Study of Tadalafil Once-a-Day for 12 Weeks in Japanese Men With Benign Prostatic Hyperplasia Followed by an Open-Label Extension

Study Overview
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Brief Summary
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This study is a randomized, double-blind, placebo-controlled, parallel-design to compare the efficacy and safety of tadalafil once-a-day dosing versus placebo for 12 weeks followed by an open-label extension to evaluate the long-term safety and efficacy of tadalafil in Japanese men with signs and symptoms of benign prostatic hyperplasia.

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Design Study to Evaluate the Efficacy and Safety of Tadalafil Once-a-Day Dosing for 12 Weeks Followed by an Open-Label Extension to Evaluate the Long-Term Safety and Efficacy of Tadalafil in Japanese 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 2.5 mg
* Drug: Tadalafil 5 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Japanese Males, 45 years old or older, with benign prostatic hyperplasia (BPH) 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 any other approved or experimental pharmacologic BPH, erectile dysfunction (ED), and/or 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 Visit 2. Exclusion Criteria: Prostate specific antigen (PSA) score beyond acceptable range defined for study at Visit 1. History of urinary retention or lower urinary tract (bladder) stones within 6 months of Visit 1. History of urethral obstruction due to stricture, valves, sclerosis, or tumor at Visit 1. Clinical evidence of prostate cancer at Visit 1. Clinical evidence of any of the bladder or urinary tract conditions, which may affect lower urinary tract symptom at Visit 1. 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 (CNS) injuries (including stroke or spinal cord injury) within 6 months of Visit 1. Use of any nitrates, cancer chemotherapy, androgens, antiandrogens, estrogens, luteinizing hormone-releasing hormone (LHRH) agonists/antagonists, or anabolic steroids at Visit 1.

