Study to Treat Patients Who Have Signs and Symptoms of Benign Prostatic Hyperplasia (BPH) With Tadalafil Daily

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00827242
• Collaborator: (none)
• Enrollment: 325
• Locations: 27
• Arms: 2
• Duration (Months): 10
• Patients Per Site: 12
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether an experimental drug known as tadalafil given once daily can reduce the symptoms associated with Benign Prostatic Hyperplasia (straining, urinary frequency, feeling like your bladder is still full, etc.)

Condition or Disease	Intervention/Treatment	Phase
Benign Prostatic Hyperplasia	Drug: Placebo; Drug: tadalafil	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 325 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multinational Study to Evaluate the Efficacy and Safety of Daily Tadalafil for 12 Weeks in Men With Signs and Symptoms of Benign Prostatic Hyperplasia
• Study Start Date: Jan 1, 2009
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Nov 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tadalafil	Drug: tadalafil; Following a 4-week placebo lead-in period, subjects received tadalafil 5 mg tablet by mouth once daily over a 12-week period.; Other Names: Cialis LY450190
Placebo Comparator: Placebo	Drug: Placebo; Following a 4-week placebo lead-in period, subjects received placebo tablet by mouth once daily over a 12-week period.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) [Baseline, 12 weeks]

   The IPSS Total Score is obtained by combining the scores of the responses to Question 1 through Question 7. Each question is scored from 0-5 for a total IPSS range of 0-35 points; higher numerical scores from the IPSS questionnaire represent greater severity of symptoms. Least squares (LS) mean of change from baseline to endpoint is from an analysis of covariance (ANCOVA). The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction.

Secondary Outcome Measures

1. Change From Baseline to 4 Weeks, Benign Prostatic Hyperplasia (BPH) Impact Index [Baseline, 4 weeks]

   The BPH Impact Index (BII) is a 4-item, self-administered questionnaire evaluating impact of urinary problems on overall health and activity. Total scores range from 0 to 13; higher scores represent increased perceived impact of benign prostatic hyperplasia-lower urinary tract symptoms on overall health. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction.

2. Change From Baseline to 12 Weeks, Benign Prostatic Hyperplasia (BPH) Impact Index [Baseline, 12 weeks]

   The BII is a 4-item, self-administered questionnaire evaluating impact of urinary problems on overall health and activity. Total scores range from 0 to 13; higher scores represent increased perceived impact of benign prostatic hyperplasia-lower urinary tract symptoms on overall health. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction.

3. Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore [Baseline, 12 weeks]

   IPSS irritative subscore is the sum of Questions 2, 4 and 7 of the IPSS questionnaire. Scores range from 0 (few irritative symptoms) to 5 (frequent irritative symptoms), thus the 3 questions of the irritative subscore range from 0 to 15. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction.

4. Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore [Baseline, 12 weeks]

   IPSS obstructive subscore is the sum of Questions 1, 3, 5 and 6 of the IPSS questionnaire. Scores range from 0 (few obstructive symptoms) to 5 (frequent obstructive symptoms), thus the 4 questions of the obstructive score range from 0 to 20. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction.

5. Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Nocturia Question [Baseline, 12 weeks]

   Measures nocturia (the need to get up at night to urinate). Scores range from 0 (few episodes of nocturia) to 5 (frequent episodes of nocturia). LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction.

6. Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index [Baseline, 12 weeks]

   Assessment of QoL by urinary symptoms, with scores ranging from 0 (delighted) to 6 (terrible). LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction.

7. Patient Global Impression of Improvement (PGI-I), Number of Participants in 7 Response Categories [12 weeks]

   A scale that measures the patient's perception of improvement at the time of assessment compared with the start of treatment. The score ranges from 1 (very much better) to 7 (very much worse).

8. Clinical Global Impression of Improvement (CGI-I), Number of Participants in 7 Response Categories [12 weeks]

   Measures clinician's perception of patient improvement at the time of assessment compared with the start of treatment. Scores range from 1 (very much better) to 7 (very much worse).

9. Change From Baseline to 1 Week, International Prostate Symptom Score (IPSS) [Baseline, 1 week]

   The IPSS Total Score is obtained by combining the scores of the responses to Question 1 through Question 7. Each question is scored from 0-5 for a total IPSS range of 0-35 points; higher numerical scores from the IPSS questionnaire represent greater severity of symptoms. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction.

10. Change From Baseline to 4 Weeks, International Prostate Symptom Score (IPSS) [Baseline, 4 Weeks]

    The IPSS Total Score is obtained by combining the scores of the responses to Question 1 through Question 7. Each question is scored from 0-5 for a total IPSS range of 0-35 points; higher numerical scores from the IPSS questionnaire represent greater severity of symptoms. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction.

11. Change From Baseline to 12 Weeks, International Index of Erectile Function (IIEF)- Erectile Function (EF) Domain Scores [Baseline, 12 weeks]

    Self-reported EF. Scores range from 0 (low or no EF) to 5 (high EF) on 6 questions (1-5, 15 of the IIEF). EF Domain scores range from 0 to 30. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction.

12. Change From Baseline to 12 Weeks, Peak Flow Rate (Qmax) by Uroflowmetry [Baseline, 12 weeks]

    Qmax was defined as the peak urine flow rate (measured in milliliters per second [mL/sec] using standard calibrated flowmeter). At each visit, a uroflowmetry assessment was considered valid and the data were included in the statistical analyses only if the prevoid total bladder volume (assessed by ultrasound) was >=150 to <=550 milliliters (mL) and the voided volume (Vcomp) was >=125 mL.

13. Change From Baseline to 12 Weeks, Mean Flow Rate (Qmean) by Uroflowmetry [Baseline, 12 weeks]

    Qmean was defined as the mean urine flow rate (measured in mL/sec using standard calibrated flowmeter). At each visit, a uroflowmetry assessment was considered valid and the data were included in the statistical analyses only if the prevoid total bladder volume (assessed by ultrasound) was >=150 to <=550 mL and the Vcomp was >=125 mL.

14. Change From Baseline to 12 Weeks, Voided Volume (Vcomp) by Uroflowmetry [Baseline, 12 weeks]

    Vcomp was defined as the volume of urine voided (measured in mL using standard calibrated flowmeter). At each visit, a uroflowmetry assessment was considered valid and the data were included in the statistical analyses only if the prevoid total bladder volume (assessed by ultrasound) was >=150 to <=550 mL and the Vcomp was >=125 mL.

15. Change From Baseline to 12 Weeks, Postvoid Residual (PVR) Volume [Baseline, 12 weeks]

    The amount of urine remaining in the bladder after void completion.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Men 45 years of age or older with Benign Prostatic Hyperplasia (BPH) also referred to as BPH-LUTS [lower urinary tract symptoms] based on the disease diagnostic criteria at the start of study.

• Provide signed informed consent at the start of the study.

• Have not taken Finasteride therapy for at least 3 months before study drug is dispensed and Dutasteride therapy for at least 6 months before study drug is dispensed.

• Have not taken other BPH therapy (including herbal preparations), overactive bladder (OAB) therapy, or erectile dysfunction (ED) therapy for at least 4 weeks prior to study drug is dispensed.

• Agree not to use any other approved or experimental pharmacologic BPH, OAB, or ED treatments anytime during the study

• Have LUTS with a Total International Prostate Symptom Score (IPSS) greater than or equal to 13 when study drug is dispensed.

• Have reduced peak urine flow rate when study drug is dispensed (measured by a special toilet equipment).

• Demonstrate compliance with study drug administration requirements.

Exclusion Criteria:

• Treated with nitrates for a cardiac conditions.

• Have unstable angina or angina that requires treatment.

• Have had any of the following in the past 90 days: Heart attack, also known as a myocardial infarction (MI); Heart bypass surgery (called coronary artery bypass graft surgery); Had a procedure to open up blood vessels in the heart known as angioplasty or stent placement (percutaneous coronary intervention).

• Have very high or very low blood pressure

• Have problems with kidneys, liver, or nervous system.

• Have uncontrolled diabetes.

• Have had a stroke or a significant injury to brain or spinal cord.

• Have prostate cancer, are being treated for cancer or have clinical evidence of prostate cancer (Prostate-Specific Antigen [PSA] greater than 10 nanograms/milliliter [ng/ml] at the start of study).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Huntsville	Alabama	United States	35801
2	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Middlebury	Connecticut	United States	06762
3	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Sarasota	Florida	United States	34237
4	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Roswell	Georgia	United States	30076
5	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Chicago	Illinois	United States	60611
6	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bayshore	New York	United States	11706
7	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	New York	New York	United States	10016
8	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Williamsville	New York	United States	14221
9	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Durham	North Carolina	United States	27710
10	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Columbus	Ohio	United States	43220
11	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Knoxville	Tennessee	United States	37920
12	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Virginia Beach	Virginia	United States	23454
13	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Buenos Aires		Argentina	1405
14	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Berlin		Germany	13465
15	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hamburg		Germany	20354
16	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Marburg		Germany	35039
17	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Muehlacker		Germany	D-75417
18	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Oranienburg		Germany	D-16515
19	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bergamo		Italy	24128
20	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Milan		Italy	20132
21	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Napoli		Italy	80131
22	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Orbassano		Italy	10043
23	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Rome		Italy	00161
24	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Mexico City		Mexico	10700
25	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Monterrey		Mexico	64040
26	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Saltillo		Mexico	25210
27	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Zapopan		Mexico	45040

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern Time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00827242
• Other Study ID Numbers: 10893; H6D-MC-LVHJ
• First Posted: Jan 22, 2009
• Last Update Posted: Nov 17, 2010
• Last Verified: Oct 1, 2010

• Keywords provided by , ,: Signs and Symptoms; Prostatic Hyperplasia; Hyperplasia; Genital Diseases, Male; Prostatic Diseases; BPH-LUTS
• Additional relevant MeSH terms: Prostatic Hyperplasia; Hyperplasia; Tadalafil

Study Results

Participant Flow

Arm/Group Title	Tadalafil	Placebo
Arm/Group Description	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive tadalafil 5 mg orally once daily over a 12-week period.	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive placebo orally once daily over a 12-week period.
Period Title: Overall Study
STARTED	161	164
COMPLETED	148	152
NOT COMPLETED	13	12

Baseline Characteristics

Arm/Group Title	Tadalafil	Placebo	Total
Arm/Group Description	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive tadalafil 5 mg orally once daily over a 12-week period.	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive placebo orally once daily over a 12-week period.	Total of all reporting groups
Overall Participants	161	164	325
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.1 (8.43)	64.6 (10.03)	64.9 (9.26)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	161 100%	164 100%	325 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	46 28.6%	44 26.8%	90 27.7%
Not Hispanic or Latino	115 71.4%	120 73.2%	235 72.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	9 5.6%	8 4.9%	17 5.2%
Asian	2 1.2%	0 0%	2 0.6%
Black or African American	3 1.9%	5 3%	8 2.5%
White	146 90.7%	150 91.5%	296 91.1%
More than one race	1 0.6%	1 0.6%	2 0.6%
Region of Enrollment (participants) [Number]
United States	50 31.1%	52 31.7%	102 31.4%
South America	43 26.7%	43 26.2%	86 26.5%
Europe	68 42.2%	69 42.1%	137 42.2%
Body Mass Index (BMI) (kilogram (kg)/meter (m)^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram (kg)/meter (m)^2]	27.1 (3.82)	28.4 (4.21)	27.7 (4.07)
Baseline Lower Urinary Tract Symptoms (LUTS) Severity (participants) [Number]
Moderate	100 62.1%	110 67.1%	210 64.6%
Severe	61 37.9%	54 32.9%	115 35.4%
Peak Urine Flow Rate (Qmax) Category (participants) [Number]
<10 mL/sec	54 33.5%	62 37.8%	116 35.7%
10-15 mL/sec	78 48.4%	67 40.9%	145 44.6%
>15 mL/sec	20 12.4%	24 14.6%	44 13.5%
Post-void Residual Volume (PVR) (mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL]	44.9 (44.87)	63.3 (59.88)	54.2 (53.70)
Prostate-Specific Antigen (PSA) (ng/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/mL]	2.0 (1.75)	2.2 (1.72)	2.1 (1.74)
Erectile Dysfunction (ED) (participants) [Number]
Yes	112 69.6%	112 68.3%	224 68.9%
No	49 30.4%	52 31.7%	101 31.1%
ED Severity (participants) [Number]
Mild	34 21.1%	40 24.4%	74 22.8%
Moderate	61 37.9%	59 36%	120 36.9%
Severe	17 10.6%	13 7.9%	30 9.2%
ED Duration (participants) [Number]
<1 year	14 8.7%	17 10.4%	31 9.5%
>=1 year	98 60.9%	95 57.9%	193 59.4%
Sexually Active with a Female Partner (participants) [Number]
Yes	128 79.5%	129 78.7%	257 79.1%
No	33 20.5%	35 21.3%	68 20.9%
Expect to Remain Sexually Active (participants) [Number]
Yes	127 78.9%	129 78.7%	256 78.8%
No	1 0.6%	0 0%	1 0.3%
Patient Global Impression of Severity (PGI-S) (participants) [Number]
Normal	5 3.1%	8 4.9%	13 4%
Mild	35 21.7%	27 16.5%	62 19.1%
Moderate	102 63.4%	105 64%	207 63.7%
Severe	19 11.8%	24 14.6%	43 13.2%
Clinician Global Impression of Severity (CGI-S) (participants) [Number]
Normal	0 0%	1 0.6%	1 0.3%
Mild	36 22.4%	37 22.6%	73 22.5%
Moderate	104 64.6%	95 57.9%	199 61.2%
Severe	21 13%	31 18.9%	52 16%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS)
Description	The IPSS Total Score is obtained by combining the scores of the responses to Question 1 through Question 7. Each question is scored from 0-5 for a total IPSS range of 0-35 points; higher numerical scores from the IPSS questionnaire represent greater severity of symptoms. Least squares (LS) mean of change from baseline to endpoint is from an analysis of covariance (ANCOVA). The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

The analysis population was defined as all subjects who were randomized, started study medication, and had non-missing data at baseline and at least one post-baseline visit. The Last Observation Carried Forward (LOCF) imputation technique was employed.

Arm/Group Title	Tadalafil	Placebo
Arm/Group Description	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive tadalafil 5 mg orally once daily over a 12-week period.	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive placebo orally once daily over a 12-week period.
Measure Participants	160	164
Least Squares Mean (Standard Error) [Units on a Scale]	-5.6 (0.47)	-3.6 (0.47)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tadalafil, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments	The p-value associates with LS Mean difference of changes from baseline to 12 weeks between treatment groups for IPSS. Under the pre-specified fixed sequence testing procedure, the significance level of 0.05 is used for assessment.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.9
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.66
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline to 4 Weeks, Benign Prostatic Hyperplasia (BPH) Impact Index
Description	The BPH Impact Index (BII) is a 4-item, self-administered questionnaire evaluating impact of urinary problems on overall health and activity. Total scores range from 0 to 13; higher scores represent increased perceived impact of benign prostatic hyperplasia-lower urinary tract symptoms on overall health. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction.
Time Frame	Baseline, 4 weeks

Outcome Measure Data

Analysis Population Description

The analysis population includes all subjects who were randomized, started study medication, and had non-missing data at baseline and Week 4.

Arm/Group Title	Tadalafil	Placebo
Arm/Group Description	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive tadalafil 5 mg orally once daily over a 12-week period.	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive placebo orally once daily over a 12-week period.
Measure Participants	158	162
Least Squares Mean (Standard Error) [Units on a Scale]	-1.8 (0.18)	-1.2 (0.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tadalafil, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.029
	Comments	The p-value associates with LS Mean difference of changes from baseline to 4 weeks between treatment groups for BII. Under the pre-specified fixed sequence testing procedure, the significance level of 0.05 is used for assessment.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.6
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.26
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline to 12 Weeks, Benign Prostatic Hyperplasia (BPH) Impact Index
Description	The BII is a 4-item, self-administered questionnaire evaluating impact of urinary problems on overall health and activity. Total scores range from 0 to 13; higher scores represent increased perceived impact of benign prostatic hyperplasia-lower urinary tract symptoms on overall health. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

The analysis population includes all subjects who were randomized, started study medication, and had non-missing data at baseline and Week 12. For the 12 week analysis, the LOCF imputation technique was used.

Arm/Group Title	Tadalafil	Placebo
Arm/Group Description	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive tadalafil 5 mg orally once daily over a 12-week period.	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive placebo orally once daily over a 12-week period.
Measure Participants	160	163
Least Squares Mean (Standard Error) [Units on a Scale]	-1.8 (0.21)	-1.3 (0.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tadalafil, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.057
	Comments	The p-value associates with LS Mean difference of changes from baseline to 12 weeks between treatment groups for BII. Under the pre-specified fixed sequence testing procedure, the significance level of 0.05 is used for assessment.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.6
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.3
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore
Description	IPSS irritative subscore is the sum of Questions 2, 4 and 7 of the IPSS questionnaire. Scores range from 0 (few irritative symptoms) to 5 (frequent irritative symptoms), thus the 3 questions of the irritative subscore range from 0 to 15. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

The analysis population was defined as all randomized subjects who started study medication, and had non-missing data at baseline and at least one post-baseline measurement. The LOCF imputation technique was employed.

Arm/Group Title	Tadalafil	Placebo
Arm/Group Description	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive tadalafil 5 mg orally once daily over a 12-week period.	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive placebo orally once daily over a 12-week period.
Measure Participants	160	164
Least Squares Mean (Standard Error) [Units on a Scale]	-2.3 (0.22)	-1.3 (0.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tadalafil, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments	The p-value associates with LS Mean difference of changes from baseline to 12 weeks between treatment groups for IPSS storage subscore. Under the pre-specified fixed sequence testing procedure, the significance level of 0.05 is used for assessment.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.9
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.30
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore
Description	IPSS obstructive subscore is the sum of Questions 1, 3, 5 and 6 of the IPSS questionnaire. Scores range from 0 (few obstructive symptoms) to 5 (frequent obstructive symptoms), thus the 4 questions of the obstructive score range from 0 to 20. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

The analysis population was defined as all randomized subjects who started study medication, and had non-missing data at baseline and at least one post-baseline measurement. The LOCF imputation technique was employed.

