E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Bexiga Hiperactiva (hiperactividade do detrusor)
Overactive bladder (detrusor overactivity) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059617 |
E.1.2 | Term | Overactive bladder |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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.
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Male and female patients aged ≥18 years. Women must either be aged ≥ 55 years being menopausal since at least 12 months, or must use an adequate birth control method (Note: as adequate method of birth control hormonal contraception, sterilization, spiral/IUD or sexual abstinence is recommended. Furthermore, doublebarrier methods consisting of two of the following measures may be considered at the discretion of the investigator: male or female condom with spermicidal gel, diaphragm, sponge, cervical cap). •Diagnosis of Overactive Bladder (OAB), with and without urge incontinence, for at least six months prior to Visit 1 •At least one out of the three criteria below (to be assessed at Visit 2): * Entire bladder capacity (= maximum cystometric bladder capacity) ≤ 300 mL. OR * In accordance with 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. •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 on average over all days documented: - at least 8 micturitions per day and -at least 1 urgency episode per day * Each patient must document a minimum of 3 consecutive days out of 7 days. •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
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E.4 | Principal exclusion criteria |
Conc. Medic. •Treat. with drugs known to affect urinary bladder function (e.g. anticholinergics, antispasmodics, serotonin-noradrenalin-reuptake-inhibitors) 21 d. prior to V.2 and at any time during study •Treat. with solifenacin 28 d. prior to V. 2 and at any time during study •Treat. with botulinum toxin, capsaicin or resiniferatoxin in the last 6 months prior to V. 2 and at any time during study •Use of cholinergic agonists and cholinesterase inhibitors, e.g. bethanecol, donepezil, rivastigmine •Subj. who are taking nitrates or nitric oxide donors •Use of PDE5 inhibitors within 7 d. prior to V.1 •Pts on alpha-blockers •Subj. 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. • Treat. with acenocumarol or heparin. • Treat. with drugs known to prolong the QT interval, eg Class IA (eg quinidine, procainamide) or Class III (eg, amiodarone, sotalol) antiarrhythmic medications • Treat. with androgens Previous or Current Med.Cond. - General •Any unstable med., psychiatric, or substance abuse disorder that in the opinion of the Inv. 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 CV condition including unstable angina pectoris and severe myocardial insufficiency defined as stages III or IV according to the classification of the NY Heart Association (NYHA) •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 < 90 mmHg) or hypertension (a resting systolic blood pressure > 170 mmHg or a resting diastolic blood pressure > 110 mmHg). •Symptomatic postural hypotension within 6 months of V.1 •History of positive test for Hep. B surface antigen (HBsAg) or Hep. C. •Significant active peptic ulceration •Severe chronic or acute liver disease, history of moderate (Child-PughB) 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 Pts with congenital QT prolongation • Pts with left ventricular outflow obstruction, e.g.due to an Aortic valve disorder Prev. or Current Medical Condit. – Urinary Tract •Bladder fibrosis (low compliance and detru. hyporeflexia/hypocontractility), detru.-sphincter-dyssynergia, detru. hyporeflexia/areflexia and bradykinesia/tremor of the external urethral sphincter •Males with post-void residual (PVR) urinary volume >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 inv. 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 inv. •Any urogenital surgery (including thermotherapy, ultrasound or laser therapy of the prostate, prostatectomy, hysterectomy, incontinence surgery) within 12 months prior to V.1 •Bladder or prostate biopsy 30 d. prior to V.1 •Instrumentation of the lower urinary tract (including cystoscopy, urodynamics) within 14 d. prior to V. 1 •Any history of pelvic radiation therapy •Indwelling catheter •Any history of carcinoma of the urogenital tract • Urolithiasis Abnormal Lab Values •ALT or AST > 3 x upper normal limit •Serum Creatinine > 3.0 mg/dl • Serum creatinine clearance (calculated) < 30.0 ml/min Other Excl. •Particip. in a bladder-training program or any electro stimulation therapy within the 2 weeks prior to V.1 or at any time during the study •Patients who have received any investigational drug (including placebo) within 30 days prior to V.1 •Subj. with known hypersensitivity to vardenafil, BAY 38-9456 (also known as SB-782528) or any component of the investigational medication •Subj. who, in the opinion of the inv., would be non-compliant with the visit schedule of study procedures •Subj. unwilling or unable to independently complete the micturition diary or questionnaires. •Subj. illiterate or unable to understand the micturition diary or questionnaires. •Pregnant or breast-feeding women; women of childbearing potential not using adequate birth control methods.
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E.5 End points |
E.5.1 | 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.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 73 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 9 |