A Study in Benign Prostatic Hyperplasia

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01152190
• Collaborator: (none)
• Enrollment: 97
• Locations: 5
• Arms: 2
• Duration (Months): 22
• Patients Per Site: 19.4
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The purpose of this trial is to evaluate the effect of tadalafil 5 milligrams (mg) daily for 8 weeks compared to placebo on prostatic blood perfusion in men with signs and symptoms of Benign Prostatic Hyperplasia (BPH), measured by resistive index (RI) in the prostate transition zone.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 97 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Basic Science
• Official Title: A Randomized, Double Blind, Placebo-controlled Study to Evaluate the Effect of Tadalafil Once Daily for 8 Weeks on Prostatic Blood Flow and Perfusion Parameters in Men With Signs and Symptoms of Benign Prostatic Hyperplasia
• Study Start Date: Sep 1, 2010
• Actual Primary Completion Date: Jul 1, 2012
• Actual Study Completion Date: Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 5 milligrams (mg) Tadalafil	Drug: Tadalafil; Administered orally, once daily for 8 weeks; Other Names: Cialis LY450190
Placebo Comparator: Placebo	Drug: Placebo; Administered orally, once daily for 8 weeks

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to 8-Week Endpoint in Arterial Resistive Index (RI) in the Prostate Transition Zone [Baseline, Week 8]

   Arterial RI was a measure of vascular resistance using Doppler ultrasound. RI was the ratio of (peak systolic velocity - end diastolic velocity)/peak systolic velocity, and increased as resistance to blood flow increased. The least squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included fixed effects for treatment, region, visit, and treatment-by-visit interaction, baseline as a covariate, a random effect of participant within treatment, and an unstructured covariance matrix.

Secondary Outcome Measures

1. Change From Baseline to 4-Week Endpoint in Arterial Resistive Index (RI) in the Prostate Transition Zone [Baseline, Week 4]

   Arterial RI was a measure of vascular resistance using Doppler ultrasound. RI was the ratio of (peak systolic velocity - end diastolic velocity)/peak systolic velocity, and increased as resistance to flow increased. The least squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included fixed effects for treatment, region, visit, and treatment-by-visit interaction, baseline as a covariate, a random effect of participant within treatment, and an unstructured covariance matrix.

2. Change From Baseline to 4 and 8 Weeks in Arterial Resistive Index (RI) in the Prostate Peripheral Zone and Bladder Neck [Baseline, Week 4 and Week 8]

   Arterial RI was a measure of vascular resistance using Doppler ultrasound. RI was the ratio of (peak systolic velocity - end diastolic velocity)/peak systolic velocity, and increased as resistance to flow increased. The least squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included fixed effects for treatment, region, visit, and treatment-by-visit interaction, baseline as a covariate, a random effect of participant within treatment, and an unstructured covariance matrix.

3. Change From Baseline to 4 and 8 Weeks in Color Pixel Intensity (CPI) in the Prostate Transition Zone, Peripheral Zone, and Bladder Neck [Baseline, Week 4 and Week 8]

   CPI quantified blood flow in a pre-specified region of interest by using color Doppler imaging. CPI was the mean color pixel intensity in the region of interest and scores could range from 0 to 160. An increase in CPI reflected an increase in blood flow. The least squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included fixed effects for treatment, region, visit, and treatment-by-visit interaction, baseline as a covariate, a random effect of participant within treatment, and an unstructured covariance matrix.

Eligibility Criteria

Criteria

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

Inclusion Criteria

• Present with benign prostatic hyperplasia

• Provide signed informed consent at the screening

• Agree not to use other treatment for Benign Prostatic Hyperplasia, Erectile Dysfunction or Overactive Bladder (including herbal treatments) during the study

Exclusion Criteria

• Have prostatic cancer or are being treated for cancer.

• Any condition that may negatively influence the transrectal ultrasound.

• Are being treated for heart disease with any drug that is called a nitrate (for example, nitroglycerin).

• Any evidence of moderate to severe cardiac disease

• Have had any of the following in the past 90 days: chest pain (called unstable angina or angina) that requires treatment, heart attack also known as myocardial infarction, heart bypass surgery (called coronary artery bypass graft surgery), had a procedure to open up blood vessels in the heart know as angioplasty or stent placement (percutaneous coronary intervention), positive cardiac stress test without effective cardiac intervention.

• Have very high or very low blood pressure.

• Have uncontrolled diabetes.

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

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.	Chicago	Illinois	United States	60611
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.	Garden City	New York	United States	11530
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.	New York	New York	United States	10016
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.	Innsbruck		Austria	6020
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.	Bergamo		Italy	24128

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.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01152190
• Other Study ID Numbers: 13469; H6D-MC-LVIR
• First Posted: Jun 29, 2010
• Last Update Posted: May 20, 2013
• Last Verified: Mar 1, 2013

• Additional relevant MeSH terms: Prostatic Hyperplasia; Hyperplasia; Tadalafil

Study Results

Participant Flow

Arm/Group Title	Placebo	Tadalafil
Arm/Group Description	Placebo: tablet administered orally, once daily for 8 weeks.	Tadalafil: 5-milligram (mg) tablet administered orally, once daily for 8 weeks.
Period Title: Overall Study
STARTED	50	47
Received at Least 1 Dose of Study Drug	50	47
COMPLETED	45	39
NOT COMPLETED	5	8

Baseline Characteristics

Arm/Group Title	Placebo	Tadalafil	Total
Arm/Group Description	Placebo: tablet administered orally, once daily for 8 weeks.	Tadalafil: 5-milligram (mg) tablet administered orally, once daily for 8 weeks.	Total of all reporting groups
Overall Participants	50	47	97
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.3 (8.18)	60.0 (7.53)	60.2 (7.83)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	50 100%	47 100%	97 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	2 4.3%	2 2.1%
Not Hispanic or Latino	50 100%	45 95.7%	95 97.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 2%	2 4.3%	3 3.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	8 16%	3 6.4%	11 11.3%
White	41 82%	42 89.4%	83 85.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Austria	6 12%	7 14.9%	13 13.4%
Belgium	4 8%	5 10.6%	9 9.3%
Italy	15 30%	14 29.8%	29 29.9%
United States	25 50%	21 44.7%	46 47.4%
Erectile Dysfunction (ED) Etiology (participants) [Number]
Psychogenic	0 0%	0 0%	0 0%
Organic	18 36%	15 31.9%	33 34%
Mixed	13 26%	12 25.5%	25 25.8%
Unknown	2 4%	2 4.3%	4 4.1%
ED Severity (participants) [Number]
Mild	11 22%	9 19.1%	20 20.6%
Moderate	16 32%	15 31.9%	31 32%
Severe	6 12%	5 10.6%	11 11.3%
ED Duration (participants) [Number]
<1 year	4 8%	1 2.1%	5 5.2%
≥1 year	28 56%	28 59.6%	56 57.7%
Body Mass Index (kilograms per meter-squared (kg/m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms per meter-squared (kg/m^2)]	27.4 (3.19)	26.4 (3.28)	26.9 (3.25)
Sitting Diastolic Blood Pressure (millimeters of mercury (mm Hg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [millimeters of mercury (mm Hg)]	81.8 (8.73)	81.5 (6.85)	81.7 (7.83)
Sitting Systolic Blood Pressure (millimeters of mercury (mm Hg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [millimeters of mercury (mm Hg)]	131.0 (13.69)	131.7 (11.96)	131.4 (12.82)
Baseline Lower Urinary Tract Symptoms (LUTS) Severity (participants) [Number]
Moderate	22 44%	20 42.6%	42 43.3%
Severe	28 56%	27 57.4%	55 56.7%
Urinary Peak Flow Rate (Qmax) (milliliters per second (mL/sec)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [milliliters per second (mL/sec)]	9.6 (2.50)	10.4 (2.78)	10.0 (2.65)
Postvoid Residual Volume (milliliters (mL)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [milliliters (mL)]	59.0 (59.11)	47.8 (44.47)	53.6 (52.56)
Prostate Specific Antigen (nanograms per milliliter (ng/mL)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [nanograms per milliliter (ng/mL)]	1.9 (1.70)	2.1 (1.93)	2.0 (1.81)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to 8-Week Endpoint in Arterial Resistive Index (RI) in the Prostate Transition Zone
Description	Arterial RI was a measure of vascular resistance using Doppler ultrasound. RI was the ratio of (peak systolic velocity - end diastolic velocity)/peak systolic velocity, and increased as resistance to blood flow increased. The least squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included fixed effects for treatment, region, visit, and treatment-by-visit interaction, baseline as a covariate, a random effect of participant within treatment, and an unstructured covariance matrix.
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of study medication, had non-missing data (arterial RI in the prostate transition zone) at baseline, and a post-baseline visit.

