A Study of Tadalafil Use With Finasteride in Men With Enlarged Prostates and Urinary Symptoms

Study Overview
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Brief Summary
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The purpose of this study is to investigate the efficacy and safety of once daily tadalafil when taken with finasteride as a treatment for men with signs and symptoms of Benign Prostatic Hyperplasia and demonstrable prostate enlargement.

Official Title
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A Phase 3b, Randomized, Double-blind, Placebo-controlled Parallel-design Study to Evaluate the Efficacy and Safety of Tadalafil Co-administered With Finasteride for 6 Months in Men With Lower Urinary Tract Symptoms and Prostatic Enlargement Secondary to Benign Prostatic Hyperplasia

Conditions
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Benign Prostatic Hyperplasia, Enlarged Prostate

Intervention / Treatment
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* Drug: Tadalafil
* Drug: Placebo
* Drug: Finasteride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have not taken the following treatments within the indicated duration and agree not to use at any time during the study: All other Benign Prostatic Hyperplasia (BPH) therapy (including herbal preparations) for at least 4 weeks prior to receiving study medication. Overactive bladder therapy (including antimuscarinics) for at least 4 weeks prior to receiving study medication. Erectile Dysfunction therapy (including herbal preparations) for at least 4 weeks prior to receiving study medication. Finasteride or dutasteride use at any time. Have bladder outlet obstruction as defined by a urinary peak flow rate (Qmax) of greater than or equal to 4 and less than or equal to 15 milliliters (mL)/second before receiving study drug. Have prostate enlargement measured by ultrasound at screening. Exclusion Criteria: 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]. 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 problems with kidneys, liver, or nervous system Have uncontrolled diabetes Have had a stroke or a significant injury to brain or spinal cord. Have scheduled or planned surgery during the course of the 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tadalafil<br> | Drug: Tadalafil<br>* 5 milligrams (mg) administered orally, once daily for 26 weeks<br>* Other names: LY#450190;Drug: Finasteride<br>* 5mg administered orally, once daily for 26 weeks<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Administered orally, once daily for 26 weeks<br>Drug: Finasteride<br>* 5mg administered orally, once daily for 26 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Total International Prostate Symptom Score (IPSS) From Baseline to 12 Weeks | The International Prostate Symptom Score (IPSS) is a rating scale for severity of lower urinary tract symptoms (LUTS). The IPSS has a 7-component questionnaire. Each question is scored on a scale from 0 (none/no symptoms) to 5 (frequent symptoms), for a total score range of 0 to 35. Higher numerical scores from the IPSS questionnaire represent greater severity of symptoms. Least Squares (LS) Mean values were obtained from a mixed model repeated measures (MMRM) analysis. Model includes treatment, region, visit, baseline total IPSS, and visit-by-treatment interaction. | Baseline, 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Total International Prostate Symptom Score (IPSS) From Baseline to 4 and 26 Weeks | The International Prostate Symptom Score (IPSS) is a rating scale for severity of lower urinary tract symptoms (LUTS). The IPSS has a 7-component questionnaire. Each question is scored on a scale from 0 (none/no symptoms) to 5 (frequent symptoms), for a total score range of 0 to 35. Higher numerical scores from the IPSS questionnaire represent greater severity of symptoms. Least Squares (LS) Mean values were obtained from a mixed model repeated measures (MMRM) analysis. Model includes treatment, region, visit, baseline total IPSS, and visit-by-treatment interaction. | Baseline, 4 weeks, 26 weeks | 
| Change in International Prostate Symptom Score (IPSS) Subscores Index From Baseline to 4, 12, and 26 Weeks | IPSS storage (irritative) subscore is the sum of Questions 2, 4 and 7 of the 7-component IPSS questionnaire. Scores range from 0 (no irritative symptoms) to 5 (frequent irritative symptoms), with total subscore of the 3 questions for irritative subscore range from 0 to 15. IPSS voiding (obstructive) subscore is the sum of Questions 1, 3, 5 and 6 of the IPSS questionnaire. Scores range from 0 (no obstructive symptoms) to 5 (frequent obstructive symptoms), with total subscore of the 4 questions of the obstructive score range from 0 to 20. Least Squares (LS) Mean values were obtained from a mixed model repeated measures (MMRM) analysis. Model includes treatment, region, visit, baseline total IPSS, and visit-by-treatment interaction. | Baseline, 4 weeks, 12 weeks, 26 weeks | 
| Change in International Prostate Symptom Score (IPSS) Quality of Life Index From Baseline to 4, 12, and 26 Weeks | IPSS Quality of Life Index assesses participant response to the following question: If you were to spend the rest of your life with your urinary condition just the way it is now, how would you feel about that? Response options are Delighted (0); Pleased (1); Mostly satisfied (2); Mixed-about equally satisfied and dissatisfied (3); Mostly dissatisfied (4); Unhappy (5); Terrible (6), with a total range of 0-6. Least Squares (LS) Mean values were obtained from a mixed model repeated measures (MMRM) analysis. Model includes treatment, region, visit, baseline total IPSS, and visit-by-treatment interaction. | Baseline, 4 weeks, 12 weeks, 26 weeks | 
