Multinational Study to Evaluate Tadalafil in Asian Men With Signs and Symptoms of Benign Prostatic Hyperplasia

Study Overview
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Brief Summary
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This study is a randomized, double-blind, placebo and tamsulosin-controlled, parallel design, multinational study to evaluate the efficacy and safety of Tadalafil once-a-day dosing for 12 weeks in Asian men with signs and symptoms of benign prostatic hyperplasia (BPH).

Official Title
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A Phase 3, Randomized, Double Blind, Placebo and Tamsulosin Controlled, Parallel Design, Multinational Study to Evaluate the Efficacy and Safety of Tadalafil Once a Day Dosing for 12 Weeks in Asian 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
* Drug: Tamsulosin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Asian males, with benign prostatic hyperplasia (BPH) for at least 6 months prior to initiation and IPSS score greater than or equal to 13 at the beginning of the treatment Agree not to use any other approved or experimental pharmacologic BPH, erectile dysfunction (ED) and overactive bladder (OAB) treatments at any time during the study. Have not taken Finasteride or Dutasteride therapy, Anti-androgenic hormone or any other BPH therapy, ED or OAB therapy for specified duration of time prior to the beginning of the treatment Exclusion Criteria: Prostate specific antigen (PSA) score beyond acceptable range defined for study at initiation History of urinary retention or lower urinary tract (bladder) stones within 6 months of initiation History of urinary urethral obstruction due to stricture, valves, sclerosis, or tumor at initiation Clinical evidence of prostate cancer at initiation Clinical evidence of any of the bladder or urinary tract conditions, which may affect lower urinary tract symptom at initiation History of cardiac conditions, including Angina requiring certain treatment with nitrates, unstable angina defined for study, positive cardiac stress test before starting the study History of significant central nervous system injuries (including stroke or spinal cord injury within 6 months of initiation) Use of any nitrates, cancer chemotherapy, androgens, antiandrogens, estrogens, luteinizing hormone-releasing hormone (LHRH)agonists/antagonists, or anabolic steroids at initiation

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* PO, QD (30 min after meal) for 12 weeks<br>|
| Experimental: 2.5 mg Tadalafil<br> | Drug: Tadalafil<br>* by mouth (PO), once daily (QD) (30 min after meal) for 12 weeks<br>* Other names: LY450190, Cialis;|
| Experimental: 5.0 mg Tadalafil<br> | Drug: Tadalafil<br>* by mouth (PO), once daily (QD) (30 min after meal) for 12 weeks<br>* Other names: LY450190, Cialis;|
| Active Comparator: 0.2 mg Tamsulosin<br> | Drug: Tamsulosin<br>* PO, QD (30 min after meal) 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 International Prostate Symptom Score (IPSS) at 12 Weeks | The IPSS Total Score is obtained by combining the scores of the responses to 1 through 7 component questions. Each question is scored from 0-5 for an IPSS range of 0-35 points; higher numerical scores from the IPSS questionnaire represent greater severity of symptoms. Least Squares Mean values were controlled for prior alpha blocker use (yes/no), country (Japan/Korea/Taiwan) and baseline value. | baseline, 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 12 Weeks in International Prostate Symptom Score (IPSS) Subscore (Storage [Irritative] and Voiding [Obstructive]) | 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); 4 questions of the obstructive score range from 0 to 20. IPSS irritative subscore is the sum of Questions 2, 4 and 7 of IPSS questionnaire. Scores range from 0 (no irritative symptoms) to 5 (frequent irritative symptoms); 3 questions of the irritative subscore range from 0 to 15. Least Squares Mean values were controlled for prior alpha blocker use (yes/no), country (Japan/Korea/Taiwan), and baseline value. | baseline, 12 weeks | 
| Change From Baseline in International Prostate Symptom Score (IPSS) Quality of Life (QoL) at 12 Weeks | Assessment of QoL by urinary symptoms, with scores ranging from 0 (delighted) to 6 (terrible). Least Squares Mean values were controlled for Benign Prostatic Hyperplasia severity (moderate/severe), prior alpha blocker use (yes/no), country (Japan/Korea/Taiwan), and baseline value. | baseline, 12 weeks | 
| Change From Baseline in Benign Prostatic Hyperplasia (PBH) Impact Index (BII) at 12 Weeks | 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. Least Squares Mean values were controlled for BPH severity (moderate/severe), prior alpha blocker use (yes/no), country (Japan/Korea/Taiwan) and baseline value. | baseline, 12 weeks | 
| Change From Baseline in Uroflowmetry Parameter: Peak Flow Rate (Qmax) at 12 Weeks | Qmax: defined as the peak urine flow rate (measured in milliliters per second [mL/second] using standard calibrated flowmeter). Least Squares Mean values were controlled for Benign Prostatic Hyperplasia (BPH) severity (moderate/severe), prior alpha blocker use (yes/no), country (Japan/Korea/Taiwan), and baseline value. | baseline, 12 weeks | 
| Patient Global Impression of Improvement (PGI-I) at Week 12 | The PGI-I measures the patient's perception of improvement at the time of assessment compared with the start of treatment. There are 7 categories with scores ranging from 1 (very much better) to 7 (very much worse). The data are presented as the number of participants in each of the 7 categories: very much better (1); much better (2); a little better (3); no change (4); a little worse (5); much worse (6); very much worse (7). | 12 weeks | 
| Clinician Global Impression of Improvement (CGI-I) at Week 12 | The CGI-I measures clinician's perception of patient improvement at the time of assessment compared with the start of treatment. There are 7 categories with scores ranging from 1 (very much better) to 7 (very much worse). The data are presented as the number of participants in each of the 7 categories: very much better (1); much better (2); a little better (3); no change (4); a little worse (5); much worse (6); very much worse (7). | 12 weeks | 
| Change From Baseline in Prostate Specific Antigen (PSA) at 12 Weeks | Nanograms of PSA per milliliter (ng/mL) of blood. | baseline, 12 weeks | 
| Change From Baseline in Postvoid Residual Volume (PVR) at 12 Weeks | The PVR is defined as the volume of urine remaining in the bladder after voiding, estimated by ultrasound. | baseline, 12 weeks | 
| Change From Baseline in Blood Pressure (Sitting) at 12 Weeks |  | baseline, 12 weeks | 
| Change From Baseline in Blood Pressure (Standing) at 12 Weeks |  | baseline, 12 weeks | 
| Change From Baseline in Sitting Heart Rate (HR) at 12 Weeks |  | baseline, 12 weeks |