A Study To Assess If 10 mg Vardenafil (BAY38-9456) Taken Twice Daily For 6 Weeks Has An Effect On Bladder Function

Study Overview
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Brief Summary
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The purpose of this study is to assess if the study drug, Vardenafil (approved by Health Authorities is available on the market for treatment of erectile dysfunction) has an effect on bladder function and micturition frequency. The study drug is to be taken in the form of tablets twice a day, one tablet in the morning and one tablet in the evening. A non-active treatment (placebo), a sugar pill, will be used as a comparator to see if the new study drug works better than no drug. The timing of visits for the study is as follows: the 1st visit (screening visit) at beginning of run-in-assessment with qualifying tests for patients: electrocardiogram (ECG), safety laboratory and residual urine (by ultrasonography: a non-invasive examination using ultrasound for the assessment of the bladder). 2nd visit (randomization visit). During visit this should be performed: urodynamic measurements (filling cystometry and pressure flow investigations), ECG and safety laboratory. 3rd visit (safety visit) takes place at two up to three weeks of randomized treatment. 4th visit (final visit)-following test should be done: urodynamic measurements (filling cystometry and pressure flow investigations), ECG, safety laboratory and residual urine (by ultrasonography); A phone call 24 hours after visit 4 to assess any SAEs.

Official Title
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Randomized, Double-blind, Placebo-controlled, Parallel Group Study of Vardenafil 10 mg Twice Daily to Assess the Effect on Urodynamics in Patients With Overactive Bladder (Detrusor Overactivity)

Conditions
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Overactive Bladder, Detrusor Overactivity

Intervention / Treatment
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* Drug: Vardenafil HCl (Levitra, BAY38-9456)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients aged > 18 years (females either postmenopausal or using adequate birth control) Urodynamic criteria: Entire bladder capacity (= maximum cystometric bladder capacity) < 300 mL OR In accordance with International Continence Society (ICS)-guidelines: Detrusor overactivity as defined as spontaneous involuntary detrusor contraction during filling phase OR Detrusor contraction during filling phase leading to involuntarily initiated micturition before a normal bladder capacity is reached Patient micturition diary criteria: at least 8 micturitions per day AND at least 1 urgency episode per day Signed and dated written Patient Informed Consent Form Exclusion Criteria: Treatment with drugs known to affect urinary bladder function Known other reasons for micturition problems than detrusor overactivity Recent intervention in urogenital tract Abnormal liver or renal lab values Treatment with nitrates or nitric oxide donors, alpha-blockers, potent inhibitors of CYP-450 3A4, acenocoumarol, heparin, drugs known to prolong QT-interval NAION, hereditary regenerative retinal disorders, severe cardiovascular conditions, recent history of myocardial infarction/stroke/life-threatening arrhythmia congenital QT-prolongation, left ventricular outflow obstruction, severe hypo- or hypertension, symptomatic postural hypotension History of positive test for Hepatitis B surface antigen (HBsAg) or Hepatitis C Significant active peptic ulceration Severe chronic or acute liver disease, history of moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment In men: Clinically significant chronic haematological disease which may lead to priapism History of malignancy of any organ system within the past 5 years Bleeding disorder

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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 |
| --- | --- |
| Experimental: Vardenafil HCl (Levitra, BAY38-9456)<br>vardenafil hydrochloride 10 mg film-coated tablets twice daily (BID) for oral (by mouth) intake for 6 weeks | Drug: Vardenafil HCl (Levitra, BAY38-9456)<br>* vardenafil hydrochloride 10 mg film-coated tablets twice daily (BID) for oral (by mouth) intake for 6 weeks<br>|
| Placebo Comparator: Placebo<br>vardenafil hydrochloride-matching film-coated tablets BID for oral intake for 6 weeks | Drug: Placebo<br>* vardenafil hydrochloride-matching film-coated tablets BID for oral intake for 6 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Bladder Volume at First Detrusor Contraction at 6 Weeks | Bladder volume was measure by means of urodynamic assessments (cystometry) for up to 6 weeks. Missing data were imputed with last observation carried forward (LOCF). | baseline and up to 6 weeks of treatment Last Observation Carried Forward (LOCF) | 
| Change From Baseline in Average Number of Daily Micturitions at 6 Weeks | Change from baseline in the number of daily micturitions (bladder voidings), as reported in the participant diaries for up to 6 weeks. Missing data were imputed with last observation carried forward (LOCF). | baseline and up to 6 weeks of treatment LOCF | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in H2O Detrusor Pressure at First Contraction at 6 Weeks | Detrusor pressure was measured by means of urodynamic assessment (cystometry) for up to 6 weeks. Missing data were imputed by last observation carried forward (LOCF). | baseline and up to 6 weeks of treatment LOCF | 
| Change From Baseline in Volume at First Detectable Leakage at 6 Weeks | First detectable leakage was determined by means of cystometry as an obligatory urodynamic measure. Missing data was imputed by last observation carried forward (LOCF). | baseline and up to 6 weeks of treatment LOCF | 
| Change From Baseline in Maximum Cystometric Bladder Capacity at 6 Weeks | Maximum cystometric bladder capacity was defined as the volume at which either significant leakage or discomfort/pain occurred. Missing data were imputed by last observation carried forward (LOCF). | baseline and up to 6 weeks of treatment LOCF | 
| Change From Baseline in Volume at First Desire to Void at 6 Weeks | Volume at first desire to void was recorded during urodynamic assessments. Missing data were imputed by last observation carried forward (LOCF). | baseline and up to 6 weeks of treatment LOCF | 
| Change From Baseline in Average Number of Urgencies Per Day at 6 Weeks | The average number of urgencies was derived from the number of urgencies reported by the participants in a 7 day micturition diary. Missing data were imputed by last observation carried forward. | baseline and up to 6 weeks of treatment LOCF | 
| Change From Baseline in Average Number of Daily Involuntary Discharges of Urine at 6 Weeks | The average number of daily involuntary discharges of urine was derived from the number of discharges reported by the participants in a 7 day micturition diary. Missing data were imputed by last observation carried forward. | baseline and up to 6 weeks of treatment LOCF | 
| Change From Baseline in Peak Urinary Flow at 6 Weeks in Men Aged 50 Years and Older | Peak urinary flow (Qmax) was measured using urodynamic assessments (voiding / flow cystometry) for up to 6 weeks. Missing data were imputed by last observation carried forward (LOCF). | baseline and up to 6 weeks of treatment LOCF | 
| Change From Baseline in the Total Score of the Overactive Bladder Questionnaire (OAB-q) at 6 Weeks | The OAB-q is a validated, self-administered questionnaire that quantifies bladder symptoms and quality of life. It comprises 33 items (6-point scale for each item). The total score ranges from 33 (minimum symptoms) to 198 (maximum symptoms). On each item, participants provide their rating over the past 4 weeks. Missing data were imputed by LOCF. | baseline and up to 6 weeks of treatment LOCF |