| Change in International Index of Erectile Function (IIEF) - Erectile Function Domain Scores From Baseline to 4, 12, and 26 Weeks | Self-reported erectile function over the past 4 weeks. IIEF- EF is the sum of Questions 1-5 and 15 of the IIEF. Questions 1-5 are scored 0 (low/no erectile function) to 5 (high erectile function) and Question 15 is scored 1 (very low confidence) to 5 (very high confidence), for a total score ranging from 1 to 30. Higher scores represent better erectile function. Least Squares (LS) Mean values were obtained from a mixed model repeated measures (MMRM) analysis. Model includes treatment, region, visit, baseline IIEF, and visit-by-treatment interaction. | Baseline, 4 weeks, 12 weeks, 26 weeks | 
| Change in International Index of Erectile Function (IIEF) - Overall Satisfaction Domain Scores From Baseline to 4, 12, and 26 Weeks | Self-reported overall satisfaction over the past 4 weeks. IIEF-Overall Satisfaction is the sum of Questions 13 and 14 of IIEF questionnaire. Scores range from 1 (low/no satisfaction) to 5 (high satisfaction) for each question, with the total possible score for the 2 questions ranging from 2 to 10. Higher total scores indicate higher satisfaction. Least Squares (LS) Mean values were obtained from a mixed model repeated measures (MMRM) analysis. Model includes treatment, region, visit, baseline IIEF, and visit-by-treatment interaction. | Baseline, 4 weeks, 12 weeks, 26 weeks | 
| Change in International Index of Erectile Function (IIEF) - Intercourse Satisfaction Domain Scores From Baseline to 4, 12, and 26 Weeks | Self-reported intercourse satisfaction over the past 4 weeks. IIEF-intercourse satisfaction is the sum of Questions 6, 7 and 8 of the IIEF. Scores range from 0 (low/no satisfaction) to 5 (high satisfaction) for each question, with the total possible score for the 3 questions of 0 to 15. Higher total scores indicate higher satisfaction. Least Squares (LS) Mean values were obtained from a mixed model repeated measures (MMRM) analysis. Model includes treatment, region, visit, baseline IIEF, and visit-by-treatment interaction. | Baseline, 4 weeks, 12 weeks, 26 weeks | 
| Change in International Index of Erectile Function (IIEF) - Orgasmic Function Domain Scores From Baseline to 4, 12, and 26 Weeks | Orgasmic Function domain scores is the sum of Questions 9 and 10 from the IIEF questionnaire. Scores range from 0 (low/no orgasm) to 5 (high orgasm) for each question, with the total possible score for the 2 questions ranging from 0 to 10. Higher total scores indicate higher orgasm. Least Squares (LS) Mean values were obtained from a mixed model repeated measures (MMRM) analysis. Model includes treatment, region, visit, baseline IIEF, and visit-by-treatment interaction. | Baseline, 4 weeks, 12 weeks, 26 weeks | 
| Change in International Index of Erectile Function (IIEF) - Sexual Desire Domain Scores From Baseline to 4, 12, and 26 Weeks | Sexual desire domain scores is the sum of Questions 11 and 12 from the IIEF questionnaire. Scores range from 1 (low/no desire) to 5 (high desire) for each question, with the total possible score for the 2 questions ranging from 2 to 10. Higher total scores indicate higher desire. Least Squares (LS) Mean values were obtained from a mixed model repeated measures (MMRM) analysis. Model includes treatment, region, visit, baseline IIEF, and visit-by-treatment interaction. | Baseline, 4 weeks, 12 weeks, 26 weeks | 
| Patient Global Impression of Improvement (PGI-I) at 26 Weeks | Patient Global Impression of Improvement (PGI-I) measures the participant's perception of improvement at the time of assessment compared with the start of treatment. Number of participants is reported by the categorized score ranging from 1 (very much better) to 7 (very much worse). | 26 weeks | 
| Treatment Satisfaction Scale - Benign Prostatic Hyperplasia (TSS-BPH) at 26 Weeks | The TSS-BPH was a validated participant-rated instrument that measured participant satisfaction with treatment based on a 13-item questionnaire. It consists of 10 items on a Likert-like scale with scores ranging from 1 (higher satisfaction) to 5 (lower satisfaction), 1 item with score ranging from 0 (higher satisfaction) to 5 (lower satisfaction), and 2 yes/no questions. The mean score for each participant ranges from 0.9 (higher satisfaction) to 5.0 (lower satisfaction). Data presented are the average of mean scores for each treatment group. | 26 weeks | 
| Clinician Global Impression of Improvement (CGI-I) at 26 Weeks | Clinician Global Impression of Improvement (CGI-I) measures clinician's perception of participant improvement at the time of assessment compared with the start of treatment. Number of participants is reported by the categorized score ranging from 1 (very much better) to 7 (very much worse). | 26 weeks | 
| Change in Post Void Residual (PVR) Volume From Baseline to 26 Weeks | Postvoid Residual Volume (PVR) is determined using a portable, calibrated ultrasound device. It consists of the average of a minimum of 3 scans where the residual bladder volume was calculated by averaging the most accurate of the 3 imaging attempts. | Baseline, 26 weeks | 
| Change in International Index of Erectile Function (IIEF) Question 3 and 4 Scores From Baseline to 4, 12, and 26 Weeks | IIEF Question 3 asks how often a participant was able to penetrate his partner over the past 4 weeks. Scores range from 0 (did not attempt intercourse) to 5 (almost always or always). IIEF Question 4 asks whether/how often a participant was able to maintain an erection after penetration over the past 4 weeks. Scores range from 0 (did not attempt intercourse) to 5 (almost always or always). Least Squares (LS) Mean values were obtained from a mixed model repeated measures (MMRM) analysis. Model includes treatment, region, visit, baseline IIEF, and visit-by-treatment interaction. | Baseline, 4 weeks, 12 weeks, 26 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Benign Prostatic Hyperplasia (BPH), Enlarged Prostate