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 |
| --- | --- |
| Experimental: Tadalafil 2.5 milligrams (mg)<br>2.5 mg tadalafil tablet by mouth once a day for 12 weeks followed by 5 mg tadalafil tablet by mouth once a day for 42 weeks. | Drug: Tadalafil 2.5 mg<br>* oral, daily<br>* Other names: Cialis;|
| Experimental: Tadalafil 5 mg<br>5 mg tadalafil tablet by mouth once a day for 12 weeks then continue 5 mg tadalafil tablet by mouth once a day for 42 weeks. | Drug: Tadalafil 5 mg<br>* oral, daily<br>* Other names: Cialis;|
| Placebo Comparator: Placebo<br>Placebo tablet taken by mouth once a day for 12 weeks. Then subjects may take 5 mg tadalafil tablet by mouth once a day for 42 weeks. | Drug: Placebo<br>* oral, daily<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) Total Score at 12-Week Endpoint | 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. | Baseline, 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore at 12-Week Endpoint | IPSS storage (irritative) subscore is the sum of Questions 2, 4 and 7 of the IPSS questionnaire. Scores range from 0 (not at all) to 5 (frequent irritative symptoms), thus the 3 questions of the irritative subscore range from 0 to 15. | Baseline, 12 weeks | 
| Change From Baseline in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore at 12-Week Endpoint | IPSS obstructive subscore is the sum of Questions 1, 3, 5 and 6 of the IPSS questionnaire. Scores range from 0 (not at all) to 5 (frequent obstructive symptoms), thus the 4 questions of the obstructive score range from 0 to 20. | Baseline, 12 weeks | 
| Change From Baseline in IPSS Quality of Life (QoL) Index at 12-Week Endpoint | Assessment of quality of life (QOL) by urinary symptoms, with scores ranging from 0 (delighted) to 6 (terrible). | Baseline, 12 weeks | 
| Change From Baseline in Overactive Bladder Symptom Score (OABSS) at 12-Week Endpoint | The OABSS is a four-symptom questionnaire to assess overactive bladder (OAB) symptoms: daytime frequency, nighttime frequency, urgency, and urgency incontinence. Scores range from 0 - 15, with higher scores indicating more severe OAB symptoms. | Baseline, 12 weeks | 
| Change From Baseline in Uroflowmetry Parameter: Peak Flow Rate (Qmax) at 12-Week Endpoint | Uroflowmetry was assessed by Qmax, defined as the peak urine flow rate (measured in mL/second using a standard calibrated flowmeter). | Baseline, 12 weeks | 
| Tadalafil Pharmacokinetics in Japanese Men: Plasma Concentration Measurement | Plasma from participants in the tadalafil treatment groups were assayed using a validated liquid chromatographic/mass spectrometric (LC/MS) method. | Baseline, 12 weeks | 
| Number of Participants With Adverse Events During 12 Weeks of the Study | A listing of Adverse Events are reported in the Reported Adverse Event Section. | Baseline through 12 weeks | 
| Change From Baseline in Blood Pressure at 12-Week Endpoint |  | Baseline, 12 weeks | 
| Change From Baseline in Sitting Heart Rate at 12-Week Endpoint |  | Baseline, 12 Weeks | 
| Change From Baseline in Postvoid Residual Volume (PVR) at 12-Week Endpoint | Postvoid residual volume (PVR) is measured by ultrasound at regular intervals. | Baseline, 12 weeks | 
| Change From Baseline in Prostate Specific Antigen (PSA) at 12-Week Endpoint | Measurement of nanograms of PSA per milliliter (ng/mL) of blood. | Baseline, 12 weeks | 
| Change From Baseline in the International Prostate Symptom Score (IPSS) Total Score at 54-Week Endpoint | 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. | Baseline, 54 weeks | 
| Change From Baseline in International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore at 54-Week Endpoint | IPSS storage (irritative) subscore is the sum of Questions 2, 4 and 7 of the IPSS questionnaire. Scores range from 0 (not at all) to 5 (frequent irritative symptoms), thus the 3 questions of the irritative subscore range from 0 to 15. | Baseline, 54 weeks | 
| Change From Baseline in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore at 54-Week Endpoint | IPSS obstructive subscore is the sum of Questions 1, 3, 5 and 6 of the IPSS questionnaire. Scores range from 0 (not at all) to 5 (frequent obstructive symptoms), thus the 4 questions of the obstructive score range from 0 to 20. | Baseline, 54 weeks | 
| Change From Baseline in IPSS Quality of Life (QoL) Index at 54-Week Endpoint | Assessment of quality of life (QOL) by urinary symptoms, with scores ranging from 0 (delighted) to 6 (terrible). | Baseline, 54 weeks | 
| Change From Baseline in Overactive Bladder Symptom Score (OABSS) at 54-Week Endpoint | The OABSS is a four-symptom questionnaire to assess overactive bladder (OAB) symptoms: daytime frequency, nighttime frequency, urgency, and urgency incontinence. Scores range from 0 - 15, with higher scores indicating more severe OAB symptoms. | Baseline, 54 weeks | 
| Change From Baseline in Uroflowmetry Parameter: Peak Flow Rate (Qmax) at 54-Week Endpoint | Uroflowmetry was assessed by Qmax, defined as the peak urine flow rate (measured in mL/second using a standard calibrated flowmeter). | Baseline, 54 weeks | 
| Number of Participants With Adverse Events During 42 Weeks of Open-Label Treatment | A listing of Adverse Events are reported in the Reported Adverse Event Section. | End of 12 weeks of double-blind through 54 weeks | 
| Change From Baseline in Blood Pressure During at 54-Week Endpoint |  | Baseline, 54 weeks | 
| Change From Baseline in Sitting Heart Rate at 54-Week Endpoint |  | Baseline, 54-weeks | 
| Change From Baseline in Prostate Specific Antigen (PSA) at 54-Week Endpoint | Measurement of nanograms of PSA per milliliter (ng/mL) of blood. | Baseline, 54 weeks | 
| Change From Baseline in Postvoid Residual Volume (PVR) at 54-Week Endpoint | Post residual volume (PVR) is measured by ultrasound at regular intervals. | Baseline, 54 weeks |