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 | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059617 |
E.1.2 | Term | Overactive bladder |
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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 effect of fesoterodine on OAB symptom improvement, vs. placebo, as an “add-on” therapy, in men with persistent OAB symptoms of urinary frequency and urgency with/without urgency incontinence who are receiving alpha-blocker monotherapy for lower urinary tract symptoms (LUTS) at a stable dose for at least 6 weeks. |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the effect of “add-on” fesoterodine on international prostate symptom scale (IPSS) vs. placebo. 2. To evaluate the effect of “add-on” fesoterodine on patient reported outcomes, vs. placebo. 3. To evaluate the safety and tolerability of “add-on” fesoterodine. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Men aged 40 years and above 2. On a stable and well-tolerated dose of an alpha-blocker prescribed for LUTS for at least 6 weeks prior to screening (Visit 1) 3. Persistent symptoms of OAB as verified by the screening 3-day bladder diary, defined by: a. Mean urinary frequency ≥8 times/24 hours b. Mean number of micturition-related urgency episodes ≥3 episode/24 hours (with a Urinary Sensation Scale rating of ≥3 marked for the corresponding micturition in the bladder 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 bladder diary and various questionnaires, comply with scheduled visits and 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. |
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E.4 | Principal exclusion criteria |
1. Any condition that would contraindicate their usage of fesoterodine including: hypersensitivity to the active substance (fesoterodine fumarate) or to peanut or soya or any of the excipients, urinary retention, gastric retention, uncontrolled narrow angle glaucoma, myasthenia gravis, severe hepatic impairment (Child Pugh C), severe ulcerative colitis, and toxic megacolon 2. Poor tolerability to the ongoing alpha blocker treatment or deemed unsuitable or unlikely to continue alpha blocker treatment at the current dose for the duration of the study by the investigator according to the approved product labeling for each drug in each country 3. Previous history of acute urinary retention requiring catheterization or existing clinically significant bladder outlet obstruction in the judgment of the investigator 4. A post void residual urinary volume greater than 200 ml at Baseline (Visit 2) 5. Clinically significant hepatic or renal disease, and/or with a screening test of AST, ALT, Alk Phos, urea nitrogen, or creatinine greater than 1.5 times of the upper limit of normal (ULN) 6. Known history or evidence at screening visit of symptomatic postural hypotension or syncope while on alpha blocker(s) (a measured reduction of greater than 20 mmHg in systolic blood pressure or 10 mmHg in diastolic blood pressure on standing with relevant postural symptoms) 7. History, evidence or suspicion of prostate cancer. A total prostate specific antigen (total PSA) value of greater than 10 ng/ml at screening would exclude subjects, unless documented evidence can be provided to rule out prostate malignancy 8. Neurologic conditions such as stroke, multiple sclerosis, spinal cord injury, or Parkinson’s disease 9. 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 10. A known history of uninvestigated hematuria, interstitial cystitis, genitourinary tuberculosis, bladder calculi or detrusor-sphincter dyssynergia 11. History of radiation treatment to pelvic organs or external genitalia for any reason 12. Previous history of prostatic surgery/intervention (including minimally invasive treatments), or other major urethral and/or bladder surgery 13. Urinary tract infection (UTI) as shown by the results of the urinalysis at Screening or recurrent UTI defined as treatment for UTI >3 times in the last year 14. Treatment with potent CYP3A4 inhibitors, such as clarithromycin, ketoconazole, and itraconazole within 2 weeks prior to Visit 1, or the expectation to start such a treatment during the trial 15. Treatment with hepatic enzyme inducers, eg, barbiturates, rifampicin, carbamazepine, phenytoin, primidone, or St. John’s Wort, within 2 weeks prior to Visit 1, or the expectation to start such a treatment during the trial 16. Treatment with the following medications within 3 weeks prior to Visit 1, or the expectation to start such a treatment during the trial • Any drug treatment for overactive bladder, including antimuscarinic OAB medications • Any drugs with significant anticholinergic or antispasmodic effects 17. Treatment with a 5-alpha reductase inhibitor initiated within 6 months prior to Screening (Visit 1), or the expectation to start such a treatment during the trial 18. Treatment with any medication for BPH other than alpha blocker and 5-alpha reductase inhibitor, eg, saw palmetto, if started less than 4 weeks prior to Visit 1, or the expectation to start such a treatment during the trial 19. Treatment with tricyclic or tetracyclic antidepressant initiated within 4 weeks prior to Visit 1, or on intermittent or unstable use, or the expectation to start such a treatment during the trial 20. Treatment with diuretics initiated within 2 weeks prior to Visit 1, or on intermittent or unstable use, or the expectation to start such a treatment during the trial 21. Use of any electrostimulation, or a formal program of bladder training or pelvic floor exercises under the supervision of a physician or other medical provider within 4 weeks of Visit 1 or the expectation to start such a program during the trial 22. Use of an indwelling catheter or an intermittent self-catheterization program 23. Participation in any clinical trial or receipt of any investigational drug within 4 weeks prior to Visit 1, or the expectation to start such a drug during the trial 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 have any medical 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 26. Subjects who, in the opinion of the investigator, are not likely to complete the study for whatever reason. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Numeric change of micturition-related urgency episodes per 24 hours at Week 12 relative to baseline (micturition-related urgency episodes are defined as those with Urinary Sensation Scale rating of ≥3 marked for the corresponding micturition in the diary) |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 80 |
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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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 | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |