Overactive bladder (detrusor overactivity) MedDRA version: 9.1 Level: LLT Classification code 10059617 Term: Overactive bladder
Conditions
Interventions
Trade Name: LEVITRA
Product Name: vardenafil HCL
Product Code: BAY 38-9456
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: vardenafil
CAS Number: 224785-91-5
Current Sponsor code: Bay 38-
Sponsors
Bayer Healthcare AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Male patients aged > 18 years and female patients aged > 50 years (all post-menopausal) •Diagnosis of Overactive Bladder (OAB), with and without urge incontinence, for at least six months prior to Visit 1 •Entire bladder capacity (= maximum cystometric bladder capacity) 10 cm H2O. This criterion will be assessed at Visit 2. •Detrusor contraction during filling phase leading to involuntarily initiated micturition before a normal bladder capacity is reached. This criterion will be assessed at Visit 2. •Symptoms of OAB are to be assessed during the unmedicated run-in by a 7-day micturition diary (in-between Visits 1 and 2). Each patient must show o at least 8 micturitions per day and o at least 1 urgency episode per day • Patients capable of understanding the given information and having signed and dated written Patient Informed Consent Form after full discussion of the research nature of the treatment and its risks and benefits •Patients able to swallow the study medication in accordance with the protocol Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Concomitant Medication •Treatment with drugs known to affect urinary bladder function (e.g. anticholinergics, antispasmodics, serotonin-noradrenalin-reuptake-inhibitors) 21 days prior to Visit 2 and at any time during the study •Treatment with solifenacin 28 days prior to Visit 2 and at any time during the study •Treatment with botulinum toxin, capsaicin or resiniferatoxin in the last 6 months prior to Visit 2 and at any time during the study •Use of cholinergic agonists and cholinesterase inhibitors, e.g. bethanecol, donepezil, rivastigmine •Subjects who are taking nitrates or nitric oxide donors •Use of PDE5 inhibitors within 7 days prior to Visit 1 •Patients on alpha-blockers •Subjects who are taking the following potent inhibitors of cytochrome P450 3A4: HIV protease inhibitors such as ritonavir or indinavir, the anti-mycotic agents itraconazole and ketoconazole (topical forms are allowed) or erythromycin or clarithromycin. Previous or Current Medical Conditions - General •Any unstable medical, psychiatric, or substance abuse disorder that in the opinion of the Investigator is likely to affect the subject's ability to complete the study or precludes the subject’s participation in the study •Loss of vision in one eye because of non-arteritic anterior ischemic optic neuropathy (NAION) •Hereditary degenerative retinal disorders such as retinitis pigmentosa •Any severe cardiovascular condition including unstable angina pectoris •History of myocardial infarction, stroke or life-threatening arrhythmia within the prior 6 months. •Uncontrolled atrial fibrillation/flutter at screening (ventricular response rate = 100 bpm). •Resting hypotension (a resting systolic blood pressure of 170 mm Hg or a resting diastolic blood pressure > 110 mm Hg). •Symptomatic postural hypotension within 6 months of Visit 1 •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 such as sickle cell anemia, multiple myeloma and leukemia •History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin. •Bleeding disorder Previous or Current Medical Conditions – Urinary Tract •Low compliance bladder (Compliance 150 mL at Baseline •Urinary retention or clinically significant bladder outlet obstruction as determined by the investigator •Chronic persistent local pathology that in the opinion of the investigator may lead to urinary symptoms, such as one of the genito-urinary pain syndromes, interstitial cystitis •Unexplained macro- and micro-hematuria, as determined by the investigator •Any urogenital surgery (including thermotherapy, ultrasound or laser therapy of the prostate, prostatectomy, hysterectomy, incontinence surgery) within 12 months prior to Visit 1 •Bladder or prostate biopsy 30 days prior to Visit 1 •Instrumentation of the lower urinary tract (including cystoscopy, ur
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: In addition to other variables derived from the urodynamic measurements and the micturition diary, a Quality of Life-questionnaire will be used. Population pharmacokinetics will be performed by correlating the treatment effect as determined through urodynamics with the plasma levels of vardenafil.;Primary end point(s): Change from baseline in bladder volume at first detrusor contraction, demonstrated on urodynamic measurements (filling cystometry and pressure flow investigations) at Week 6 (in absolute values). Co-primary target variable will be the change in the number of daily micturitions as reported in the patient diaries. Because of the rather demanding and cumbersome urodynamic examinations which have to be conducted at baseline and end of study recruitment may be difficult. As outlined in Chapter 6.2 sample size adjustments in terms of increased screening numbers are defined. If actual patient enrollment and dropout rates endanger the pre-planned study objectives because of poor recruitment the sequence of the primary efficacy variables will be changed. Under these conditions the primary efficacy variable will be the number of diary-documented micturitions and the volume at first detrusor contraction will be analyzed in a second step provided the micturition data show a significant superiority in favour of vardenafil. ;Main Objective: To determine the therapeutic effect of vardenafil on Overactive Bladder by means of urodynamic measurements (filling cystometry and pressure flow investigations). In addition, a micturition diary will be used. | — |
Countries
Belgium, Czech Republic, France, Germany, Hungary, Netherlands, Portugal, Spain
Outcome results
None listed