Arm/Group Title	Placebo	Tadalafil
Arm/Group Description	Placebo: tablet administered orally, once daily for 8 weeks.	Tadalafil: 5-milligram (mg) tablet administered orally, once daily for 8 weeks.
Measure Participants	43	38
Least Squares Mean (Standard Error) [ratio]	-0.01 (0.006)	0.00 (0.006)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tadalafil
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.121
	Comments	The p-value associated with the LS mean difference of change from baseline to Week 8 between the tadalafil and placebo treatment groups was tested at a significance level of 0.05 with no adjustments for multiplicity.
	Method	Mixed-Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	0.01
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.009
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline to 4-Week Endpoint in Arterial Resistive Index (RI) in the Prostate Transition Zone
Description	Arterial RI was a measure of vascular resistance using Doppler ultrasound. RI was the ratio of (peak systolic velocity - end diastolic velocity)/peak systolic velocity, and increased as resistance to flow increased. The least squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included fixed effects for treatment, region, visit, and treatment-by-visit interaction, baseline as a covariate, a random effect of participant within treatment, and an unstructured covariance matrix.
Time Frame	Baseline, Week 4

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of study medication, had non-missing data (arterial RI in the prostate transition zone) at baseline, and a post-baseline visit.

Arm/Group Title	Placebo	Tadalafil
Arm/Group Description	Placebo: tablet administered orally, once daily for 8 weeks.	Tadalafil: 5-milligram (mg) tablet administered orally, once daily for 8 weeks.
Measure Participants	45	43
Least Squares Mean (Standard Error) [ratio]	0.00 (0.006)	0.01 (0.006)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tadalafil
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.226
	Comments	The p-value associated with the LS mean difference of change from baseline to Week 4 between the tadalafil and placebo treatment groups was tested at a significance level of 0.05 with no adjustments for multiplicity.
	Method	Mixed-Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	0.01
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.008
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline to 4 and 8 Weeks in Arterial Resistive Index (RI) in the Prostate Peripheral Zone and Bladder Neck
Description	Arterial RI was a measure of vascular resistance using Doppler ultrasound. RI was the ratio of (peak systolic velocity - end diastolic velocity)/peak systolic velocity, and increased as resistance to flow increased. The least squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included fixed effects for treatment, region, visit, and treatment-by-visit interaction, baseline as a covariate, a random effect of participant within treatment, and an unstructured covariance matrix.
Time Frame	Baseline, Week 4 and Week 8

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of study medication.

Arm/Group Title	Placebo	Tadalafil
Arm/Group Description	Placebo: tablet administered orally, once daily for 8 weeks.	Tadalafil: 5-milligram (mg) tablet administered orally, once daily for 8 weeks.
Measure Participants	45	43
Week 4 Change, Prostate Peripheral Zone (n=45, 43)	0.00 (0.006)	0.01 (0.007)
Week 8 Change, Prostate Peripheral Zone (n=43, 38)	-0.01 (0.006)	0.01 (0.007)
Week 4 Change, Bladder Neck (n=30, 30)	-0.01 (0.012)	0.01 (0.012)
Week 8 Change, Bladder Neck (n=32, 26)	0.01 (0.015)	0.02 (0.016)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tadalafil
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.208
	Comments	The p-value associated with the LS mean difference of change from baseline to Week 4 in the prostate peripheral zone RI was tested at a significance level of 0.05 with no adjustments for multiplicity.
	Method	Mixed-Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	0.01
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.009
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tadalafil
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.066
	Comments	The p-value associated with the LS mean difference of change from baseline to Week 8 in the prostate peripheral zone RI was tested at a significance level of 0.05 with no adjustments for multiplicity.
	Method	Mixed-Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	0.02
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.009
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tadalafil
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.195
	Comments	The p-value associated with the LS mean difference of change from baseline to Week 4 in bladder neck RI was tested at a significance level of 0.05 with no adjustments for multiplicity.
	Method	Mixed-Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	0.02
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.017
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tadalafil
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.625
	Comments	The p-value associated with the LS mean difference of change from baseline to Week 8 in bladder neck RI was tested at a significance level of 0.05 with no adjustments for multiplicity.
	Method	Mixed-Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	0.01
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.022
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline to 4 and 8 Weeks in Color Pixel Intensity (CPI) in the Prostate Transition Zone, Peripheral Zone, and Bladder Neck
Description	CPI quantified blood flow in a pre-specified region of interest by using color Doppler imaging. CPI was the mean color pixel intensity in the region of interest and scores could range from 0 to 160. An increase in CPI reflected an increase in blood flow. The least squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included fixed effects for treatment, region, visit, and treatment-by-visit interaction, baseline as a covariate, a random effect of participant within treatment, and an unstructured covariance matrix.
Time Frame	Baseline, Week 4 and Week 8

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of study medication.

