	904
East Asian		0	1	1	0	0	2
Hispanic		29	20	25	24	25	123
West Asian		0	0	0	1	3	4
Severity of Erectile Dysfunction (ED) [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	211 participants	208 participants	212 participants	216 participants	209 participants	1056 participants
Mild		38	42	41	56	40	217
Moderate		82	75	82	72	79	390
Severe		22	18	21	22	26	109
		[1] Measure Description: Severity was determine only on participants with Erectile Dysfunction using scores on International Index of Erectile Function (IIEF) EF Domain (sum of the scores for Questions 1 through 5 and Question 15) with a range of 0 to 30. Normal EF (≥26), mild ED (17 to 25), moderate ED (11 to 16), and severe ED (1 to 10).
Sexually Active; Measure Type: Number; Unit of measure: Participants	Number Analyzed	211 participants	208 participants	212 participants	216 participants	209 participants	1056 participants
No		42	40	33	42	48	205
Yes		169	168	179	174	161	851
Sexually Active and Erectile Dysfunction (ED); Measure Type: Number; Unit of measure: Participants	Number Analyzed	211 participants	208 participants	212 participants	216 participants	209 participants	1056 participants
Sexually Active with ED		115	113	117	120	116	581
Sexually Active without ED		54	55	62	54	45	270
Not Sexually Active with ED		26	21	25	28	28	128
Not Sexually Active without ED		15	17	8	12	18	70
Sexual Activity and/or ED Status is Unknown		1	2	0	2	2	7

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS): Primary Analysis
Description	Assesses the severity of BPH-LUTS and the response to therapy. The total score was derived by summing the scores of the responses to the 7 component questions. Scores range from 0 to 35; 0-7 Mildly symptomatic; 8-19 moderately symptomatic; 20-35 severely symptomatic.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Primary analysis was performed on an intent-to-treat basis. Data from subjects with baseline and at least one postbaseline were used for the analysis. Last observation carried forward.

Arm/Group Title	Placebo	5 mg Tadalafil
Arm/Group Description:	placebo tablet taken by mouth once a day for 12 weeks	5 mg tadalafil tablet taken by mouth once a day for 12 weeks
Overall Number of Participants Analyzed	205	205
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	17.08 (6.36)	17.30 (5.97)
Change from Baseline	-2.25 (6.17)	-4.92 (5.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 5 mg Tadalafil
	Comments	This is the principal inferential analysis of the primary outcome.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	P-value for Change from Baseline. Change = Endpoint minus Baseline.
	Method	Permutation Test
	Comments	[Not Specified]

2. Primary Outcome

Title	Change From Baseline to Week 12 in International Prostate Symptom Score (IPSS): Supportive Analysis
Description	Assesses the severity of BPH-LUTS and the response to therapy. The total score was derived by summing the scores of the responses to the 7 component questions. Scores range from 0 to 35; 0-7 Mildly symptomatic; 8-19 moderately symptomatic; 20-35 severely symptomatic.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Primary analysis was performed on an intent-to-treat basis. Data from subjects with baseline and at least one postbaseline were used for the analysis. Last observation carried forward.

Arm/Group Title	Placebo	2.5 mg Tadalafil	5 mg Tadalafil	10 mg Tadalafil	20 mg Tadalafil
Arm/Group Description:	placebo tablet by mouth once a day for twelve weeks	2.5 mg tadalafil tablet by mouth once a day for twelve weeks	5 mg tadalafil tablet by mouth once a day for twelve weeks	10 mg tadalafil tablet by mouth once a day for twelve weeks	20 mg tadalafil tablet by mouth once a day for twelve weeks
Overall Number of Participants Analyzed	205	201	205	207	199
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
	-2.23 (0.49)	-3.81 (0.50)	-4.83 (0.49)	-5.13 (0.48)	-5.17 (0.50)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2.5 mg Tadalafil
	Comments	This is a supportive analysis of the primary outcome.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.005
	Comments	P-values are from an ANCOVA model with effect of treatment group, geographic region, and IPSS baseline value (at Visit 3) as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.58
	Confidence Interval	95%; -2.68 to -0.48
	Estimation Comments	Mean Difference = 2.5 mg Tadalafil minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 5 mg Tadalafil
	Comments	This is a supportive analysis of the primary outcome.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	P-values are from an ANCOVA model with effect of treatment group, geographic region, and IPSS baseline value (at Visit 3) as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.60
	Confidence Interval	95%; -3.69 to -1.51
	Estimation Comments	Mean Difference = 5 mg Tadalafil minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg Tadalafil
	Comments	This is a supportive analysis of the primary outcome.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	P-values are from an ANCOVA model with effect of treatment group, geographic region, and IPSS baseline value (at Visit 3) as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.90
	Confidence Interval	95%; -3.99 to -1.81
	Estimation Comments	Mean Difference = 10 mg Tadalafil minus Placebo

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 20 mg Tadalafil
	Comments	This is a supportive analysis of the primary outcome.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	P-values are from an ANCOVA model with effect of treatment group, geographic region, and IPSS baseline value (at Visit 3) as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.94
	Confidence Interval	95%; -4.04 to -1.84
	Estimation Comments	Mean Difference = 20 mg Tadalafil minus Placebo

3. Secondary Outcome

Title	Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) (Irritative) Subscore
Description	Measures irritative symptoms over the past 4 weeks of the IPSS. IPSS irritative subscore is the sum of Questions 2, 4 and 7 of the IPSS questionnaire. Scores range from 1 (few irritative symptoms) to 5 (frequent irritative symptoms), thus the 3 questions of the irritative subscore range from 0 to 15.
Time Frame	baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Secondary continuous analyses were performed on an intent-to-treat basis. Data from subjects with baseline and at least one postbaseline were used for the analysis. Last observation carried forward.