Arm/Group Title	Tadalafil	Placebo
Arm/Group Description	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive tadalafil 5 mg orally once daily over a 12-week period.	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive placebo orally once daily over a 12-week period.
Measure Participants	160	164
Least Squares Mean (Standard Error) [Units on a Scale]	-3.3 (0.31)	-2.3 (0.31)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tadalafil, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.020
	Comments	The p-value associates with LS Mean difference of changes from baseline to 12 weeks between treatment groups for IPSS voiding subscore. Under the pre-specified fixed sequence testing procedure, the significance level of 0.05 is used for assessment.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.0
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.43
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Nocturia Question
Description	Measures nocturia (the need to get up at night to urinate). Scores range from 0 (few episodes of nocturia) to 5 (frequent episodes of nocturia). LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

The analysis population was defined as all randomized subjects who started study medication, and had non-missing data at baseline and at least one post-baseline measurement. The LOCF imputation technique was employed.

Arm/Group Title	Tadalafil	Placebo
Arm/Group Description	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive tadalafil 5 mg orally once daily over a 12-week period.	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive placebo orally once daily over a 12-week period.
Measure Participants	160	164
Least Squares Mean (Standard Error) [Units on a Scale]	-0.5 (0.08)	-0.4 (0.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tadalafil, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.233
	Comments	The p-value associates with LS Mean difference of changes from baseline to 12 weeks between treatment groups for IPSS nocturia question. Under the pre-specified fixed sequence testing procedure, the significance level of 0.05 is used for assessment.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.1
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index
Description	Assessment of QoL by urinary symptoms, with scores ranging from 0 (delighted) to 6 (terrible). LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

The analysis population was defined as all randomized subjects who started study medication, and had non-missing data at baseline and at least one post-baseline measurement. The LOCF imputation technique was employed.

Arm/Group Title	Tadalafil	Placebo
Arm/Group Description	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive tadalafil 5 mg orally once daily over a 12-week period.	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive placebo orally once daily over a 12-week period.
Measure Participants	160	164
Least Squares Mean (Standard Error) [Units on a Scale]	-1.0 (0.10)	-0.7 (0.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tadalafil, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.013
	Comments	The p-value associates with LS Mean difference of changes from baseline to 12 weeks between treatment groups for IPSS QoL Index. Under the pre-specified fixed sequence testing procedure, the significance level of 0.05 is used for assessment.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.4
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments

8. Secondary Outcome

Title	Patient Global Impression of Improvement (PGI-I), Number of Participants in 7 Response Categories
Description	A scale that measures the patient's perception of improvement at the time of assessment compared with the start of treatment. The score ranges from 1 (very much better) to 7 (very much worse).
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

The analysis population includes all subjects who were randomized, started study medication, and had non-missing data.

Arm/Group Title	Tadalafil	Placebo
Arm/Group Description	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive tadalafil 5 mg orally once daily over a 12-week period.	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive placebo orally once daily over a 12-week period.
Measure Participants	155	158
7-Very Much Worse	1 0.6%	0 0%
6-Much Worse	5 3.1%	6 3.7%
5-A Little Worse	4 2.5%	4 2.4%
4-No Change	30 18.6%	57 34.8%
3-A Little Better	57 35.4%	53 32.3%
2-Much Better	46 28.6%	32 19.5%
1-Very Much Better	12 7.5%	6 3.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tadalafil, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.021
	Comments	The p-value associates with difference between treatment groups for the 7 response categories.
	Method	Cochran-Mantel-Haenszel
	Comments	Results were adjusted for baseline LUTS severity (moderate [total IPSS < 20]; severe [total IPSS >= 20]

9. Secondary Outcome

Title	Clinical Global Impression of Improvement (CGI-I), Number of Participants in 7 Response Categories
Description	Measures clinician's perception of patient improvement at the time of assessment compared with the start of treatment. Scores range from 1 (very much better) to 7 (very much worse).
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

All values are based on the number of subjects in the analysis population with non-missing data.

