E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059617 |
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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 evaluate the dose-response relationship of YM178-OCAS on efficacy in patients with OAB |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the safety and tolerability of once daily dosing with YM178-OCAS in patients with OAB. - To compare the efficacy of YM178-OCAS to tolterodine 4 mg qd. - To compare the safety and tolerability of YM178-OCAS to tolterodine 4 mg qd. - To collect population pharmacokinetics data in patients with OAB.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Male or female patient aged ≥ 18 years. 2. Signed informed consent has been obtained. 3. Patient is willing and able to complete the micturition diary and questionnaires correctly. 4. Symptoms of overactive bladder (urinary frequency and urgency with or without incontinence) for ≥ 3 months.
At randomization: 5. Patient must experience frequency of micturition on average ≥ 8 times per 24-hour period during the 3-day micturition diary period. 6. Patient must experience at least 3 episodes of urgency (grade 3 or 4), with or without incontinence, during the 3-day micturition diary period. 7. Patient must still fulfill all inclusion criteria and none of the exclusion criteria from visit 1.
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E.4 | Principal exclusion criteria |
At study entry 1. Breastfeeding women, pregnant women or women who intend to become pregnant during the study or women of childbearing potential who are sexually active and practicing an unreliable method of birth control or will be lactating during the study. Reliable contraceptive methods are intra-uterine devices, contraceptive pills of combination type, hormonal implants, contraceptive patches and injectable contraceptives. 2. Clinically significant outflow obstruction (at the discretion of the investigator). 3. Significant post void residual volume (PVR>200ml). 4. Significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor as determined by the investigator (for female patients confirmed by a cough provocation test). 5. Patients with indwelling catheters or practicing intermittent self-catheterization. 6. Diabetic neuropathy. 7. Evidence of a symptomatic urinary tract infection, chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy or previous or current malignant disease of the pelvic organs. 8. Uncontrolled narrow angle glaucoma, urinary or gastric retention, colitis ulcerosa, toxic megacolon, myasthenia gravis or any other medical condition which in the opinion of the investigator makes the use of anticholinergics contra-indicated. 9. Non-drug treatment including electrostimulation therapy (a bladder training program or pelvic floor exercises which started more than 1 month prior to entry into the study can be continued). 10. Use of medications intended to treat urinary incontinence or listed in Appendix 1 Part A. Part B lists medications that are restricted but accepted under certain conditions). 11. Known or suspected hypersensitivity to tolterodine, other anticholinergics, ß-adrenoceptor agonists, or lactose or any of the other inactive ingredients. 12. Clinically significant cardiovascular or cerebrovascular diseases within 6 months prior to visit 1, such as myocardial infarction, uncontrolled angina, significant ventricular arrhythmias, sinus tachycardia, heart failure (NYHA class II/IV), orthostatic hypotension, stroke and uncontrolled hypertension, indicated by a sitting systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100mmHg. In addition patients with a heart rate <45 and >100 should be excluded. 13. Any other clinically significant condition, which in the opinion of the investigator makes the patient unsuitable for the study. 14. Participation in any clinical study within 30 (90 in the UK) days prior to randomization. 15. Employees of the Astellas Group, third parties associated with the study, or the study site.
At randomization: 16. Patient who did not complete the micturition diary according to the instructions. 17. Average total daily urine volume > 3000 ml as recorded in the micturition diary. 18. Clinically significant elevation of serum creatinine or liver enzymes as evidenced by creatinine >150 mmol/L, ASAT or ALAT > 2x upper limit of normal range (ULN), γ-GT > 3x ULN and/or abnormal serum total bilirubin (as assessed in visit 1 samples or alternative sampling within 4 weeks prior to visit 1). 19. ECG on visit 1 showing a QTc prolongation>470 msec, patients with risk factors for Torsades de Pointes (NYHA II-IV-see above, hypokaliemia, familial long QT syndrome) and patients receiving co-medication with QT-prolonging drugs. 20. Any other clinically significant abnormal ECG which in the opinion of the investigator makes the patient unsuitable for the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Endpoint
Change from baseline to endpoint in mean number of micturitions/24 h
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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 | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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) | Yes |
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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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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Normal completion of the study - The subject has completed all visits
Subject ended the study prematurely due to any of the reasons below: - Adverse events - Subject died - Protocol violation(s) - Subject Lost to follow up - Lack of efficacy - Withdrawal of consent - Other
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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 | 1 |
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 | 1 |