Arm/Group Title	Placebo	2.5 mg Tadalafil	5 mg Tadalafil	10 mg Tadalafil	20 mg Tadalafil
Arm/Group Description:	placebo tablet by mouth once a day for twelve weeks	2.5 mg tadalafil tablet by mouth once a day for twelve weeks	5 mg tadalafil tablet by mouth once a day for twelve weeks	10 mg tadalafil tablet by mouth once a day for twelve weeks	20 mg tadalafil tablet by mouth once a day for twelve weeks
Overall Number of Participants Analyzed	205	201	205	208	199
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	7.58 (3.09)	7.78 (2.86)	7.65 (2.84)	7.88 (2.67)	7.53 (3.07)
Change from Baseline	-0.99 (2.92)	-1.62 (2.83)	-1.91 (2.64)	-2.04 (2.75)	-2.05 (2.86)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2.5 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.025
	Comments	P-value for Change from Baseline. Change=Endpoint - Baseline. P-values from ANCOVA model with effect of treatment group, geographic region, and baseline value of analyzed variable as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.57
	Confidence Interval	95%; -1.08 to -0.07
	Estimation Comments	Mean Difference = 2.5 mg Tadalafil minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 5 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	P-value for Change from Baseline. Change=Endpoint - Baseline. P-values from ANCOVA model with effect of treatment group, geographic region, and baseline value of analyzed variable as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.90
	Confidence Interval	95%; -1.40 to -0.40
	Estimation Comments	Mean Difference = 5 mg Tadalafil minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	P-value for Change from Baseline. Change=Endpoint - Baseline. P-values from ANCOVA model with effect of treatment group, geographic region, and baseline value of analyzed variable as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.96
	Confidence Interval	95%; -1.45 to -0.46
	Estimation Comments	Mean Difference = 10 mg Tadalafil minus Placebo

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 20 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	P-value for Change from Baseline. Change=Endpoint - Baseline. P-values from ANCOVA model with effect of treatment group, geographic region, and baseline value of analyzed variable as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.07
	Confidence Interval	95%; -1.58 to -0.57
	Estimation Comments	Mean Difference = 20 mg Tadalafil minus Placebo

4. Secondary Outcome

Title	Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore
Description	Measures obstructive symptoms over the past 4 weeks of the IPSS. IPSS obstructive subscore is the sum of Questions 1, 3, 5 and 6 of the IPSS questionnaire. Scores range from 1 (few obstructive symptoms) to 5 (frequent obstructive symptoms), thus the 4 questions of the obstructive score range from 0 to 20.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Secondary continuous analyses were performed on an intent-to-treat basis. Data from subjects with baseline and at least one postbaseline were used for the analysis. Last observation carried forward.

Arm/Group Title	Placebo	2.5 mg Tadalafil	5 mg Tadalafil	10 mg Tadalafil	20 mg Tadalafil
Arm/Group Description:	placebo tablet by mouth once a day for twelve weeks	2.5 mg tadalafil tablet by mouth once a day for twelve weeks	5 mg tadalafil tablet by mouth once a day for twelve weeks	10 mg tadalafil tablet by mouth once a day for twelve weeks	20 mg tadalafil tablet by mouth once a day for twelve weeks
Overall Number of Participants Analyzed	205	202	205	207	199
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	9.51 (4.21)	9.71 (4.16)	9.65 (4.10)	9.88 (3.87)	9.57 (4.45)
Change from Baseline	-1.27 (4.00)	-2.31 (3.84)	-3.00 (3.87)	-3.29 (4.04)	-3.17 (4.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2.5 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.008
	Comments	P-value for Change from Baseline. Change=Endpoint - Baseline. P-values from ANCOVA model with effect of treatment group, geographic region, and baseline value of analyzed variable as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.97
	Confidence Interval	95%; -1.69 to -0.26
	Estimation Comments	Mean Difference = 2.5 mg Tadalafil minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 5 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	P-value for Change from Baseline. Change=Endpoint - Baseline. P-values from ANCOVA model with effect of treatment group, geographic region, and baseline value of analyzed variable as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.69
	Confidence Interval	95%; -2.40 to -0.98
	Estimation Comments	Mean Difference = 5 mg Tadalafil minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	P-value for Change from Baseline. Change=Endpoint - Baseline. P-values from ANCOVA model with effect of treatment group, geographic region, and baseline value of analyzed variable as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.89
	Confidence Interval	95%; -2.60 to -1.18
	Estimation Comments	Mean Difference = 10 mg Tadalafil minus Placebo

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 20 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	P-value for Change from Baseline. Change=Endpoint - Baseline. P-values from ANCOVA model with effect of treatment group, geographic region, and baseline value of analyzed variable as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.87
	Confidence Interval	95%; -2.59 to -1.15
	Estimation Comments	Mean Difference = 20 mg Tadalafil minus Placebo

5. Secondary Outcome

Title	Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Question 7 (Nocturia)
Description	Measures nocturia (the need to get up at night to urinate) over the past 4 weeks. Scores range from 1 (few episodes of nocturia) to 5 (frequent episodes of nocturia).
Time Frame	baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Secondary continuous analyses were performed on an intent-to-treat basis. Data from subjects with baseline and at least one postbaseline were used for the analysis. Last observation carried forward.

