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 (BPH). |
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E.1.1.1 | Medical condition in easily understood language |
Lower urinary tract symptoms associated with prostate gland enlargement. |
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E.1.1.2 | Therapeutic area | Body processes [G] - Physical Phenomena [G01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10004446 |
E.1.2 | Term | Benign prostatic hyperplasia |
E.1.2 | System Organ Class | 10038604 - Reproductive system and breast disorders |
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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 the safety and tolerability of long-term treatment of fixed dose combinations of tamsulosin OCAS 0.4 mg and solifenacin (6 mg and 9 mg) in male subjects with LUTS associated with BPH with a substantial storage component. |
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E.2.2 | Secondary objectives of the trial |
To assess the efficacy of long-term treatment of fixed dose combinations of tamsulosin OCAS 0.4 mg and solifenacin (6 mg and 9 mg) in male subjects with LUTS associated with BPH with a substantial storage component. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Completion of 12 weeks double-blind treatment in Study 905-CL-055.
2. Written informed consent has been obtained.
3. Subject is willing and able to complete the micturition diary and questionnaires correctly. |
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E.4 | Principal exclusion criteria |
1. Any significant PVR (>150 mL).
2. Known history or diagnosis of any of the following urinary conditions:
- Recurrent symptomatic urinary tract infection defined as two or more episodes of such infection occurring in the preceding 12 months
- Urological Pain Syndromes as classified by the European Association of Urology (EAU) Guideline on Chronic Pelvic Pain, up-date 2008, such as interstitial cystitis including bladder pain syndrome, urethral pain syndrome, penile pain syndrome, prostate pain syndrome, scrotal pain syndrome, testicular pain syndrome, post-vasectomy pain and epididymal pain syndrome
- Chronic prostatitis comprising type A (inflammatory) and type B (noninflammatory)
- Evidence of current symptomatic or asymptomatic urolithiasis
- Previous or current malignant disease of the pelvic and urogenital organs with the exception of carcinoma of bladder if longer than 5 years recurrence-free
- Previous pelvic radiation therapy
- Previous surgery to the bladder neck or prostate
- Bladder neck stenosis
- Urethral stricture
3. Narrow angle glaucoma, myasthenia gravis, severe gastrointestinal condition (including toxic megacolon), hiatal hernia, gastroesophageal reflux or subjects at risk for these conditions, urinary or gastric retention or any other medical condition, which in the opinion of the investigator presents a contraindication for the use of anticholinergics.
4. Any other cardiovascular or cerebrovascular diseases such as a clinically relevant history of orthostatic hypotension, which in the opinion of the investigator makes the subject unsuitable for participation in the study.
5. Use of prohibited concomitant medication:
- Other pharmacological treatment used for LUTS/BPH, such as alpha-adrenoceptor (α-AR)-antagonists, plant extracts and 5α-reductase inhibitors.
- Other drugs which may influence the pharmacodynamic effects of solifenacin or tamsulosin, anticholinergics, or cytochrome P450 (CYP) 3A4 inhibitors or inducers that may influence the PK of solifenacin or tamsulosin.
6. Use of combined α/ß-AR-antagonists, α2-agonists, oral and systemic β-agonists, cholinergics and any drugs with cholinergic or anticholinergic side effects, or diuretics. However, long term therapy (>1 month prior to randomization in Study 905-CL-055) with a stable dose of these drugs is permitted. Phosphodiesterase type 5 (PDE5) inhibitors are only permitted on demand for erectile dysfunction.
7. Diabetic neuropathy.
8. Planned cataract surgery during the study or within 30 days after completion of the study.
9. Severe renal impairment (including hemodialysis) or moderate or severe hepatic impairment.
10. Any clinically significant condition, which in the opinion of the investigator makes the subject unsuitable for the trial.
11. Employee of the Astellas Group, the Contract Research Organizations (CROs) involved, or the investigator site executing the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence, severity and relationship of AEs to the study drug
Vital signs
ECG parameters
Laboratory parameters (including hematology, biochemistry, urinalysis and urine culture)
Physical examination
PVR volume
Qmax and Qmean
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Incidence, severity and relationship of AEs to the study drug: Visits 5B, 6, 7, 8 and 9.
Vital signs: Visits 6, 7, 8 and 9.
ECG parameters: Visits 6, 7, 8 and 9 (plus unscheduled visits if necessary).
Laboratory parameters (including hematology, biochemistry, urinalysis and urine culture): Sample collection at visits 6, 7, 8 and 9/premature termination of treatment for evaluation by central laboratory).
Physical examination: At visit 9 or at last visit if subject withdraws prematurely from study.
PVR volume: Visits 6, 7, 8 and 9.
Qmax and Qmean: : Visits 6, 7, 8 and 9.
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E.5.2 | Secondary end point(s) |
Efficacy Variables:
● Change from baseline (Visit 2 of Study 905-CL-055) to endpoint in total I-PSS
● Change from baseline (Visit 2 of Study 905-CL-055) to endpoint in TUS (from
micturition diary)
Change from baseline (Visit 2 of Study 905-CL-055) to endpoint in:
From micturition diary:
● Mean number of micturitions per 24 hours
● Mean volume voided per micturition
● Maximum volume voided per micturition
● Mean number of urgency episodes (PPIUS grade 3 or 4) per 24 hours
● Mean number of urgency incontinence episodes per 24 hours
● Mean number of incontinence episodes per 24 hours
● Mean number of nocturia episodes per 24 hours
● Mean number of pads used per 24 hours
From I-PSS questionnaire:
● I-PSS voiding scores
● I-PSS storage scores
● I-PSS QoL scores
● Individual I-PSS item scores
Other variables:
● OAB Questionnaire (OAB-q) (total and subscores)
● EQ-5D
● Increase/decrease in solifenacin dose
● Reason for dose change
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 131 |
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 | No |
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 |
Austria |
Belarus |
Belgium |
Czech Republic |
France |
Germany |
Hungary |
Italy |
Netherlands |
Poland |
Slovakia |
United Kingdom |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |