Study of Tadalafil Once-a Day for 12 Weeks in Men With Signs and Symptoms of Benign Prostatic Hyperplasia

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, parallel-design, multinational, 12-week study to compare the efficacy, dose response, and safety of tadalafil once a day versus placebo in men with signs and symptoms of benign prostatic hyperplasia, including lower urinary tract symptoms.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, 5-Group, Multinational Study to Evaluate the Efficacy, Dose Response, and Safety of Tadalafil Once-a-Day Dosing 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: tadalafil
* Drug: tadalafil
* Drug: tadalafil
* Drug: tadalafil
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males, 45 years or older, with benign prostatic hyperplasia, including lower urinary tract symptoms for at least 6 months prior to Visit 1 and an International Prostate Symptom Score (IPSS) greater than or equal to 13 at Visit 2. Agree not to use approved or experimental benign prostatic hyperplasia or erectile dysfunction treatments anytime during the study Have not taken finasteride or dutasteride therapy, any other lower urinary tract symptom (LUTS) therapy or phosphodiesterase type 5 (PDE5) inhibitors for specified duration of time prior to Visit 2. Have a prostate specific antigen (PSA) score within acceptable range defined for study or negative biopsy of the prostate for cancer within 12 months of Visit 1. Exclusion Criteria: History of urinary retention or lower urinary tract (bladder) stones 6 months before the start of the study History of bladder outlet obstruction or urethral obstruction due to stricture, valves, sclerosis, or tumor. History of cardiac conditions including angina requiring certain treatment with nitrates, heart disease or coronary conditions including myocardial infarction, bypass surgery, angioplasty or stent placement for a specified time before starting the study. Certain neurological conditions associated with bladder problems or injuries to the brain or spinal cord within a specified time before starting the study. Nitrate use

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 |
| --- | --- |
| Placebo Comparator: 1<br>placebo tablet | Drug: placebo<br>* Placebo tablet taken by mouth one a day for twelve weeks<br>|
| Active Comparator: 2<br>2.5 mg tadalafil tablet | Drug: tadalafil<br>* 2.5 mg tadalafil tablet by mouth once a day for twelve weeks.<br>* Other names: IC351;|
| Active Comparator: 3<br>5 mg tadalafil tablet | Drug: tadalafil<br>* 5 mg tadalafil tablet by mouth once a day for twelve weeks.<br>* Other names: IC351;|
| Active Comparator: 4<br>10 mg tadalafil tablet | Drug: tadalafil<br>* 10 mg tadalafil tablet by mouth once a day for twelve weeks.<br>* Other names: IC351;|
| Active Comparator: 5<br>20 mg tadalafil tablet | Drug: tadalafil<br>* 20 mg tadalafil tablet by mouth once a day for twelve weeks.<br>* Other names: IC351;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS): Primary Analysis | Assesses the severity of BPH-LUTS and the response to therapy. The total score was derived by summing the scores of the responses to the 7 component questions. Scores range from 0 to 35; 0-7 Mildly symptomatic; 8-19 moderately symptomatic; 20-35 severely symptomatic. | Baseline and 12 weeks | 
| Change From Baseline to Week 12 in International Prostate Symptom Score (IPSS): Supportive Analysis | Assesses the severity of BPH-LUTS and the response to therapy. The total score was derived by summing the scores of the responses to the 7 component questions. Scores range from 0 to 35; 0-7 Mildly symptomatic; 8-19 moderately symptomatic; 20-35 severely symptomatic. | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) (Irritative) Subscore | Measures irritative symptoms over the past 4 weeks of the IPSS. IPSS irritative subscore is the sum of Questions 2, 4 and 7 of the IPSS questionnaire. Scores range from 1 (few irritative symptoms) to 5 (frequent irritative symptoms), thus the 3 questions of the irritative subscore range from 0 to 15. | baseline and 12 weeks | 
| Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore | Measures obstructive symptoms over the past 4 weeks of the IPSS. IPSS obstructive subscore is the sum of Questions 1, 3, 5 and 6 of the IPSS questionnaire. Scores range from 1 (few obstructive symptoms) to 5 (frequent obstructive symptoms), thus the 4 questions of the obstructive score range from 0 to 20. | 12 weeks | 
| Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Question 7 (Nocturia) | Measures nocturia (the need to get up at night to urinate) over the past 4 weeks. Scores range from 1 (few episodes of nocturia) to 5 (frequent episodes of nocturia). | baseline and 12 weeks | 
| Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index | Assessment of quality of life (QOL) by urinary symptoms, with scores ranging from 0 (delighted) to 6 (terrible). | baseline and 12 weeks | 
| Change From Baseline to 12 Week Endpoint in Benign Prostatic Hyperplasia Impact Index (BII) | Measures the impact that symptoms of BPH has on the patients well being. This questionnaire has 4 questions assessing the level of urinary discomfort and it's impact on the patients. Three questions range from 0 (no impact) to 4 (high impact); one question ranges from 0 (low impact) to 4 (high impact). The BII score ranges from 0 to 16. | baseline and 12 weeks | 
| Number of Participants Who Answer Yes to the Lower Urinary Tract Symptoms (LUTS) Global Assessment Question (LUTS-GAQ) | LUTS-GAQ Question asks the participant if the treatment they have been on has improved their uninary symptoms. | 12 weeks | 
| Change From Baseline to 12 Week Endpoint in Peak Urinary Flow | Measures the maximum flow rate of urine (measured in mL/s). This is a continuous parameter with positive numeric values. | baseline and 12 weeks | 
| Change From Baseline to 12 Week Endpoint in International Index of Erectile Function (IIEF) EF Domain | Measures erectile function over the past 4 weeks on Questions 1-5 and 15 (6 questions) of the International Index of Erecile Function (IIEF) questionnaire. Scores range from 0 (low/no erectile function) to 5 (high erectile function), thus the 6 questions of the IIEF-EF domain range from 0 to 30. | baseline and 12 weeks |