Arm/Group Title	Placebo	2.5 mg Tadalafil	5 mg Tadalafil	10 mg Tadalafil	20 mg Tadalafil
Arm/Group Description:	placebo tablet by mouth once a day for twelve weeks	2.5 mg tadalafil tablet by mouth once a day for twelve weeks	5 mg tadalafil tablet by mouth once a day for twelve weeks	10 mg tadalafil tablet by mouth once a day for twelve weeks	20 mg tadalafil tablet by mouth once a day for twelve weeks
Overall Number of Participants Analyzed	205	201	205	208	199
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	2.36 (1.10)	2.37 (1.31)	2.36 (1.91)	2.36 (1.15)	2.20 (1.23)
Change from Baseline	-0.36 (1.09)	-0.43 (1.33)	-0.49 (1.17)	-0.43 (1.28)	-0.54 (1.17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2.5 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.503
	Comments	P-value for Change from Baseline. Change=Endpoint - Baseline. P-values from ANCOVA model with effect of treatment group, geographic region, and baseline value of analyzed variable as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.07
	Confidence Interval	95%; -0.28 to 0.14
	Estimation Comments	Mean Difference = 2.5 mg Tadalafil minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 5 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.206
	Comments	P-value for Change from Baseline. Change=Endpoint - Baseline. P-values from ANCOVA model with effect of treatment group, geographic region, and baseline value of analyzed variable as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.13
	Confidence Interval	95%; -0.34 to 0.07
	Estimation Comments	Mean Difference = 5 mg Tadalafil minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.452
	Comments	P-value for Change from Baseline. Change=Endpoint - Baseline. P-values from ANCOVA model with effect of treatment group, geographic region, and baseline value of analyzed variable as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.08
	Confidence Interval	95%; -0.28 to 0.13
	Estimation Comments	Mean Difference = 10 mg Tadalafil minus Placebo

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 20 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.012
	Comments	P-value for Change from Baseline. Change=Endpoint - Baseline. P-values from ANCOVA model with effect of treatment group, geographic region, and baseline value of analyzed variable as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.26
	Confidence Interval	95%; -0.47 to -0.06
	Estimation Comments	Mean Difference = 20 mg Tadalafil minus Placebo

6. Secondary Outcome

Title	Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index
Description	Assessment of quality of life (QOL) by urinary symptoms, with scores ranging from 0 (delighted) to 6 (terrible).
Time Frame	baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Secondary continuous analyses were performed on an intent-to-treat basis. Data from subjects with baseline and at least one postbaseline were used for the analysis. Last observation carried forward.

Arm/Group Title	Placebo	2.5 mg Tadalafil	5.0 mg Tadalafil	10 mg Tadalafil	20 mg Tadalafil
Arm/Group Description:	placebo tablet by mouth once a day for twelve weeks	2.5 mg tadalafil tablet by mouth once a day for twelve weeks	5.0 mg tadalafil tablet by mouth once a day for twelve weeks	10 mg tadalafil tablet by mouth once a day for twelve weeks	20 mg tadalafil tablet by mouth once a day for twelve weeks
Overall Number of Participants Analyzed	205	202	205	206	199
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	3.57 (1.19)	3.69 (1.19)	3.54 (1.30)	3.55 (1.23)	3.59 (1.28)
Change from Baseline	-0.56 (1.20)	-0.86 (1.13)	-0.92 (1.30)	-0.98 (1.46)	-0.97 (1.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2.5 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.029
	Comments	P-value for Change from Baseline. Change=Endpoint - Baseline. P-values from ANCOVA model with effect of treatment group, geographic region, and baseline value of analyzed variable as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.26
	Confidence Interval	95%; -0.49 to -0.03
	Estimation Comments	Mean Difference = 2.5 mg Tadalafil minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 5.0 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.002
	Comments	P-value for Change from Baseline. Change=Endpoint - Baseline. P-values from ANCOVA model with effect of treatment group, geographic region, and baseline value of analyzed variable as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.37
	Confidence Interval	95%; -0.60 to -0.14
	Estimation Comments	Mean Difference = 5 mg Tadalafil minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	P-value for Change from Baseline. Change=Endpoint - Baseline. P-values from ANCOVA model with effect of treatment group, geographic region, and baseline value of analyzed variable as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.43
	Confidence Interval	95%; -0.66 to -0.19
	Estimation Comments	Mean Difference = 10 mg Tadalafil minus Placebo

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 20 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	P-value for Change from Baseline. Change=Endpoint - Baseline. P-values from ANCOVA model with effect of treatment group, geographic region, and baseline value of analyzed variable as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.40
	Confidence Interval	95%; -0.64 to -0.17
	Estimation Comments	Mean Difference = 20 mg Tadalafil minus Placebo

7. Secondary Outcome

Title	Change From Baseline to 12 Week Endpoint in Benign Prostatic Hyperplasia Impact Index (BII)
Description	Measures the impact that symptoms of BPH has on the patients well being. This questionnaire has 4 questions assessing the level of urinary discomfort and it's impact on the patients. Three questions range from 0 (no impact) to 4 (high impact); one question ranges from 0 (low impact) to 4 (high impact). The BII score ranges from 0 to 16.
Time Frame	baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Secondary continuous analyses were performed on an intent-to-treat basis. Data from subjects with baseline and at least one postbaseline were used for the analysis. Last observation carried forward.

Arm/Group Title	Placebo	2.5 mg Tadalafil	5 mg Tadalafil	10 mg Tadalafil	20 mg Tadalafil
Arm/Group Description:	placebo tablet by mouth once a day for twelve weeks	2.5 mg tadalafil tablet by mouth once a day for twelve weeks	5 mg tadalafil tablet by mouth once a day for twelve weeks	10 mg tadalafil tablet by mouth once a day for twelve weeks	20 mg tadalafil tablet by mouth once a day for twelve weeks
Overall Number of Participants Analyzed	205	201	204	209	199
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	4.94 (2.95)	4.73 (2.95)	4.66 (2.98)	4.86 (2.98)	4.75 (2.79)
Change from Baseline	-0.79 (2.52)	-0.83 (2.66)	-1.25 (2.75)	-1.31 (2.79)	-1.34 (2.41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2.5 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.583
	Comments	P-value for Change from Baseline. Change=Endpoint - Baseline. P-values from ANCOVA model with effect of treatment group, geographic region, and baseline value of analyzed variable as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.13
	Confidence Interval	95%; -0.58 to 0.33
	Estimation Comments	Mean Difference = 2.5 mg Tadalafil minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 5 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.013
	Comments	P-value for Change from Baseline. Change=Endpoint - Baseline. P-values from ANCOVA model with effect of treatment group, geographic region, and baseline value of analyzed variable as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.57
	Confidence Interval	95%; -1.03 to -0.12
	Estimation Comments	Mean Difference = 5 mg Tadalafil minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.016
	Comments	P-value for Change from Baseline. Change=Endpoint - Baseline. P-values from ANCOVA model with effect of treatment group, geographic region, and baseline value of analyzed variable as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.55
	Confidence Interval	95%; -1.00 to -0.10
	Estimation Comments	Mean Difference = 10 mg Tadalafil minus Placebo

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 20 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.007
	Comments	P-value for Change from Baseline. Change=Endpoint - Baseline. P-values from ANCOVA model with effect of treatment group, geographic region, and baseline value of analyzed variable as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.62
	Confidence Interval	95%; -1.08 to -0.17
	Estimation Comments	Mean Difference = 20 mg Tadalafil minus Placebo

8. Secondary Outcome

Title	Number of Participants Who Answer "Yes" to the Lower Urinary Tract Symptoms (LUTS) Global Assessment Question (LUTS-GAQ)
Description	LUTS-GAQ Question asks the participant if the treatment they have been on has improved their uninary symptoms.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Secondary continuous analyses were performed on an intent-to-treat basis. Data from subjects with baseline and at least one postbaseline were used for the analysis. Last observation carried forward.

Arm/Group Title	Placebo	2.5 mg Tadalafil	5 mg Tadalafil	10 mg Tadalafil	20 mg Tadalafil
Arm/Group Description:	placebo tablet by mouth once a day for twelve weeks	2.5 mg tadalafil tablet by mouth once a day for twelve weeks	5 mg tadalafil tablet by mouth once a day for twelve weeks	10 mg tadalafil tablet by mouth once a day for twelve weeks	20 mg tadalafil tablet by mouth once a day for twelve weeks
Overall Number of Participants Analyzed	199	194	201	200	186
Measure Type: Number; Unit of Measure: participants
	109	120	139	146	138

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2.5 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.133
	Comments	P-values are from Cochran-Mantel-Haenszel test stratified by the randomization strata factors (4 geographic regions, 2 levels of IPSS severity, 2 levels of ED history) as fixed effect, and were not adjusted for multiple comparisons.
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 5 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.003
	Comments	P-values are from Cochran-Mantel-Haenszel test stratified by the randomization strata factors (4 geographic regions, 2 levels of IPSS severity, 2 levels of ED history) as fixed effect, and were not adjusted for multiple comparisons.
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	P-values are from Cochran-Mantel-Haenszel test stratified by the randomization strata factors (4 geographic regions, 2 levels of IPSS severity, 2 levels of ED history) as fixed effect, and were not adjusted for multiple comparisons.
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 20 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	P-values are from Cochran-Mantel-Haenszel test stratified by the randomization strata factors (4 geographic regions, 2 levels of IPSS severity, 2 levels of ED history) as fixed effect, and were not adjusted for multiple comparisons.
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

9. Secondary Outcome

Title	Change From Baseline to 12 Week Endpoint in Peak Urinary Flow
Description	Measures the maximum flow rate of urine (measured in mL/s). This is a continuous parameter with positive numeric values.
Time Frame	baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Secondary continuous analyses were performed on an intent-to-treat basis. Data from subjects with baseline and at least one postbaseline were used for the analysis. Last observation carried forward.

