E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia |
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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 | 10004446 |
E.1.2 | Term | Benign prostatic hyperplasia |
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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 assess whether the combination of solifenacin succinate (3, 6, 9 mg) and tamsulosin OCAS 0.4 mg provides improved efficacy compared to tamsulosin OCAS 0.4 mg alone in males with LUTS associated with BPH. |
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E.2.2 | Secondary objectives of the trial |
• To assess the dose response relationship of various combinations of solifenacin (0 (placebo), 3, 6, and 9 mg) and tamsulosin OCAS (0 (placebo) and 0.4 mg) in relieving voiding and storage symptoms in male patients with LUTS associated with BPH. • To evaluate the pharmacokinetics of tamsulosin and solifenacin in the target patient population. • To assess the exposure (AUC) response relationship of various combinations of solifenacin (0 (placebo), 3, 6, and 9 mg) and tamsulosin OCAS (0 (placebo) and 0.4 mg) in relieving voiding and storage symptoms in male patients with LUTS associated with BPH. • To select one or more doses of solifenacin in combination with tamsulosin OCAS 0.4 mg for further development.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Males with LUTS associated with BPH fulfilling the following criteria: Inclusion criteria
At study entry: 1. Male aged more than 45 years. 2. Written informed consent has been obtained. 3. Patient is willing and able to complete the micturition diary and questionnaires correctly. 4. Voiding symptoms (including incomplete emptying of the bladder, intermittency, weak stream or hesitancy) and storage symptoms (including frequency, urgency or nocturia), diagnosed as LUTS associated with BPH (formerly known as symptomatic BPH) for more than 3 months. 5. A total I-PSS score of more than 13. 6. A maximum urinary flow rate of more than 4.0 mL/s and ≤ 15.0 mL/s, with a voided volume more than 120 mL during free flow (minimum of 2 flows to be performed).
At randomization: 7. A total I-PSS score of more than 13.
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E.4 | Principal exclusion criteria |
At study entry: 1. Significant post void residual volume (PVR > 200 mL) in at least 2 assessments to be performed. 2. A known history or diagnosis of any of the following urinary conditions: - A symptomatic urinary tract infection - Chronic inflammation such as interstitial cystitis - Stone in bladder or urethra - Previous pelvic radiation therapy - Previous or current malignant disease of the pelvic organs - Previous surgery to the bladder neck or prostate - Bladder neck stenosis - Urethral stricture 3. Uncontrolled narrow angle glaucoma, myasthenia gravis, urinary or gastric retention or any other medical condition which in the opinion of the investigator makes the use of anticholinergics contra-indicated. 4. Clinically significant cardiovascular or cerebrovascular diseases within 6 months prior to visit 1, such as myocardial infarction, uncontrolled angina, significant ventricular arrhythmias, heart failure (NYHA class III/IV), a history of orthostatic hypotension or stroke. 5. Non drug treatment for overactive bladder or BPH, including electrostimulation therapy during the year prior to the study or start of a bladder training program during the 2 weeks prior to or during the study. 6. Use of forbidden concomitant medication: • Other pharmacological treatment for BPH, such as alpha-AR-antagonists and plant extracts (within the 2 weeks prior to visit 1). • 5alpha-reductase inhibitors (within the 3 months prior to visit 1). • Other drugs which may influence the pharmacodynamic effects of solifenacin or tamsulosin, combined alpha/beta-AR-antagonists, alpha-agonists, oral beta-agonists, cholinergics or anti-cholinergics or CYP 3A4 inhibitors or inducers. This medication should be discontinued ultimately at visit 1 (see Appendix 1 Part A). 7. Use of any drugs with cholinergic or anticholinergic side effects, diuretics, calcium channel antagonists or PDE 5 inhibitors or beta blockers (see Appendix 1 Part B). However, long term therapy (>1 month prior to randomization) on a stable dosage of these drugs is permissible. 8. Diabetic neuropathy. 9. Severe renal or moderate or severe hepatic impairment. 10. Known or suspected hypersensitivity to solifenacin, other anticholinergics, tamsulosin, other alpha-AR-antagonists, lactose or any of the other inactive ingredients. 11. Any clinically significant condition, which in the opinion of the investigator makes the patient unsuitable for the trial. 12. Participation in any clinical trial within 30 days (90 days in the UK) prior to randomization. 13. Employees of the Astellas Group, the CROs involved, or the investigator site executing the study.
At randomization: 14. Patient did not complete the micturition diary or I-PSS questionnaire according to the instructions. 15. Total daily urine volume > 3000 mL as verified in the micturition diary. 16. Any clinically significant abnormal ECG, which in the opinion of the investigator makes the patient unsuitable for the trial. 17. ALAT/ ASAT or creatinine outside 2 times the normal range, gamma GT outside 3 times the normal range or creatinine ≥4 mg/dl. 18. Any other clinically significant out of the normal range result of urinalysis, biochemistry (including PSA) or hematology, which in the opinion of the investigator makes the patient unsuitable for the trial.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy variable: - Change from baseline to endpoint in total I-PSS score
Secondary efficacy variables: - Change from baseline to endpoint in: From I-PSS questionnaire: - I-PSS voiding scores - I-PSS storage scores - Individual I-PSS item scores - Number of I-PSS responders From micturition diary: - Mean number of micturitions per 24 hrs - Mean number of urge incontinence episodes per 24 hours - Mean number of incontinence episodes per 24 hours - Mean urgency frequency per 24 hours - Mean volume voided - Mean number of nocturia episodes per 24 hours Other assessments: - Symptom and bother scores as assessed by ICIQ-MLUTS questionnaire - PPBC - PPTB - Qmax
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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.8.5 | 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 | 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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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 | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |