A Study of Tadalafil in Benign Prostatic Hyperplasia

Study Overview
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Brief Summary
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The purpose of this study is to investigate the pharmacokinetics of tadalafil in Japanese and non-Japanese men with Benign Prostatic Hyperplasia (BPH). The safety of tadalafil will also be studied.

Official Title
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A Study to Evaluate the Pharmacokinetics of Tadalafil Administered Once Daily in Japanese and Non-Japanese Subjects With Benign Prostatic Hyperplasia

Conditions
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Benign Prostatic Hyperplasia

Intervention / Treatment
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* Drug: Tadalafil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have had lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH-LUTS) (as diagnosed by a qualified physician) >6 months at screening visit. Lower urinary tract symptoms (LUTS) include those associated with voiding (obstructive symptoms, such as incomplete emptying, intermittency, weak stream, straining) and/or storage (irritative symptoms, such as frequency, urgency, nocturia). Have BPH-LUTS with moderate-to-severe symptoms confirmed by an International Prostate Symptom Score (IPSS) >12. (The IPSS total score is defined as the sum of Questions 1 through 7 and does not include the IPSS Quality of Life.) Taking into account the age and disease status, subjects determined to be in good health according to medical history, physical examination, electrocardiogram (ECG), and laboratory safety assessments. Body mass index between 18 and 30 kg/m^2 inclusive. Agree not to use any other approved or experimental pharmacologic BPH, erectile dysfunction (ED), and/or overactive bladder (OAB) treatments, including alpha blockers, phosphodiesterase type 5 (PDE5) inhibitors, or herbal preparations at least 1 week prior to dosing and through to follow-up. Subjects with a serum prostate-specific antigen (PSA) <10.0 ng/mL. Subjects with a serum PSA greater than or equal to 4.0 and <10.0 ng/mL must have documentation of a negative histologic biopsy of carcinoma of the prostate within 12 months prior to screening. Exclusion Criteria: History of radical prostatectomy, or other pelvic surgery or procedure, including any pelvic surgical procedure on the urinary tract apart from transurethral resection, pelvic surgery for malignancy or bowel resection, or a history of lower urinary tract malignancy or trauma. History of urinary retention or lower urinary tract (bladder) stones within 6 months of screening. Current or previous history of malignant disease of the prostate. Concomitant treatment with or ingestion of cytochrome P 450 3A4 (CYP3A4)-inducing or -inhibiting agents from 2 weeks prior to dosing and through the end of the study. Including herbal/food and other supplements, fruit, or fruit juices containing grapefruit or pomegranate components. History of loss of vision in one eye because of nonarteritic anterior ischemic optic neuropathy (NAION), regardless of whether this episode was in connection or not with previous PDE5 inhibitor exposure. Subjects with chronic stable angina treated with long-acting nitrates, subjects with chronic stable angina who required short-acting nitrates in the 90 days prior to screening visit, or subjects with angina occurring during sexual intercourse in the 6 months prior to screening. Subjects having met the criteria for unstable angina within 6 months prior to screening, history of myocardial infarction or coronary artery bypass graft surgery within 90 days prior to screening, or percutaneous coronary intervention (for example, angioplasty or stent placement) within 90 days prior to screening. Any evidence of heart disease (New York Heart Association [NYHA] greater than or equal to Class III) within 6 months of screening. A history of cardiac arrest.

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: Basic Science
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tadalafil<br>5 mg, administered orally, daily for 10 days | Drug: Tadalafil<br>* 5 mg, administered orally, daily for 10 days<br>* Other names: Adcirca;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Area Under the Concentration Curve (AUC) for Tadalafil and Metabolite IC710 | AUC for Day 1 is reported as AUC(tau [t], day 1), which is AUC from time zero to 24 hours (t) postdose on Day 1. AUC for Day 10 is reported as AUC(t,steady state [ss]), which is AUC during one 24-hour dosing interval at steady-state. | 1 day and 10 days | 
| Pharmacokinetics: Concentration Maximum (Cmax) of Tadalafil and Metabolite IC710 |  | 1 day and 10 days | 
| Pharmacokinetics: Time to Concentration Maximum (Tmax) of Tadalafil and Metabolite IC710 |  | 1 day and 10 days |