Arm/Group Title	Placebo	2.5 mg Tadalafil	5 mg Tadalafil	10 mg Tadalafil	20 mg Tadalafil
Arm/Group Description:	placebo tablet by mouth once a day for twelve weeks	2.5 mg tadalafil tablet by mouth once a day for twelve weeks	5 mg tadalafil tablet by mouth once a day for twelve weeks	10 mg tadalafil tablet by mouth once a day for twelve weeks	20 mg tadalafil tablet by mouth once a day for twelve weeks
Overall Number of Participants Analyzed	198	201	202	201	190
Mean (Standard Deviation); Unit of Measure: milliliter per second
Baseline	10.31 (4.85)	9.97 (4.09)	10.37 (3.86)	9.93 (3.77)	9.82 (3.97)
Change from Baseline	1.23 (5.01)	1.50 (4.56)	1.61 (3.95)	1.69 (4.46)	2.15 (4.69)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2.5 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.735
	Comments	P-value for Change from Baseline. Change=Endpoint - Baseline. P-values from ANCOVA model with effect of treatment group, geographic region, and baseline value of analyzed variable as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.14
	Confidence Interval	95%; -0.69 to 0.98
	Estimation Comments	Mean Difference = 2.5 mg Tadalafil minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 5 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.355
	Comments	P-value for Change from Baseline. Change=Endpoint - Baseline. P-values from ANCOVA model with effect of treatment group, geographic region, and baseline value of analyzed variable as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.39
	Confidence Interval	95%; -0.44 to 1.23
	Estimation Comments	Mean Difference = 5 mg Tadalafil minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.433
	Comments	P-value for Change from Baseline. Change=Endpoint - Baseline. P-values from ANCOVA model with effect of treatment group, geographic region, and baseline value of analyzed variable as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.34
	Confidence Interval	95%; -0.50 to 1.17
	Estimation Comments	Mean Difference = 10 mg Tadalafil minus Placebo

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 20 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.089
	Comments	P-value for Change from Baseline. Change=Endpoint - Baseline. P-values from ANCOVA model with effect of treatment group, geographic region, and baseline value of analyzed variable as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.74
	Confidence Interval	95%; -0.11 to 1.59
	Estimation Comments	Mean Difference = 20 mg Tadalafil minus Placebo

10. Secondary Outcome

Title	Change From Baseline to 12 Week Endpoint in International Index of Erectile Function (IIEF) EF Domain
Description	Measures erectile function over the past 4 weeks on Questions 1-5 and 15 (6 questions) of the International Index of Erecile Function (IIEF) questionnaire. Scores range from 0 (low/no erectile function) to 5 (high erectile function), thus the 6 questions of the IIEF-EF domain range from 0 to 30.
Time Frame	baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Secondary continuous analyses were performed on an intent-to-treat basis. Data from all randomized and sexually active subjects with a history of ED and non-missing data at baseline and at least one postbaseline visit were used for the analysis. Last observation carried forward.

Arm/Group Title	Placebo	2.5 mg Tadalafil	5 mg Tadalafil	10 mg Tadalafil	20 mg Tadalafil
Arm/Group Description:	placebo tablet by mouth once a day for twelve weeks	2.5 mg tadalafil tablet by mouth once a day for twelve weeks	5 mg tadalafil tablet by mouth once a day for twelve weeks	10 mg tadalafil tablet by mouth once a day for twelve weeks	20 mg tadalafil tablet by mouth once a day for twelve weeks
Overall Number of Participants Analyzed	113	109	113	113	109
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	17.26 (7.95)	17.42 (8.30)	15.29 (8.13)	17.22 (8.43)	16.28 (8.05)
Change from Baseline	0.78 (6.32)	3.97 (7.30)	6.56 (9.43)	6.64 (8.29)	7.44 (8.42)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2.5 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	P-value for Change from Baseline. Change=Endpoint - Baseline. P-values from ANCOVA model with effect of treatment group, geographic region, and baseline value of analyzed variable as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.36
	Confidence Interval	95%; 1.56 to 5.17
	Estimation Comments	Mean Difference = 2.5 mg Tadalafil minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 5 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	P-value for Change from Baseline. Change=Endpoint - Baseline. P-values from ANCOVA model with effect of treatment group, geographic region, and baseline value of analyzed variable as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	4.75
	Confidence Interval	95%; 2.95 to 6.54
	Estimation Comments	Mean Difference = 5 mg Tadalafil minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	P-value for Change from Baseline. Change=Endpoint - Baseline. P-values from ANCOVA model with effect of treatment group, geographic region, and baseline value of analyzed variable as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	5.83
	Confidence Interval	95%; 4.04 to 7.62
	Estimation Comments	Mean Difference = 10 mg Tadalafil minus Placebo

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 20 mg Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	P-value for Change from Baseline. Change=Endpoint - Baseline. P-values from ANCOVA model with effect of treatment group, geographic region, and baseline value of analyzed variable as a covariate, and were not adjusted for multiple comparisons.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	6.15
	Confidence Interval	95%; 4.35 to 7.95
	Estimation Comments	Mean Difference = 20 mg Tadalafil minus Placebo

