E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Overactive Bladder in Men |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020853 |
|
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 additional benefit of ‘Add-On’ tolterodine L-tartrate ER (Detrol LA®), vs. placebo, to alpha-blocker therapy in men with persistent OAB symptoms of urinary frequency and urgency with/without urgency incontinence as assessed by the change in the Patient Perception of Bladder Condition (PPBC) after 12 weeks of treatment. |
|
E.2.2 | Secondary objectives of the trial |
·To evaluate the additional benefit of ‘Add-On’ tolterodine L-tartrate ER (Detrol LA®), vs. placebo, to alpha-blocker therapy in men with persistent OAB symptoms of urinary frequency and urgency with/without urgency incontinence: ·On OAB symptoms as assessed by 5-day voiding bladder diaries including Urinary Sensation Scale ·On symptoms as assessed by the International Prostate Symptom Score (IPSS) ·On patient perception of treatment benefit as assessed by the Patient Perception of Treatment Benefit Questionnaire (PPTB) ·On patient perception of bladder condition as assessed by the change in the PPBC after 4 weeks of treatment ·On bothersome quality of life (QoL) symptoms as assessed by the Overactive Bladder Questionnaire (OAB-q) ·On sexual QoL as assessed by the ICIQ-MLUTSsex Questionnaire |
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the trial: 1. Men aged 40 years and above (with no upper limit of age) 2. On a stable dose of an alpha-blocker for at least 1 month 3. Persistent symptoms of OAB as verified by the screening 5 day micturition diary, defined by: a. Mean urinary frequency ≥8 times/24 hours b. Mean number of urgency episodes, with/without urgency incontinence, ≥1 episode/24 hours (with a Urinary Sensation Scale rating of ≥3 in the micturition diary) 4. A rating of the bladder condition at Baseline (visit 2) prior to randomization as “Some Moderate Problems”, “Severe Problems”, or “Many Severe Problems” on the Patient Perception of Bladder Condition (PPBC) questionnaire 5. The ability and willingness to correctly complete the micturition diary and various questionnaires, comply with scheduled visits and comply with trial procedures 6. The capability of understanding and having signed the informed consent form after full discussion of the research, nature of the treatment, and its risks and benefits |
|
E.4 | Principal exclusion criteria |
Subjects presenting with any of the following will not be included in the trial: 1. Previous history of acute urinary retention requiring catheterization 2. A post void residual urinary volume greater than 200mls at Screening (visit 1) 3. Poor detrusor function or clinically relevant bladder outlet obstruction based on investigator’s judgment as shown in a flow rate and residual volume measurement at Screening (visit 1) 4. A 5-alpha reductase inhibitor if started less than 6 months prior to Screening (visit 1) 5. Urinary tract infection (UTI), including bacterial prostatitis, confirmed by a positive urine test or recurrent UTI defined as being treated for >3 episodes of symptomatic UTI in the past 12 months 6. A known history of bladder outlet obstruction due to: vesical neck contracture, clinical suspicion of prostate carcinoma, mullerian duct cysts, urethral obstruction due to stricture/valves/sclerosis or urethral tumor 7. A known history of uninvestigated haematuria, interstitial cystitis, genitor-urinary tuberculosis, bladder calculi or detrusor-sphincter dyssynergia8. Previous history of prostatic surgery/intervention (including minimally invasive treatments), or other major urethral and/or bladder surgery or if subjects have any AEs requiring prostate surgery/intervention to relieve bladder outlet flow obstruction 9. History or suspicion of prostate cancer including a serum PSA (prostate specific antigen) concentration of greater than 10 ng/ml on repeat testing 10. History of radiation treatment (external or interstitial) to pelvic organs or external genitalia for any reason. 11. Any condition which, in the opinion of the investigator, makes the patient unsuitable, or with contraindications for inclusion, e.g., uncontrolled narrow-angled glaucoma, retention of urine, gastric retention or hypersensitivity to Detrol LA® or any of the ingredients 12. Concomitant overt peripheral and central neurologic diseases, such as spinal cord injury or multiple sclerosis 13. Significant hepatic or renal disease, defined as twice the upper limit of the reference ranges regarding serum concentrations of AST, ALT, ALP, urea nitrogen, or creatinine 14. Expectation of initiating treatment with any other drug for OAB or any drug with significant anticholinergic, antispasmodic, parasympathetic, or cholinergic agonistic effects during the trial 15. Treatment with potent CYP3A4 inhibitors, such as macrolide antibiotics (erythromycin, clarithromycin), immunosuppressants (cyclosporine), azole antifungal agents (i.e., ketoconazole, itraconazole), protease inhibitors, or the expectation to start such a treatment during the trial 16. Administration of medications capable of inducing hepatic enzyme metabolism or transport (e.g., barbiturates, rifampicin, carbamazepine, phenytoin, primidone, or St. John’s Wort) in the past 30 days 17. Use of any electrostimulation or bladder training in the past 30 days 18. Use of an indwelling catheter or an intermittent self-catheterization program 19. Use of any other investigational drug in the past 2 months 20. Treatment with an anti-cholinergic within the past 30 days 21. Intermittent or unstable use of diuretics throughout study duration. Treatment with diuretics initiated within 2 weeks prior to randomization is not permitted 22. A documented record of ≥20 mmHg postural decrease in systolic blood pressure (or) History of postural hypotension or syncope in the judgment of the investigator based on local standards of care 23. Subjects who have any medical (including known history of major hematological, renal, vascular, or hepatic abnormalities) or psychological condition or social circumstances that would impair their ability to participate reliably in the study, or those who may increase the risk to themselves or others by participating 24. Subjects who, in the opinion of the investigator, abuse alcohol or drugs or who have been alcohol- or drug-dependent within the last 6 months 25. Subjects who, in the opinion of the investigator, are not likely to complete the study for whatever reason |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in Patient Perception of Bladder Condition after 12 weeks of double-blind treatment |
|
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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | 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 | 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 |
|
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
|
|
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 | 0 |
E.8.9.1 | In the Member State concerned days | |
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 | 0 |