Vardenafil ODT Versus Placebo in Males With Erectile Dysfunction

Study Overview
=================
Brief Summary
-----------------
This study investigates the safety and efficacy of a new dosage form of Vardenafil, an orodispersible tablet (ODT), and compares it to the safety and efficacy of a placebo (inactive) tablet in the treatment of erectile dysfunction. After a 4-week unmedicated phase, patients will receive Vardenafil ODT or matching placebo for 12 weeks. Safety will be determined by laboratory and other evaluations. Efficacy will be determined by the results of different questionnaires and the patient diary that will be used.

Official Title
-----------------
Pivotal Phase III Trial to Investigate the Efficacy and Safety of an Orodispersible Tablet Vardenafil Versus Placebo in the Treatment of Men With Erectile Dysfunction (ED) - a Fixed-dose, Double-blind, Randomized Multi-center Trial - POTENT I

Conditions
-----------------
Erectile Dysfunction

Intervention / Treatment
-----------------
* Drug: Vardenafil ODT (STAXYN, BAY38-9456)
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males 18 years-of-age or older Stable, heterosexual relationship for at least 6 months A history of erectile dysfunction (ED) for at least 6 months Exclusion Criteria: Any underlying cardiovascular condition, including unstable angina pectoris History of myocardial infarction, stroke or life-threatening arrhythmia within 6 months prior to visit 1 Uncontrolled atrial fibrillation / flutter at screening History of surgical prostatectomy for prostate cancer Hereditary degenerative retinal disorders History of loss of vision because of Non-arteritic anterior ischemic optic neuropathy (NAION), temporary or permanent loss of vision Presence of penile anatomical abnormalities Subjects who have been confirmed with phenylketonuria (PKU) Spinal cord injury Resting or postural hypotension or hypertension Subjects who are taking nitrates or nitric oxide donors, androgens, anti-androgens, alpha- blockers, medication known to prolong QT interval, Human immunodeficiency virus (HIV) protease inhibitors, itraconazole or ketoconazole, an clarithromycin and erythromycin Use of any treatment for ED within 7 days of Visit 1 History of congenital QT prolongation History of syncope within the last 6 months prior to entry into the study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vardenafil ODT (STAXYN, BAY38-9456)<br>Vardenafil 10 mg orodispersible tablet (ODT) taken on demand (PRN), approximately one hour before start of sexual activity, no more than one dose per day. | Drug: Vardenafil ODT (STAXYN, BAY38-9456)<br>* Subjects will receive 12 weeks of PRN (on demand) treatment with Vardenafil 10mg orodispersible tablet (ODT)<br>|
| Placebo Comparator: Placebo<br>Matching placebo tablet taken on demand (PRN), approximately one hour before start of sexual activity, no more than one dose per day. | Drug: Placebo<br>* Subjects will receive 12 weeks of PRN (on demand) treatment with matching placebo tablet<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in International Index of Erectile Function (IIEF-EF Sub-Score) at 12 Weeks or LOCF | The primary variable was the treatment group difference from baseline to Week 12 or Last observation carried forward (LOCF) of the least square mean difference in the IIEF-EF domain score (1-30 ordinal points, specifying the severity of erectile dysfunction: <=10 'severe'; 11-16 'moderate'; 17-21 'mild to moderate'; 22-25 'mild'; >25 'no ED'). | from baseline up to 12 weeks | 
| Change in Percentage From Baseline in Success of Penetration at 12 Weeks | Sexual encounter profile (SEP) items success rates are the percentage of all valid and successful intercourse attempts (items answered 'yes') in relation to all valid attempts. Here the SEP item refers to the ability to penetrate the partner. | from baseline up to 12 weeks of treatment | 
| Change From Baseline in Success of Erection Maintenance at 12 Weeks | SEP items success rates are the percentage of all valid and successful intercourse attempts (items answered 'yes') in relation to all valid attempts. Here the SEP item refers to the ability to maintain an erection after penetration. | from baseline up to 12 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Achieving Back to Normal Erectile Function | Responders: percentage of subjects achieving an IIEF-EF score > 25. The primary variable was the treatment group difference from baseline to Week 12 or Last observation carried forward (LOCF) of the least square mean difference in the IIEF-EF domain score (1-30 ordinal points, specifying the severity of erectile dysfunction: <=10 'severe'; 11-16 'moderate'; 17-21 'mild to moderate'; 22-25 'mild'; >25 'no ED'). | up to 12 weeks of treatment | 
| Change in Percentage From Baseline in Ability to Obtain an Erection at 12 Weeks | SEP items success rates are the percentage of all valid and successful intercourse attempts (items answered 'yes') in relation to all valid attempts. Here the SEP item refers to the ability to obtain successful erections. | from baseline up to 12 weeks of treatment | 
| Change in Percentage From Baseline in Satisfaction With the Hardness of Erection at 12 Weeks | SEP items success rates are the percentage of all valid and successful intercourse attempts (items answered 'yes') in relation to all valid attempts. Here the SEP item refers to the ability to get satisfactory hardness of erections. | from baseline up to 12 weeks of treatment | 