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Placebo		2.5 mg Tadalafil		5 mg Tadalafil		10 mg Tadalafil		20 mg Tadalafil
Arm/Group Description	placebo tablet by mouth once a day for twelve weeks		2.5 mg tadalafil tablet by mouth once a day for twelve weeks		5 mg tadalafil tablet by mouth once a day for twelve weeks		10 mg tadalafil tablet by mouth once a day for twelve weeks		20 mg tadalafil tablet by mouth once a day for twelve weeks
All-Cause Mortality
	Placebo		2.5 mg Tadalafil		5 mg Tadalafil		10 mg Tadalafil		20 mg Tadalafil
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--		--/--		--/--
Serious Adverse Events
	Placebo		2.5 mg Tadalafil		5 mg Tadalafil		10 mg Tadalafil		20 mg Tadalafil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6		3		1		2		5
Cardiac disorders
Angina unstable † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	1	0/209 (0.00%)	0
Atrial tachycardia † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Coronary artery stenosis † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Myocardial infarction † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Gastrointestinal disorders
Pancreatitis † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
Hepatobiliary disorders
Cholecystitis † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
Injury, poisoning and procedural complications
Cartilage injury † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthritis † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	1	1/209 (0.48%)	1
Back pain † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Osteoarthritis † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Rheumatoid arthritis † 1	1/212 (0.47%)	2	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder neoplasm † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Nervous system disorders
Cerebrovascular accident † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Renal and urinary disorders
Nephrolithiasis † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Renal colic † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Renal failure acute † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Ureteric rupture † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Urinary retention † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Surgical and medical procedures
Coronary arterial stent insertion † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Indwelling catheter management † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Ureteral catheterisation † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Ureteral stent insertion † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 10.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Placebo		2.5 mg Tadalafil		5 mg Tadalafil		10 mg Tadalafil		20 mg Tadalafil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43		54		65		75		80
Cardiac disorders
Arrhythmia † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Atrioventricular block second degree † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Cardiomegaly † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
Left atrial dilatation † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Sinus arrhythmia † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Tachycardia † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	1/209 (0.48%)	1
Ear and labyrinth disorders
Ear congestion † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	1	0/209 (0.00%)	0
Ear pain † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Tinnitus † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	1	0/209 (0.00%)	0
Vertigo † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	2	0/216 (0.00%)	0	1/209 (0.48%)	1
Endocrine disorders
Hypothyroidism † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Eye disorders
Choroidal neovascularisation † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
Conjunctivitis † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Eye irritation † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	1/209 (0.48%)	1
Eye pain † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Eyelid irritation † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Glaucoma † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	1	0/209 (0.00%)	0
Ocular hyperaemia † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Ocular hypertension † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
Panophthalmitis † 1	1/212 (0.47%)	2	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Photopsia † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
Retinal tear † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	2	0/216 (0.00%)	0	0/209 (0.00%)	0
Vision blurred † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
Vitreous floaters † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
Gastrointestinal disorders
Abdominal pain † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	1/212 (0.47%)	1	1/216 (0.46%)	1	1/209 (0.48%)	1
Abdominal pain lower † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Abdominal pain upper † 1	2/212 (0.94%)	2	2/209 (0.96%)	3	2/212 (0.94%)	2	3/216 (1.39%)	3	0/209 (0.00%)	0
Bowel movement irregularity † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Constipation † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	1	0/209 (0.00%)	0
Diarrhoea † 1	3/212 (1.42%)	3	2/209 (0.96%)	2	6/212 (2.83%)	12	1/216 (0.46%)	1	5/209 (2.39%)	5
Duodenogastric reflux † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Dyspepsia † 1	0/212 (0.00%)	0	2/209 (0.96%)	3	10/212 (4.72%)	15	6/216 (2.78%)	6	10/209 (4.78%)	10
Flatulence † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	1	1/209 (0.48%)	1
Gastritis † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	1/212 (0.47%)	1	3/216 (1.39%)	3	2/209 (0.96%)	2
Gastrooesophageal reflux disease † 1	0/212 (0.00%)	0	2/209 (0.96%)	2	2/212 (0.94%)	2	6/216 (2.78%)	6	3/209 (1.44%)	3
Gingival disorder † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Haemorrhoids † 1	1/212 (0.47%)	1	1/209 (0.48%)	1	0/212 (0.00%)	0	1/216 (0.46%)	1	0/209 (0.00%)	0
Hiatus hernia † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Inguinal hernia † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
Nausea † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	3/212 (1.42%)	3	0/216 (0.00%)	0	0/209 (0.00%)	0
Oesophageal pain † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	1	0/209 (0.00%)	0
Oesophagitis † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Rectal haemorrhage † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
Reflux oesophagitis † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	1	1/209 (0.48%)	1
Stomach discomfort † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Tooth loss † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
Toothache † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Vomiting † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	3/212 (1.42%)	3	0/216 (0.00%)	0	1/209 (0.48%)	1
General disorders
Asthenia † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Chest discomfort † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Chest pain † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	3/212 (1.42%)	3	0/216 (0.00%)	0	0/209 (0.00%)	0
Fatigue † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	1/212 (0.47%)	1	1/216 (0.46%)	1	0/209 (0.00%)	0
Inflammation † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
Influenza like illness † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
Irritability † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	1	0/209 (0.00%)	0
Local swelling † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Oedema † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	1/216 (0.46%)	1	0/209 (0.00%)	0
Oedema peripheral † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	1/212 (0.47%)	1	2/216 (0.93%)	2	0/209 (0.00%)	0
Pain † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	2/212 (0.94%)	2	0/216 (0.00%)	0	1/209 (0.48%)	1
Pyrexia † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	2/212 (0.94%)	2	0/216 (0.00%)	0	1/209 (0.48%)	1
Sensation of foreign body † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	2/209 (0.96%)	2
Hepatobiliary disorders
Hepatic function abnormal † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Immune system disorders
Hypersensitivity † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	1/209 (0.48%)	1
Seasonal allergy † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	2	0/216 (0.00%)	0	1/209 (0.48%)	1
Infections and infestations
Bronchitis † 1	1/212 (0.47%)	1	3/209 (1.44%)	3	1/212 (0.47%)	1	5/216 (2.31%)	5	0/209 (0.00%)	0
Cystitis † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Diverticulitis † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Ear infection † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
Folliculitis † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Fungal infection † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	1	0/209 (0.00%)	0
Gastroenteritis † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	1/216 (0.46%)	1	0/209 (0.00%)	0
Gastroenteritis viral † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	2/216 (0.93%)	2	1/209 (0.48%)	1
Herpes simplex † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Herpes zoster † 1	1/212 (0.47%)	1	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	2/209 (0.96%)	2
Influenza † 1	1/212 (0.47%)	1	4/209 (1.91%)	4	4/212 (1.89%)	4	1/216 (0.46%)	1	2/209 (0.96%)	2
Labyrinthitis † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	1	0/209 (0.00%)	0
Lower respiratory tract infection † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Nasopharyngitis † 1	2/212 (0.94%)	2	7/209 (3.35%)	8	4/212 (1.89%)	6	2/216 (0.93%)	2	5/209 (2.39%)	5
Pharyngitis † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	2/216 (0.93%)	2	0/209 (0.00%)	0
Pneumonia viral † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
