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

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, Multinational Study to Evaluate the Efficacy and Safety of Daily Tadalafil for 12 Weeks 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: Placebo
* Drug: tadalafil


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-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).

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tadalafil<br> | Drug: tadalafil<br>* Following a 4-week placebo lead-in period, subjects received tadalafil 5 mg tablet by mouth once daily over a 12-week period.<br>* Other names: LY450190;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Following a 4-week placebo lead-in period, subjects received placebo tablet by mouth once daily over a 12-week period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) | 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. | Baseline, 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 4 Weeks, Benign Prostatic Hyperplasia (BPH) Impact Index | 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. | Baseline, 4 weeks | 
| Change From Baseline to 12 Weeks, Benign Prostatic Hyperplasia (BPH) Impact Index | 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. | Baseline, 12 weeks | 
| Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore | 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. | Baseline, 12 weeks | 
| Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore | 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. | Baseline, 12 weeks | 
| Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Nocturia Question | 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. | Baseline, 12 weeks | 
| Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index | 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. | Baseline, 12 weeks | 
| Patient Global Impression of Improvement (PGI-I), Number of Participants in 7 Response Categories | 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). | 12 weeks | 
| Clinical Global Impression of Improvement (CGI-I), Number of Participants in 7 Response Categories | 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). | 12 weeks | 
| Change From Baseline to 1 Week, International Prostate Symptom Score (IPSS) | 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. | Baseline, 1 week | 
| Change From Baseline to 4 Weeks, International Prostate Symptom Score (IPSS) | 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. | Baseline, 4 Weeks | 
| Change From Baseline to 12 Weeks, International Index of Erectile Function (IIEF)- Erectile Function (EF) Domain Scores | 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. | Baseline, 12 weeks | 
| Change From Baseline to 12 Weeks, Peak Flow Rate (Qmax) by Uroflowmetry | 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. | Baseline, 12 weeks | 
| Change From Baseline to 12 Weeks, Mean Flow Rate (Qmean) by Uroflowmetry | 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. | Baseline, 12 weeks | 
| Change From Baseline to 12 Weeks, Voided Volume (Vcomp) by Uroflowmetry | 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. | Baseline, 12 weeks | 
| Change From Baseline to 12 Weeks, Postvoid Residual (PVR) Volume | The amount of urine remaining in the bladder after void completion. | Baseline, 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Signs and Symptoms, Prostatic Hyperplasia, Hyperplasia, Genital Diseases, Male, Prostatic Diseases, BPH-LUTS