| Change in Percentage From Baseline in Overall Satisfaction at 12 Weeks | SEP items success rates are the percentage of all valid and successful intercourse attempts (items answered 'yes') in relation to all valid attempts. Here the SEP item refers to overall satisfactory attempts. | from baseline up to 12 weeks of treatment | 
| Change in Percentage From Baseline in Ability to Ejaculate at 12 Weeks | SEP items success rates are the percentage of all valid and successful intercourse attempts (items answered 'yes') in relation to all valid attempts. Here the SEP item refers to the ability to have successful ejaculations. | from baseline up to 12 weeks of treatment | 
| Number of Sexual Attempts Till First Successful Attempt |  | up to 12 weeks of treatment | 
| Change From Baseline in Ease With Erection at 12 Weeks or LOCF | Treatment group difference in points on the Treatment Satisfaction Scale (TSS, 0-100 normalized ordinal scores, higher scores indicate greater levels of 'ease with erection', 'erectile functioning satisfaction', 'pleasure of sexual activity', 'satisfaction with orgasm', 'confidence for completion', and 'satisfaction with medication') domain Ease with Erection from baseline to Week 12 or LOCF expressed as the least square mean difference. | from baseline up to 12 weeks | 
| Change From Baseline in Erectile Function Satisfaction at 12 Weeks or LOCF | Treatment group difference in points on the Treatment Satisfaction Scale (TSS, 0-100 normalized ordinal scores, higher scores indicate greater levels of 'ease with erection', 'erectile functioning satisfaction', 'pleasure of sexual activity', 'satisfaction with orgasm', 'confidence for completion', and 'satisfaction with medication') domain  Erectile function satisfaction from baseline to Week 12 or LOCF expressed as the least square mean difference. | from baseline up to 12 weeks | 
| Change From Baseline in Pleasure of Sexual Activity at 12 Weeks or LOCF | Treatment group difference in points on the Treatment Satisfaction Scale (TSS, 0-100 normalized ordinal scores, higher scores indicate greater levels of 'ease with erection', 'erectile functioning satisfaction', 'pleasure of sexual activity', 'satisfaction with orgasm', 'confidence for completion', and 'satisfaction with medication') domain  Pleasure of sexual activity from baseline to Week 12 or LOCF expressed as the least square mean difference. | from baseline up to 12 weeks | 
| Change From Baseline in Satisfaction With Orgasm at 12 Weeks or LOCF | Treatment group difference in points on the Treatment Satisfaction Scale (TSS, 0-100 normalized ordinal scores, higher scores indicate greater levels of 'ease with erection', 'erectile functioning satisfaction', 'pleasure of sexual activity', 'satisfaction with orgasm', 'confidence for completion', and 'satisfaction with medication') domain Satisfaction with orgasm from baseline to Week 12 or LOCF expressed as the least square mean difference. | from baseline up to 12 weeks | 
| Change From Baseline in Confidence for Completion at 12 Weeks or LOCF | Treatment group difference in points on the Treatment Satisfaction Scale (TSS, 0-100 normalized ordinal scores, higher scores indicate greater levels of 'ease with erection', 'erectile functioning satisfaction', 'pleasure of sexual activity', 'satisfaction with orgasm', 'confidence for completion', and 'satisfaction with medication') domain Confidence for completion from baseline to Week 12 or LOCF expressed as the least square mean difference. | from baseline up to 12 weeks | 
| Satisfaction With Medication at Week 12 or LOCF | Treatment group difference in points on the Treatment Satisfaction Scale (TSS, 0-100 normalized ordinal scores, higher scores indicate greater levels of 'ease with erection', 'erectile functioning satisfaction', 'pleasure of sexual activity', 'satisfaction with orgasm', 'confidence for completion', and 'satisfaction with medication') domain Satisfaction with medication at LOCF expressed as the least square mean difference. | up to 12 weeks | 
| Patient Self Reported Improvement of Erectile Function Under Treatment Using a Categorical Rating Scale | Categorical Rating Scale is a binary rating scale with 2 response options which is 'yes/no'; percentage of participants with positive answers to the Global Assessment Question. Global Assessment Question (GAQ): 'Has the treatment you have been taking over the past for weeks improved your erection?' (yes/no) | up to 12 weeks of treatment | 
| Pharmacokinetics Measured as Area Under Curve (AUC) of Vardenafil in Plasma | Plasma concentrations after single dose administration of 10 mg Vardenafil ODT followed for up to 24 hours post-dose. | Visit 5 after 12 weeks of treatment | 
| Pharmacokinetics Measured as Maximum Concentration (Cmax) of Vardenafil in Plasma | Plasma concentrations after single dose administration of 10 mg Vardenafil ODT followed for up to 24 hours post-dose. | Visit 5 after 12 weeks of treatment | 
| Pharmacokinetics Measured as Area Under Curve (AUC) of Metabolite M-1 (BAY44-5576) in Plasma | Plasma concentrations after single dose administration of 10 mg Vardenafil ODT followed for up to 24 hours post-dose. | Visit 5 after 12 weeks of treatment | 
| Pharmacokinetics Measured as Maximum Concentration (Cmax) of Metabolite M-1 (BAY44-5576) in Plasma | Plasma concentrations after single dose administration of 10 mg Vardenafil ODT followed for up to 24 hours post-dose. | Visit 5 after 12 weeks of treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Erectile Dysfunction