A Study in Benign Prostatic Hyperplasia

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Benign Prostatic Hyperplasia

Intervention / Treatment
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* Drug: Tadalafil
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5 milligrams (mg) Tadalafil<br> | Drug: Tadalafil<br>* Administered orally, once daily for 8 weeks<br>* Other names: LY450190;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Administered orally, once daily for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 8-Week Endpoint in Arterial Resistive Index (RI) in the Prostate Transition Zone | 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. | Baseline, Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 4-Week Endpoint in Arterial Resistive Index (RI) in the Prostate Transition Zone | 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. | Baseline, Week 4 | 
| Change From Baseline to 4 and 8 Weeks in Arterial Resistive Index (RI) in the Prostate Peripheral Zone and Bladder Neck | 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. | Baseline, Week 4 and Week 8 | 
| Change From Baseline to 4 and 8 Weeks in Color Pixel Intensity (CPI) in the Prostate Transition Zone, Peripheral Zone, and Bladder Neck | 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. | Baseline, Week 4 and Week 8 |