Rhinitis † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
Sinusitis † 1	1/212 (0.47%)	1	1/209 (0.48%)	1	0/212 (0.00%)	0	1/216 (0.46%)	1	1/209 (0.48%)	1
Tooth abscess † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	1	0/209 (0.00%)	0
Tracheitis † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	1	0/209 (0.00%)	0
Upper respiratory tract infection † 1	2/212 (0.94%)	2	0/209 (0.00%)	0	2/212 (0.94%)	2	0/216 (0.00%)	0	1/209 (0.48%)	1
Urinary tract infection † 1	3/212 (1.42%)	3	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Injury, poisoning and procedural complications
Animal bite † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Back injury † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	1	1/209 (0.48%)	1
Excoriation † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	1	0/209 (0.00%)	0
Fall † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	1	0/209 (0.00%)	0
Foot fracture † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Joint sprain † 1	0/212 (0.00%)	0	2/209 (0.96%)	2	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Ligament sprain † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Limb injury † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	1	0/209 (0.00%)	0
Skeletal injury † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
Tendon injury † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
Thermal burn † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	1	0/209 (0.00%)	0
Tibia fracture † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Vertebral injury † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	1	0/209 (0.00%)	0
Wound † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	2	0/216 (0.00%)	0	0/209 (0.00%)	0
Investigations
Arthroscopy † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	1	0/209 (0.00%)	0
Blood creatine phosphokinase increased † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Cardiac murmur † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Gamma-glutamyltransferase increased † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Heart rate abnormal † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Heart rate irregular † 1	0/212 (0.00%)	0	1/209 (0.48%)	2	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Hepatic enzyme increased † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
Prostatic specific antigen increased † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	1	0/209 (0.00%)	0
Weight increased † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Metabolism and nutrition disorders
Decreased appetite † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
Gout † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	3/212 (1.42%)	3	1/216 (0.46%)	1	0/209 (0.00%)	0
Hypercholesterolaemia † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	1/212 (0.47%)	1	0/216 (0.00%)	0	1/209 (0.48%)	1
Hyperkalaemia † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Hyperlipidaemia † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	2/209 (0.96%)	2
Hyponatraemia † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Obesity † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Podagra † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	1/209 (0.48%)	1
Arthritis † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Back pain † 1	1/212 (0.47%)	1	3/209 (1.44%)	3	2/212 (0.94%)	3	10/216 (4.63%)	10	11/209 (5.26%)	13
Bone pain † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Bursitis † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Exostosis † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	1	0/209 (0.00%)	0
Intervertebral disc protrusion † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	2/216 (0.93%)	2	0/209 (0.00%)	0
Joint stiffness † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Joint swelling † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Limb discomfort † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Muscle spasms † 1	0/212 (0.00%)	0	2/209 (0.96%)	2	0/212 (0.00%)	0	2/216 (0.93%)	2	5/209 (2.39%)	6
Musculoskeletal chest pain † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	1	0/209 (0.00%)	0
Musculoskeletal pain † 1	2/212 (0.94%)	2	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	1/209 (0.48%)	1
Musculoskeletal stiffness † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Myalgia † 1	0/212 (0.00%)	0	3/209 (1.44%)	4	3/212 (1.42%)	3	6/216 (2.78%)	6	6/209 (2.87%)	7
Osteoarthritis † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
Pain in extremity † 1	0/212 (0.00%)	0	3/209 (1.44%)	5	5/212 (2.36%)	5	2/216 (0.93%)	2	3/209 (1.44%)	3
Rotator cuff syndrome † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
Spinal osteoarthritis † 1	1/212 (0.47%)	1	1/209 (0.48%)	1	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
Tendonitis † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bile duct cancer † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Nervous system disorders
Burning sensation † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	1	1/209 (0.48%)	1
Dizziness † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	1/212 (0.47%)	1	1/216 (0.46%)	1	3/209 (1.44%)	3
Headache † 1	6/212 (2.83%)	6	5/209 (2.39%)	5	6/212 (2.83%)	7	11/216 (5.09%)	11	7/209 (3.35%)	8
Hypoaesthesia † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
Lethargy † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	1	0/209 (0.00%)	0
Nerve compression † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Neuralgia † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Neuropathy peripheral † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Paraesthesia † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Sciatica † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	1/209 (0.48%)	1
Somnolence † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Syncope † 1	0/212 (0.00%)	0	2/209 (0.96%)	3	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Psychiatric disorders
Anxiety † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	1	0/209 (0.00%)	0
Depression † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	2/212 (0.94%)	2	1/216 (0.46%)	1	0/209 (0.00%)	0
Insomnia † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	2/216 (0.93%)	2	0/209 (0.00%)	0
Sleep disorder † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Renal and urinary disorders
Bladder spasm † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Dysuria † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	1/212 (0.47%)	1	0/216 (0.00%)	0	1/209 (0.48%)	1
Nocturia † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	1/216 (0.46%)	1	1/209 (0.48%)	1
Pollakiuria † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	1/209 (0.48%)	1
Renal cyst † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Urinary hesitation † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Urine flow decreased † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
Reproductive system and breast disorders
Balanitis † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
Breast pain † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	2	0/209 (0.00%)	0
Gynaecomastia † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Painful erection † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Asthma † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	1	0/209 (0.00%)	0
Cough † 1	1/212 (0.47%)	1	3/209 (1.44%)	3	2/212 (0.94%)	2	2/216 (0.93%)	2	0/209 (0.00%)	0
Dyspnoea † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	2/212 (0.94%)	2	0/216 (0.00%)	0	1/209 (0.48%)	1
Epistaxis † 1	0/212 (0.00%)	0	2/209 (0.96%)	2	2/212 (0.94%)	2	1/216 (0.46%)	1	0/209 (0.00%)	0
Nasal congestion † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	2/212 (0.94%)	2	2/216 (0.93%)	2	0/209 (0.00%)	0
Pharyngolaryngeal pain † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Pleurisy † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Rhinorrhoea † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Sinus congestion † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
Sneezing † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Throat irritation † 1	2/212 (0.94%)	2	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Skin and subcutaneous tissue disorders
Dermatitis † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Eczema † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
Photosensitivity reaction † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Pruritus † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	4	0/216 (0.00%)	0	1/209 (0.48%)	1
Rash † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	2/209 (0.96%)	2
Skin irritation † 1	2/212 (0.94%)	2	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Surgical and medical procedures
Carpal tunnel decompression † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	0/216 (0.00%)	0	1/209 (0.48%)	1
Dental operation † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	1	0/209 (0.00%)	0
Sinus operation † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Tooth extraction † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	1/212 (0.47%)	1	0/216 (0.00%)	0	1/209 (0.48%)	1
Umbilical hernia repair † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	0/212 (0.00%)	0	1/216 (0.46%)	1	0/209 (0.00%)	0
Vascular disorders
Blood pressure fluctuation † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
Flushing † 1	0/212 (0.00%)	0	1/209 (0.48%)	1	0/212 (0.00%)	0	0/216 (0.00%)	0	0/209 (0.00%)	0
Hot flush † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
Hypertension † 1	1/212 (0.47%)	1	0/209 (0.00%)	0	4/212 (1.89%)	4	1/216 (0.46%)	1	0/209 (0.00%)	0
Hypotension † 1	0/212 (0.00%)	0	0/209 (0.00%)	0	1/212 (0.47%)	1	0/216 (0.00%)	0	0/209 (0.00%)	0
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 10.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Chief Medical Officer
• Organization: Eli Lilly and Company
• Phone: 1-800-545-5979

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Vlachopoulos C, Oelke M, Maggi M, Mulhall JP, Rosenberg MT, Brock GB, Esler A, Buttner H. Impact of cardiovascular risk factors and related comorbid conditions and medical therapy reported at baseline on the treatment response to tadalafil 5 mg once-daily in men with lower urinary tract symptoms associated with benign prostatic hyperplasia: an integrated analysis of four randomised, double-blind, placebo-controlled, clinical trials. Int J Clin Pract. 2015 Dec;69(12):1496-507. doi: 10.1111/ijcp.12722. Epub 2015 Aug 24.

Broderick GA, Brock GB, Roehrborn CG, Watts SD, Elion-Mboussa A, Viktrup L. Effects of tadalafil on lower urinary tract symptoms secondary to benign prostatic hyperplasia in men with or without erectile dysfunction. Urology. 2010 Jun;75(6):1452-8. doi: 10.1016/j.urology.2009.09.093. Epub 2010 Feb 16.

Porst H, McVary KT, Montorsi F, Sutherland P, Elion-Mboussa A, Wolka AM, Viktrup L. Effects of once-daily tadalafil on erectile function in men with erectile dysfunction and signs and symptoms of benign prostatic hyperplasia. Eur Urol. 2009 Oct;56(4):727-35. doi: 10.1016/j.eururo.2009.04.033. Epub 2009 Apr 22. Erratum In: Eur Urol. 2011 Jun;59(6):1082.

Roehrborn CG, McVary KT, Elion-Mboussa A, Viktrup L. Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a dose finding study. J Urol. 2008 Oct;180(4):1228-34. doi: 10.1016/j.juro.2008.06.079. Epub 2008 Aug 22.

• Responsible Party: Chief Medical Officer, Eli Lilly
• ClinicalTrials.gov Identifier: NCT00384930
• Other Study ID Numbers: 9797; H6D-MC-LVHG
• First Submitted: October 3, 2006
• First Posted: October 6, 2006
• Results First Submitted: October 17, 2008
• Results First Posted: August 19, 2009
• Last Update Posted: September 2, 2009