Arm/Group Title	Placebo	Tadalafil
Arm/Group Description	Placebo: tablet administered orally, once daily for 8 weeks.	Tadalafil: 5-milligram (mg) tablet administered orally, once daily for 8 weeks.
Measure Participants	44	43
Week 4 Change, Prostate Transition Zone (n=44, 43)	-2.21 (2.377)	0.42 (2.408)
Week 8 Change, Prostate Transition Zone (n=43, 38)	2.02 (1.974)	2.53 (2.083)
Week 4 Change, Prostate Peripheral Zone (n=44, 43)	-1.48 (2.059)	1.99 (2.091)
Week 8 Change, Prostate Peripheral Zone (n=43, 38)	3.11 (1.868)	2.55 (1.987)
Week 4 Change, Bladder Neck (n=42, 40)	7.37 (4.022)	3.17 (4.140)
Week 8 Change, Bladder Neck (n=38, 36)	-0.13 (3.622)	7.81 (3.738)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tadalafil
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.439
	Comments	The p-value associated with the LS mean difference of change from baseline to Week 4 in the prostate transition zone CPI was tested at a significance level of 0.05 with no adjustments for multiplicity.
	Method	Mixed-Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	2.63
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.380
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tadalafil
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.860
	Comments	The p-value associated with the LS mean difference of change from baseline to Week 8 in the prostate transition zone CPI was tested at a significance level of 0.05 with no adjustments for multiplicity.
	Method	Mixed-Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	0.51
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.867
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tadalafil
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.240
	Comments	The p-value associated with the LS mean difference of change from baseline to Week 4 in the prostate peripheral zone CPI was tested at a significance level of 0.05 with no adjustments for multiplicity.
	Method	Mixed-Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	3.47
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.937
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tadalafil
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.839
	Comments	The p-value associated with the LS mean difference of change from baseline to Week 8 in the prostate peripheral zone CPI was tested at a significance level of 0.05 with no adjustments for multiplicity.
	Method	Mixed-Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	-0.55
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.729
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tadalafil
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.468
	Comments	The p-value associated with the LS mean difference of change from baseline to Week 4 in the bladder neck CPI was tested at a significance level of 0.05 with no adjustments for multiplicity.
	Method	Mixed-Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	-4.20
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.770
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tadalafil
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.131
	Comments	The p-value associated with the LS mean difference of change from baseline to Week 8 in the bladder neck CPI was tested at a significance level of 0.05 with no adjustments for multiplicity.
	Method	Mixed-Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	7.93
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.199
	Estimation Comments

Adverse Events

Arm/Group Title	Placebo		Tadalafil
Arm/Group Description	Placebo: tablet administered orally, once daily for 8 weeks.		Tadalafil: 5-milligram (mg) tablet administered orally, once daily for 8 weeks.
All Cause Mortality
	Placebo		Tadalafil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Tadalafil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/50 (4%)		0/47 (0%)
Cardiac disorders
Cardiac arrest	1/50 (2%)	1	0/47 (0%)	0
Myocardial infarction	1/50 (2%)	1	0/47 (0%)	0
Nervous system disorders
Carotid artery stenosis	1/50 (2%)	1	0/47 (0%)	0
Ischaemic cerebral infarction	1/50 (2%)	1	0/47 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Tadalafil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/50 (8%)		10/47 (21.3%)
Gastrointestinal disorders
Abdominal pain upper	0/50 (0%)	0	1/47 (2.1%)	1
Dyspepsia	0/50 (0%)	0	1/47 (2.1%)	1
Gastric disorder	0/50 (0%)	0	1/47 (2.1%)	1
Gastrooesophageal reflux disease	1/50 (2%)	1	0/47 (0%)	0
Infections and infestations
Bronchitis	0/50 (0%)	0	1/47 (2.1%)	1
Nasopharyngitis	0/50 (0%)	0	1/47 (2.1%)	1
Subcutaneous abscess	1/50 (2%)	1	0/47 (0%)	0
Injury, poisoning and procedural complications
Fall	0/50 (0%)	0	1/47 (2.1%)	1
Rib fracture	0/50 (0%)	0	1/47 (2.1%)	1
Metabolism and nutrition disorders
Hypercholesterolaemia	1/50 (2%)	1	0/47 (0%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain	0/50 (0%)	0	1/47 (2.1%)	1
Nervous system disorders
Headache	1/50 (2%)	1	4/47 (8.5%)	4
Hypoaesthesia	1/50 (2%)	1	0/47 (0%)	0
Psychiatric disorders
Depression	1/50 (2%)	1	0/47 (0%)	0
Renal and urinary disorders
Nephrolithiasis	0/50 (0%)	0	1/47 (2.1%)	1
Pollakiuria	0/50 (0%)	0	1/47 (2.1%)	1
Renal colic	0/50 (0%)	0	1/47 (2.1%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/50 (2%)	1	0/47 (0%)	0
Wheezing	1/50 (2%)	1	0/47 (0%)	0

Limitations/Caveats

The primary and secondary efficacy analyses of resistive index (RI) and color pixel intensity (CPI) were based on centrally-read data.

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.