| 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 |
|
| 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 |
|
| 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. |
|
| E.2.2 | Secondary objectives of the trial |
•Safety and the tolerability of the combination of different doses of solifenacin succinate (0, 3, 6 and 9 mg) and tamsulosin OCAS (0 and 0.4 mg)
•Dose response relationship of the combination of different doses of solifenacin succinate (0, 3, 6 and 9 mg) and tamsulosin OCAS (0 and 0.4 mg) in relieving voiding and storage symptoms
•Efficacy of the combination of solifenacin succinate (3, 6, 9 mg) and tamsulosin OCAS 0.4 mg compared with solifenacin succinate (3, 6, 9 mg) alone
•Pharmacokinetics of the combination of different doses of solifenacin succinate (0, 3, 6 and 9 mg) and tamsulosin OCAS (0 and 0.4 mg)
•Exposure (AUC) response relationship of the combination of different doses of solifenacin succinate (0, 3, 6 and 9 mg) and tamsulosin OCAS (0 and 0.4 mg) in relieving voiding and storage symptoms
|
|
| 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.
8. Patient continues to meet all inclusion criteria of visit 1. |
|
| E.4 | Principal exclusion criteria |
At study entry:
1. Any significant post void residual volume (PVR > 200 mL) (at least 2 assessments to be performed).
2. Evidence of a symptomatic urinary tract infection or a known history or diagnosis of any of the following urinary conditions:
- Recurrent 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. Narrow angle glaucoma, myasthenia gravis, severe gatro-intestinal condition (including toxic megacolon) or patients at risk for these conditions, 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 BPH or overactive bladder, including electrostimulation therapy at the start of 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, 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, oral beta2-agonists or PDE 5 inhibitors (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. A planned cataract surgery within 30 days after completion of the study.
10. Severe renal impairment (including hemodialysis) or moderate or severe hepatic impairment.
11. Known or suspected hypersensitivity to solifenacin, other anticholinergics, tamsulosin, other alpha-AR-antagonists, lactose or any of the other inactive ingredients of the study medication.
12. Any clinically significant condition, which in the opinion of the investigator makes the patient unsuitable for the trial.
13. Participation in any clinical trial within 30 days (or the limit set by national law, whichever is longer) prior to randomization.
14. Employees of the Astellas Group, the CROs involved, or the investigator site executing the study.
At randomization:
15. Patient did not complete the micturition diary or I-PSS questionnaire according to the instructions.
16. Total daily urine volume > 3000 mL as verified in the micturition diary.
17. Any clinically significant abnormal ECG, which in the opinion of the investigator makes the patient unsuitable for the trial.
18. ALAT, ASAT or creatinine outside 2 times the normal range, gamma GT outside 3 times the normal range.
19. 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.
20. Patient fulfils any exclusion criteria of visit 1
|
|
| 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 number of urgency episodes of grade 3 or 4 per 24 hours (PPIUS)
- Mean level of urgency (PPIUS)
- Mean volume voided per micturition
- Mean number of nocturia episodes per 24 hours
other assessments:
- Symptom and bother scores as assessed by ICIQ-MLUTS questionnaire
- PPBC
- VAS-TS
- Qmax
|
|
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 100 |
| 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 |
|
| 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
|
| last visit of the last subject undergoing the trial |
|
| 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 |
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