Arm/Group Title	Tadalafil	Placebo
Arm/Group Description	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive tadalafil 5 mg orally once daily over a 12-week period.	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive placebo orally once daily over a 12-week period.
Measure Participants	155	158
7-Very Much Worse	0 0%	0 0%
6-Much Worse	5 3.1%	2 1.2%
5-A Little Worse	4 2.5%	10 6.1%
4-No Change	36 22.4%	59 36%
3-A Little Better	58 36%	55 33.5%
2-Much Better	39 24.2%	25 15.2%
1-Very Much Better	13 8.1%	7 4.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tadalafil, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.009
	Comments	The p-value associates with difference between treatment groups for the 7 response categories.
	Method	Cochran-Mantel-Haenszel
	Comments	Results were adjusted for baseline LUTS severity (moderate [total IPSS < 20]; severe [total IPSS >= 20]

10. Secondary Outcome

Title	Change From Baseline to 1 Week, International Prostate Symptom Score (IPSS)
Description	The IPSS Total Score is obtained by combining the scores of the responses to Question 1 through Question 7. Each question is scored from 0-5 for a total IPSS range of 0-35 points; higher numerical scores from the IPSS questionnaire represent greater severity of symptoms. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction.
Time Frame	Baseline, 1 week

Outcome Measure Data

Analysis Population Description

The analysis population includes all subjects who were randomized, started study medication, and had non-missing data at baseline and Week 1.

Arm/Group Title	Tadalafil	Placebo
Arm/Group Description	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive tadalafil 5 mg orally once daily over a 12-week period.	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive placebo orally once daily over a 12-week period.
Measure Participants	147	150
Least Squares Mean (Standard Error) [Units on a Scale]	-3.4 (0.35)	-2.7 (0.35)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tadalafil, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.146
	Comments	The p-value associates with LS Mean difference of changes from baseline to 1 week between treatment groups for IPSS. Under the pre-specified fixed sequence testing procedure, the significance level of 0.05 is used for assessment.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.7
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.49
	Estimation Comments

11. Secondary Outcome

Title	Change From Baseline to 4 Weeks, International Prostate Symptom Score (IPSS)
Description	The IPSS Total Score is obtained by combining the scores of the responses to Question 1 through Question 7. Each question is scored from 0-5 for a total IPSS range of 0-35 points; higher numerical scores from the IPSS questionnaire represent greater severity of symptoms. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction.
Time Frame	Baseline, 4 Weeks

Outcome Measure Data

Analysis Population Description

The analysis population includes all subjects who were randomized, started study medication, and had non-missing data at baseline and Week 4.

Arm/Group Title	Tadalafil	Placebo
Arm/Group Description	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive tadalafil 5 mg orally once daily over a 12-week period.	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive placebo orally once daily over a 12-week period.
Measure Participants	158	162
Least Squares Mean (Standard Error) [Units on a Scale]	-5.3 (0.43)	-3.5 (0.43)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tadalafil, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments	The p-value associates with LS Mean difference of changes from baseline to 4 weeks between treatment groups for IPSS. Under the pre-specified fixed sequence testing procedure, the significance level of 0.05 is used for assessment.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.8
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.60
	Estimation Comments

12. Secondary Outcome

Title	Change From Baseline to 12 Weeks, International Index of Erectile Function (IIEF)- Erectile Function (EF) Domain Scores
Description	Self-reported EF. Scores range from 0 (low or no EF) to 5 (high EF) on 6 questions (1-5, 15 of the IIEF). EF Domain scores range from 0 to 30. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

The analysis population was defined as all randomized subjects who started study medication, and had non-missing data at baseline and at least one post-baseline measurement. Measures were taken only for those subjects who reported they were sexually active and reported erectile dysfunction. The LOCF imputation technique was employed.

Arm/Group Title	Tadalafil	Placebo
Arm/Group Description	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive tadalafil 5 mg orally once daily over a 12-week period.	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive placebo orally once daily over a 12-week period.
Measure Participants	88	84
Least Squares Mean (Standard Error) [Units on a Scale]	6.7 (0.80)	2.0 (0.82)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tadalafil, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	The p-value associates with LS Mean difference of changes from baseline to 12 weeks between treatment groups for IIEF-EF domain score. Under the pre-specified fixed sequence testing procedure, the significance level of 0.05 is used for assessment.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	4.7
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.12
	Estimation Comments

13. Secondary Outcome

Title	Change From Baseline to 12 Weeks, Peak Flow Rate (Qmax) by Uroflowmetry
Description	Qmax was defined as the peak urine flow rate (measured in milliliters per second [mL/sec] using standard calibrated flowmeter). At each visit, a uroflowmetry assessment was considered valid and the data were included in the statistical analyses only if the prevoid total bladder volume (assessed by ultrasound) was >=150 to <=550 milliliters (mL) and the voided volume (Vcomp) was >=125 mL.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

The analysis population was defined as all randomized subjects who started study medication, and had non-missing data at baseline and at endpoint (considered the last non-missing post-baseline value).

