A Study in Erectile Dysfunction

Study Overview
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Brief Summary
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The purpose of this trial is to evaluate if treatment with tadalafil once daily will allow men to return to normal erectile function in those who did not have normal erectile function following as-needed (PRN) Phosphodiesterase Type 5 (PDE5) Inhibitor treatment.

Official Title
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Tadalafil Once Daily Following As-Needed Phosphodiesterase Type 5 Inhibitor Treatment, an Assessment of Return to Normal Erectile Function

Conditions
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Erectile Dysfunction

Intervention / Treatment
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* Drug: Tadalafil
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least a 3-month history of erectile dysfunction (ED). Are able to read, understand and provide signed informed consent. Have an International Index of Erectile Function-Erectile Function (IIEF-EF) domain score that is greater than or equal to 17 and less than 26 at screening. Have been taking a maximum dose of sildenafil citrate (100 milligram [mg]), vardenafil (20 mg), or tadalafil (20 mg) on as needed basis for at least one month prior to screening. Anticipate having the same female sexual partner during the study who is willing to participate in the required number of sexual intercourse attempts and complete study measures during the study. Agree to make at least four sexual intercourse attempts during both the 4-week as needed run-in period and the 4-week non-drug run-in period. Agree not to use any other erectile dysfunction (ED) treatment, including herbal therapy during the 4-week non-drug, run-in, the double-blind treatment period, the open label period and for 96 hours after the end of the study. Partner Inclusion Criteria: Are female and at least 18 years of age at screening. Anticipate having the same male study subject as her sexual partner during the study. Able to read, understand and provide signed informed consent. Agree to make the required number of sexual intercourse attempts with the male sexual study partner during the study. Willing to participate in recording responses to the treatment satisfaction scale. Exclusion Criteria: Have an IIEF-EF domain score of greater than or equal to 26 at screening. Prior ineffective treatment with (or nonresponder to) any PDE5 Inhibitor Have previously used or are currently using any PDE5 inhibitor once daily. Present with ED caused by other primary disorders or ED caused by untreated/inadequately treated endocrine disease. Partner unwilling to complete all study requirements. History of radical prostatectomy or other pelvic surgery or penile implant, or a clinically significant penile deformity, in the opinion of the investigator Exhibit evidence of clinically significant renal insufficiency or hepatobiliary disease, or significant cardiac history as determined by the investigator Currently receive treatment with nitrates, cancer chemotherapy, or antiandrogens Have previously completed or withdrawn from this study or any other study investigating tadalafil for once-daily use.

