A Study of Tadalafil in Men With Benign Prostatic Hyperplasia

Study Overview
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Brief Summary
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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.)

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Global Multicenter Study to Evaluate the Efficacy and Safety of Tadalafil Once Daily Dosing for 12 Weeks in Men With Signs and Symptoms of Benign Prostatic Hyperplasia

Conditions
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Benign Prostatic Hyperplasia (BPH)

Intervention / Treatment
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* Drug: Tadalafil 5 mg
* Drug: Placebo tablet
* Drug: Tamsulosin
* Drug: Placebo capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men 45 years of age or older with benign prostatic hyperplasia (BPH) also referred to as BPH-lower urinary tract symptoms (LUTS) on the disease diagnostic criteria at the start of study. Provide signed informed consent at the start of the study. Agree not to use any other approved or experimental pharmacologic BPH, overactive bladder (OAB), or erectile dysfunction (ED) treatments anytime during 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), OAB therapy, ED therapy for at least 4 weeks prior to study drug is dispensed. Have LUTS with a total International Prostate Symptom Score (IPSS) greater than or equal to 13 when study drug is dispensed. Have reduced urine flow (measured by special toilet equipment). Demonstrate compliance with study drug administration requirements. Exclusion Criteria: Treated with nitrates 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 certain neurological conditions associated with bladder problems or injuries to brain or spinal cord within a specified time of starting this study. Have uncontrolled diabetes. Have prostate cancer, are being treated for cancer. Have prostate specific antigen (PSA) greater than 10 nanograms per milliliter (ng/mL) at the start of study.

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo tablet with tamsulosin dose orally (po) once daily (QD) and placebo capsule with tadalafil dose po QD for 12 weeks | Drug: Placebo tablet<br>* Placebo tablet po QD for 12 weeks<br>Drug: Placebo capsule<br>* Placebo capsule po QD for 12 weeks<br>|
| Experimental: Tadalafil 5 milligram (mg)<br>Tadalafil 5 mg tablet po QD and placebo capsule po QD for 12 weeks | Drug: Tadalafil 5 mg<br>* Tadalafil 5 mg po QD for 12 weeks<br>* Other names: LY450190;|
| Active Comparator: Tamsulosin 0.4 mg<br>Tamsulosin 0.4 mg capsule po QD and placebo tablet po QD for 12 weeks | Drug: Tamsulosin<br>* Tamsulosin 0.4 mg po QD for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total International Prostate Symptom Score (IPSS) at 12 Weeks | The IPSS Total Score was obtained by combining the scores of the responses to Component Questions 1-7. Each question was scored from 0-5 for an IPSS range of 0-35 points; higher numerical scores from the IPSS questionnaire represented greater severity of symptoms. Least Squares (LS) Mean of change from baseline to endpoint (Week 12 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction. | Baseline, 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total International Prostate Symptom Score (IPSS) at 4 Weeks | The IPSS Total Score was obtained by combining the scores of the responses to Component Questions 1-7. Each question was scored from 0-5 for an IPSS range of 0-35 points; higher numerical scores from the IPSS questionnaire represented greater severity of symptoms. Least Squares (LS) Mean of change from baseline to endpoint (Week 4 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction. | Baseline, 4 weeks | 
| Change From Baseline in International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore at 12 Weeks | IPSS storage (irritative) subscore was the sum of Component Questions 2, 4 and 7 of the IPSS questionnaire. Scores ranged from 0 (no irritative symptoms) to 5 (frequent irritative symptoms); therefore, the 3 questions of the irritative subscore ranged from 0 to 15. Least Squares (LS) Mean of change from baseline to endpoint (Week 12 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction. | Baseline, 12 weeks | 
| Change From Baseline in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore at 12 Weeks. | IPSS voiding (obstructive) subscore was the sum of Component Questions 1, 3, 5 and 6 of the IPSS questionnaire. Scores ranged from 0 (no obstructive symptoms)-5 (frequent obstructive symptoms); therefore, the 4 questions of the obstructive score ranged from 0-20. Least Squares (LS) Mean of change from baseline to endpoint (Week 12 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction. | Baseline, 12 weeks | 
| Change From Baseline in International Prostate Symptom Score (IPSS) Nocturia Question at 12 Weeks | The IPSS nocturia question (Component Question 7) measured nocturia (need to urinate at night) over the past 4 weeks. Scores ranged from 0 (no episodes of nocturia)-5 (5 or more episodes of nocturia). Least Squares (LS) Mean of change from baseline to endpoint (Week 12 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction. | Baseline, 12 weeks | 
| Change From Baseline in International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index at 12 Weeks | IPSS QoL assessed QoL by urinary symptoms, with scores ranging from 0 (delighted)-6 (terrible). Least Squares (LS) Mean of change from baseline to endpoint (Week 12 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction. | Baseline, 12 weeks | 
| Change From Baseline in Modified International Prostate Symptom Score (mIPSS) at 1 Week | The mIPSS Total Score covered a time period of 1 week and was obtained by combining scores of responses to Component Questions 1-7. Each question was scored from 0-5 for an mIPSS range of 0-35 points; higher numerical scores represented greater severity of symptoms. Least Squares (LS) Mean of change from baseline to endpoint (Week 1 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction. | Baseline, 1 week | 
| Change From Baseline in Benign Prostatic Hyperplasia Impact Index (BII) at 4 Weeks | BII was a 4-item, self-administered questionnaire evaluating impact of urinary problems on overall health and activity. Total scores ranged from 0-13; higher scores represented increased perceived impact of BPH-lower urinary tract symptoms (LUTS) on overall health. Least Squares (LS) Mean of change from baseline to endpoint (Week 4 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction. | Baseline, 4 weeks | 
| Change From Baseline in Benign Prostatic Hyperplasia Impact Index (BII) at 12 Weeks | BII was a 4-item, self-administered questionnaire evaluating impact of urinary problems on overall health and activity. Total scores ranged from 0-13; higher scores represented increased perceived impact of BPH-lower urinary tract symptoms (LUTS) on overall health. Least Squares (LS) Mean of change from baseline to endpoint (Week 12 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction. | Baseline, 12 weeks | 
| Patient Global Impression of Improvement (PGI-I) at 12 Weeks | The PGI-I was a participant-rated instrument that measured the improvement or worsening of the participant's symptoms based on a 7-point scale at Week 12. A score of 1=participant felt symptoms were very much better; score of 2=participant felt symptoms were much better; score of 3=participant felt symptoms were a little better; score of 4=participant felt no change in symptoms; score of 5=participant felt symptoms were a little worse; score of 6=participant felt symptoms were much worse; score of 7=participant felt symptoms were very much worse. | 12 weeks | 
| Clinician Global Impression of Improvement (CGI-I) at 12 Weeks | The CGI-I was an investigator-rated instrument that measured improvement or worsening of the participant's symptoms based on a 7-point scale. A score of 1=participant felt symptoms were very much better; score of 2=participant felt symptoms were much better; score of 3=participant felt symptoms were a little better; score of 4=participant felt no change in symptoms; score of 5=participant felt symptoms were a little worse; score of 6=participant felt symptoms were much worse; score of 7=participant felt symptoms were very much worse. | 12 weeks | 
| Treatment Satisfaction Scale - Benign Prostatic Hyperplasia (TSS-BPH) at 12 Weeks: Overall | The TSS-BPH was a validated participant-rated instrument that measured participant satisfaction with treatment based on a 13-item questionnaire. The overall TSS-BPH score was converted to a percentage of the maximum value possible (percent ranged from 0-100) with lower scores indicating greater satisfaction. | 12 weeks | 
| Change From Baseline in International Index of Erectile Function (IIEF) Erectile Function (EF) Domain at 12 Weeks | IIEF measured self-reported EF over the past 4 weeks. Scores ranged from 0 (low or no EF)-5 (high EF) on 6 questions (1-5, 15 of the IIEF). Total EF Domain scores ranged from 1-30. Least Squares (LS) Mean of change from baseline to endpoint (Week 12 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction. | Baseline, 12 weeks | 
| Change From Baseline in Peak Urine Flow Rate (Q-Max) at 12 Weeks | Q-max (peak urine flow rate) was measured in milliliters per second (mL/sec) using a standard calibrated flowmeter. At each visit, a uroflowmetry assessment was considered valid and data were included in the analyses only if the prevoid total bladder volume (assessed by ultrasound) was ≥150 to ≤550 mL and the voided volume (V-comp) was ≥125 mL. | Baseline, 12 weeks | 
| Change From Baseline in Mean Urine Flow Rate (Q-Mean) at 12 Weeks | Q-mean (mean urine flow rate) was measured in milliliters per second (mL/sec) using a standard calibrated flowmeter. At each visit, a uroflowmetry assessment was considered valid and data were included in the analyses only if the prevoid total bladder volume (assessed by ultrasound) was ≥150 to ≤550 mL and the voided volume (V-comp) was >=125 mL. | Baseline, 12 weeks | 
| Change From Baseline in Volume of Voided Urine (V-Comp) at 12 Weeks | V-comp (volume of urine voided) was measured in milliliters (mL) using a standard calibrated flowmeter. At each visit, a uroflowmetry assessment was considered valid and data were included in the analyses only if the prevoid total bladder volume (assessed by ultrasound) was ≥150 to ≤550 mL and V-comp was ≥125 mL. | Baseline, 12 weeks | 
| Change From Baseline in Postvoid Residual Volume (PVR) at 12 Weeks | PVR was the amount of urine remaining in the bladder after void completion. | Baseline, 12 weeks |