Arm/Group Title	Tadalafil	Placebo
Arm/Group Description	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive tadalafil 5 mg orally once daily over a 12-week period.	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive placebo orally once daily over a 12-week period.
Measure Participants	127	135
Mean (Standard Deviation) [mL/sec]	1.6 (4.64)	1.1 (4.64)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tadalafil, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.300
	Comments	The p-value associates with mean difference of changes from baseline to 12 weeks between treatment groups for Qmax. Under the pre-specified fixed sequence testing procedure, the significance level of 0.05 is used for assessment.
	Method	ranked ANOVA
	Comments

14. Secondary Outcome

Title	Change From Baseline to 12 Weeks, Mean Flow Rate (Qmean) by Uroflowmetry
Description	Qmean was defined as the mean urine flow rate (measured in mL/sec using standard calibrated flowmeter). At each visit, a uroflowmetry assessment was considered valid and the data were included in the statistical analyses only if the prevoid total bladder volume (assessed by ultrasound) was >=150 to <=550 mL and the Vcomp was >=125 mL.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

The analysis population was defined as all randomized subjects who started study medication, and had non-missing data at baseline and at endpoint (considered the last non-missing post-baseline value).

Arm/Group Title	Tadalafil	Placebo
Arm/Group Description	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive tadalafil 5 mg orally once daily over a 12-week period.	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive placebo orally once daily over a 12-week period.
Measure Participants	127	135
Mean (Standard Deviation) [mL/sec]	0.6 (2.93)	0.5 (2.79)

15. Secondary Outcome

Title	Change From Baseline to 12 Weeks, Voided Volume (Vcomp) by Uroflowmetry
Description	Vcomp was defined as the volume of urine voided (measured in mL using standard calibrated flowmeter). At each visit, a uroflowmetry assessment was considered valid and the data were included in the statistical analyses only if the prevoid total bladder volume (assessed by ultrasound) was >=150 to <=550 mL and the Vcomp was >=125 mL.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

The analysis population was defined as all randomized subjects who started study medication, and had non-missing data at baseline and at endpoint (considered the last non-missing post-baseline value).

Arm/Group Title	Tadalafil	Placebo
Arm/Group Description	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive tadalafil 5 mg orally once daily over a 12-week period.	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive placebo orally once daily over a 12-week period.
Measure Participants	127	135
Mean (Standard Deviation) [mL]	16.9 (88.74)	3.9 (105.68)

16. Secondary Outcome

Title	Change From Baseline to 12 Weeks, Postvoid Residual (PVR) Volume
Description	The amount of urine remaining in the bladder after void completion.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

The analysis population was defined as all randomized subjects who started study medication, and had non-missing data at baseline and at endpoint (considered the last non-missing post-baseline value).

Arm/Group Title	Tadalafil	Placebo
Arm/Group Description	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive tadalafil 5 mg orally once daily over a 12-week period.	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive placebo orally once daily over a 12-week period.
Measure Participants	154	158
Mean (Standard Deviation) [mL]	8.8 (56.40)	4.5 (66.71)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tadalafil, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.500
	Comments	The p-value associates with mean difference of changes from baseline to 12 weeks between treatment groups for PVR volume. Under the pre-specified fixed sequence testing procedure, the significance level of 0.05 is used for assessment.
	Method	ranked ANOVA
	Comments

Adverse Events

Arm/Group Title	Tadalafil		Placebo
Arm/Group Description	Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive tadalafil 5 mg orally once daily over a 12-week period.		Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive placebo orally once daily over a 12-week period.
All Cause Mortality
	Tadalafil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Tadalafil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/161 (1.2%)		0/164 (0%)
Cardiac disorders
Acute myocardial infarction	1/161 (0.6%)	1	0/164 (0%)	0
Infections and infestations
Endocarditis	1/161 (0.6%)	1	0/164 (0%)	0
Other (Not Including Serious) Adverse Events
	Tadalafil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	41/161 (25.5%)		36/164 (22%)
Cardiac disorders
Atrioventricular block first degree	0/161 (0%)	0	1/164 (0.6%)	1
Bundle branch block right	0/161 (0%)	0	1/164 (0.6%)	1
Ear and labyrinth disorders
Deafness	1/161 (0.6%)	1	0/164 (0%)	0
Ear pain	1/161 (0.6%)	1	0/164 (0%)	0
Endocrine disorders
Hypothyroidism	1/161 (0.6%)	1	1/164 (0.6%)	1
Gastrointestinal disorders
Abdominal distension	0/161 (0%)	0	1/164 (0.6%)	1
Abdominal pain upper	1/161 (0.6%)	1	1/164 (0.6%)	1
Anal fistula	0/161 (0%)	0	1/164 (0.6%)	1
Diarrhoea	1/161 (0.6%)	1	2/164 (1.2%)	2
Dyspepsia	1/161 (0.6%)	1	1/164 (0.6%)	1
Gastric disorder	0/161 (0%)	0	1/164 (0.6%)	1
Gastrooesophageal reflux disease	2/161 (1.2%)	2	0/164 (0%)	0
Haemorrhoidal haemorrhage	1/161 (0.6%)	1	0/164 (0%)	0
Nausea	0/161 (0%)	0	1/164 (0.6%)	1
Oesophagitis	0/161 (0%)	0	1/164 (0.6%)	1
Toothache	0/161 (0%)	0	1/164 (0.6%)	1
Vomiting	1/161 (0.6%)	1	1/164 (0.6%)	1
General disorders
Asthenia	1/161 (0.6%)	2	1/164 (0.6%)	2
Influenza like illness	1/161 (0.6%)	1	1/164 (0.6%)	1
Oedema peripheral	0/161 (0%)	0	1/164 (0.6%)	1
Hepatobiliary disorders
Biliary colic	1/161 (0.6%)	1	0/164 (0%)	0
Infections and infestations
Bronchitis	1/161 (0.6%)	1	0/164 (0%)	0
Gastroenteritis	1/161 (0.6%)	1	0/164 (0%)	0
Influenza	1/161 (0.6%)	1	3/164 (1.8%)	4
Nasopharyngitis	3/161 (1.9%)	3	3/164 (1.8%)	4
Sinusitis	2/161 (1.2%)	2	0/164 (0%)	0
Upper respiratory tract infection	0/161 (0%)	0	1/164 (0.6%)	1
Wound infection	1/161 (0.6%)	1	0/164 (0%)	0
Injury, poisoning and procedural complications
Arthropod bite	0/161 (0%)	0	1/164 (0.6%)	1
Fall	1/161 (0.6%)	1	0/164 (0%)	0
Incision site pain	0/161 (0%)	0	1/164 (0.6%)	1
Joint sprain	1/161 (0.6%)	1	0/164 (0%)	0
Muscle strain	1/161 (0.6%)	1	0/164 (0%)	0
Vertebral injury	1/161 (0.6%)	1	0/164 (0%)	0
Investigations
Endoscopy	0/161 (0%)	0	1/164 (0.6%)	1
Hepatic enzyme increased	1/161 (0.6%)	1	0/164 (0%)	0
Prostatic specific antigen increased	1/161 (0.6%)	1	0/164 (0%)	0
Metabolism and nutrition disorders
Dyslipidaemia	1/161 (0.6%)	1	0/164 (0%)	0
Hypertriglyceridaemia	1/161 (0.6%)	1	0/164 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	3/161 (1.9%)	3	0/164 (0%)	0
Arthritis	0/161 (0%)	0	1/164 (0.6%)	1
Back pain	5/161 (3.1%)	5	4/164 (2.4%)	4
Intervertebral disc protrusion	1/161 (0.6%)	1	0/164 (0%)	0
Myalgia	2/161 (1.2%)	2	0/164 (0%)	0
Pain in extremity	2/161 (1.2%)	2	0/164 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	1/161 (0.6%)	1	1/164 (0.6%)	1
Thyroid neoplasm	0/161 (0%)	0	1/164 (0.6%)	1
Nervous system disorders
Dizziness	3/161 (1.9%)	3	0/164 (0%)	0
Headache	6/161 (3.7%)	6	1/164 (0.6%)	1
Psychiatric disorders
Anxiety	1/161 (0.6%)	1	0/164 (0%)	0
Insomnia	2/161 (1.2%)	2	0/164 (0%)	0
Renal and urinary disorders
Dysuria	0/161 (0%)	0	1/164 (0.6%)	1
Micturition urgency	1/161 (0.6%)	1	0/164 (0%)	0
Nocturia	1/161 (0.6%)	1	0/164 (0%)	0
Urinary retention	0/161 (0%)	0	1/164 (0.6%)	1
Respiratory, thoracic and mediastinal disorders
Cough	0/161 (0%)	0	2/164 (1.2%)	2
Oropharyngeal pain	0/161 (0%)	0	2/164 (1.2%)	2
Skin and subcutaneous tissue disorders
Night sweats	1/161 (0.6%)	1	0/164 (0%)	0
Pruritus	0/161 (0%)	0	1/164 (0.6%)	1
Vascular disorders
Hypertension	3/161 (1.9%)	3	3/164 (1.8%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.