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 2.5 milligram (mg) titrated to 5 mg Tadalafil<br>2.5 mg for 4 weeks, followed by 5 mg for 8 weeks with option to continue treatment at 5 mg for an additional 4 weeks | Drug: Tadalafil<br>* Administer orally<br>* Other names: LY450190;|
| Active Comparator: 5 mg Tadalafil<br>5.0 mg for 12 weeks with option to continue treatment for additional 4 weeks | Drug: Tadalafil<br>* Administer orally<br>* Other names: LY450190;|
| Placebo Comparator: Placebo<br>for 12 weeks | Drug: Placebo<br>* Administer orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Having an International Index of Erectile Function - Erectile Function (IIEF-EF) Domain Score Greater Than or Equal to 26 Through 12-Week Endpoint (Double-Blind Treatment Period) | 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. Data presented are the percentage of participants who return to normal erectile function (IIEF-EF domain score ≥26) at end of double-blind treatment period (Period III). | Baseline through 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 12-Week Endpoint in the International Index of Erectile Function - Erectile Function (IIEF-EF) Domain Score | 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 of the change from baseline to endpoint is from an analysis of covariance (ANCOVA). The model included centered-baseline as a covariate and factors of study, treatment group, and pooled site within study, and centered-baseline-by-treatment-group interaction. | Baseline, 12 weeks | 
| Change From Baseline to 12-Week Endpoint in the International Index of Erectile Function - Intercourse Satisfaction (IIEF-IS) Domain Score | Self-reported intercourse satisfaction over the past 4 weeks. IIEF-IS 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. Least Squares (LS) mean of the change from baseline to endpoint is from an analysis of covariance (ANCOVA). The model included centered-baseline as a covariate and factors of study, treatment group, and pooled site within study, and centered-baseline-by-treatment-group interaction. | Baseline, 12 weeks | 
| Change From Baseline to 12-Week Endpoint in the International Index of Erectile Function - Overall Satisfaction (IIEF-OS) Domain Score | Self-reported overall satisfaction over the past 4 weeks. IIEF-OS is the sum of Questions 13 and 14; each question scored as 1 (low/no satisfaction) through 5 (high satisfaction) with total subscore for the 2 questions of 2 to 10. Least Squares (LS) mean of the change from baseline to endpoint is from an analysis of covariance (ANCOVA). The model included centered-baseline as a covariate and factors of study, treatment group, and pooled site within study, and centered-baseline-by-treatment-group interaction. | Baseline, 12 weeks | 
| Change From Baseline to 12-Week in Percentage of Yes Responses to Sexual Encounter Profile (SEP) Questions 1-5 | Assessed was the mean change from baseline in the percentage of Yes responses to the SEP diary Questions 1-5. Least Squares (LS) mean of the change from baseline to endpoint is from an analysis of covariance (ANCOVA). The model included centered-baseline as a covariate and factors of study, treatment group, and pooled site within study, and centered-baseline-by-treatment-group interaction. | Baseline, 12 weeks | 
| Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Patient | The TSS measured participant satisfaction with treatment based on a 13-item questionnaire. The overall score for each of five TSS domains (confidence to complete sexual activity, ease of erection, pleasure from sexual activity, erectile function satisfaction, and satisfaction with orgasm) was converted to a 0-100 scale with higher numbers on the scale indicating greater satisfaction. Least Squares (LS) mean of the change from baseline to endpoint is from an analysis of covariance (ANCOVA). The model included centered-baseline as a covariate and factors of study, treatment group, and pooled site within study, and centered-baseline-by-treatment-group interaction. | Baseline, 12 weeks | 
| Treatment Satisfaction Scale (TSS) - Patient Satisfaction With Medication Score at Week 12 Endpoint | The TSS - patient satisfaction with medication measured participant satisfaction with treatment based on a 13-item questionnaire. The overall score was converted to a 0-100 scale with higher numbers on the scale indicating greater satisfaction. Satisfaction with medication was analyzed using analysis of covariance (ANOVA). The model included factors of study, treatment group, and pooled site within study. | Week 12 | 
| Change From Baseline to 12-Week Endpoint in the International Index of Erectile Function (IIEF) Question 15 (Sexual Confidence) | Self-reported erectile function over the past 4 weeks. Question 15, confidence in the ability to get an erection, is scored from 1 (very low confidence) to 5 (very high confidence). Least Squares (LS) mean of the change from baseline to endpoint is from an analysis of covariance (ANCOVA). The model included centered-baseline as a covariate and factors of study, treatment group, and pooled site within study, and centered-baseline-by-treatment-group interaction. | Baseline, 12 weeks | 
| Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Partner | The TSS measured participant's partner satisfaction with treatment based on a 13-item questionnaire. The overall score for each of five TSS domains (confidence to complete sexual activity, ease of erection, pleasure from sexual activity, erectile function satisfaction, and satisfaction with orgasm) was converted to a 0-100 scale with higher numbers on the scale indicating greater satisfaction. Least Squares (LS) mean of the change from baseline to endpoint is from an analysis of covariance (ANCOVA). The model included centered-baseline as a covariate and factors of study, treatment group, and pooled site within study, and centered-baseline-by-treatment-group interaction. | Baseline, 12 weeks | 
| Treatment Satisfaction Scale (TSS) - Partner Satisfaction With Medication Score at Week 12 Endpoint | The TSS - partner satisfaction with medication measured participant's partner satisfaction with treatment based on a 13-item questionnaire. The overall score was converted to a 0-100 scale with higher numbers on the scale indicating greater satisfaction. Satisfaction with medication was analyzed using analysis of covariance (ANOVA). The model included factors of study, treatment group, and pooled site within study. | Week 12 | 
| Percentage of Participants Having International Index of Erectile Function - Erectile Function (IIEF-EF) Domain Score Greater Than or Equal to 26 From 12 to 16 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. Data presented are the percentage of participants who return to normal erectile function (IIEF-EF domain score ≥26) at end of open-label extension treatment period (Period IV). | 12 weeks through 16 weeks | 
| Change From 12 Weeks to 16 Weeks in Participant's International Index of Erectile Function - Erectile Function (IIEF-EF) Domain Score | 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. | 12 weeks and 16 weeks | 
| Change From Week 12 to Week 16 Percentage of Yes Responses to Sexual Encounter Profile (SEP) Questions 3 | Assessed the percentage of Yes responses to the SEP diary Question 3 Did your erection last long enough for you to have successful intercourse? from Week 12 (end of double-Blind treatment) to Week 16 (end of open-label treatment). | 12 weeks and 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Erectile Dysfunction, ED, Impotence