| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Treatment of overactive bladder with symptoms of frequency, urgency, and urgency
incontinence. |
|
| 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 |
|
| 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 compare the efficacy of fesoterodine to placebo and tolterodine ER in subjects with overactive bladder after 12 weeks of treatment. |
|
| E.2.2 | Secondary objectives of the trial |
1. To compare the effect of fesoterodine to placebo on patient reported outcomes in subjects with overactive bladder after 12 weeks of treatment.
2. To compare the efficacy of fesoterodine 4mg QD to placebo in subjects with overactive bladder after 1 week of treatment.
3. To summarize safety data for 12 weeks of treatment with either fesoterodine, tolterodine, or placebo in subjects with overactive bladder. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subjects must meet all of the following inclusion criteria to be eligible for enrolment into the trial:
1. Male or female outpatients ≥ 18 years old.
2. Overactive bladder symptoms (subject-reported) for ≥ 3 months prior to
screening/enrolment visit (visit 1).
3. Reported at least an average of 1 UUI episode per 24 hours in the 3-day micturition diary prior to the randomization/baseline visit (visit 2).
4. Mean urinary frequency of ≥ 8 micturitions per 24 hours as verified by the micturition diary prior to randomization/baseline visit (visit 2).
5. Able and willing to complete the micturition diaries and all trial related questionnaires and comply with scheduled clinic visits and clinical trial procedures.
6. Capability of understanding and having signed the informed consent form after full
discussion of the research nature of the treatment and its risk and benefits. |
|
| E.4 | Principal exclusion criteria |
Subjects presenting with any of the following will not be included in the trial:
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. Clinically significant hepatic or renal disease, and/or with a screening test of AST, ALT, ALP, urea nitrogen, or creatinine greater than 1.5 times of the upper limit of normal range (ULN).
3. Neurologic conditions such as stroke, multiple sclerosis, spinal cord injury, or
Parkinson’s disease.
4. Stage 3 or greater pelvic organ prolapse defined as tissue visible through introitus in lithotomy position at rest (without increase in intra abdominal pressure).
5. History of lower urinary tract surgery (e.g., incontinence surgery or surgery to reduce prostate size) within the past 6 months.
6. A known history of interstitial cystitis or a significant pain component associated with OAB symptoms, uninvestigated hematuria, urogenital cancer, interstitial or external radiation to the pelvis or external genitalia, or 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, radiation cystitis, genitourinary tuberculosis, bladder calculi, or detrusor-sphincter dyssynergia.
7. Previous history of acute urinary retention requiring catheterization, or severe voiding difficulties in the judgment of the investigator, prior to baseline.
8. Use of an indwelling catheter or an intermittent self-catheterization program.
9. Symptoms of incontinence being predominately stress urinary incontinence as
determined by the investigator.
10. Polyuria (>3000mL/24h) or a voided volume >500mL for any micturition during the runin period.
11. Urinary tract infection (UTI) as shown by the results of the urinalysis at Screening or recurrent urinary tract infection (RUTIs) defined as treatment for UTI >3 times in the last year.
12. Use of any electrostimulation, bladder training, or pelvic floor exercises (with certified incontinence practitioners) within 4 weeks of visit 1.
13. Treatment with antimuscarinic OAB medication within 2 weeks prior to visit 1; the
antimuscarinic OAB medication may include:
• darifenacin, oxybutynin, propiverine, solifenacin, tolterodine, and trospium
14. Expectation of initiating treatment during the trial with:
• Any drug treatment for overactive bladder
• Any drugs with significant anticholinergic, antispasmodic, parasympathetic,
or cholinergic agonistic effects.
15. Intermittent or unstable use of diuretics throughout trial duration. Treatment with
diuretics initiated within 2 weeks prior to visit 1 is not permitted.
16. Treatment with potent CYP3A4 inhibitors, such as azole antifungal agents (eg,
ketoconazole, itraconazole, miconazole), macrolide antibiotics (erythromycin,
clarithromycin), immunosuppressants (cyclosporine), vinblastine, and protease inhibitors, within 2 weeks prior to visit 1 or the expectation to start such a treatment during the trial.
17. Administration of medications capable of inducing hepatic enzyme metabolism or
transport (e.g., 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.
18. Treatment with any investigational drug within 30 days prior to visit 1, or the expectation to start such a treatment during the trial.
19. Alcohol and/or any other drug abuse in the opinion of the investigator.
20. Female subjects who are pregnant, nursing, or with a positive urine pregnancy test or who are intending to become pregnant within 3 months after the completion of the trial.
21. Female subjects of childbearing potential who are heterosexually active but unwilling or unable to use an adequate form of contraception to prevent pregnancy during the trial. Reliable contraceptive methods may include intrauterine devices (IUD), contraceptive pills of combination type, hormonal implants, injectable contraceptives or latex condoms with a spermicide.
22. Subjects who have any medical or psychological condition or social
circumstances that would impair their ability to participate reliably in the trial, or those who may increase the risk to themselves or others by participating.
23. Subjects who, in the opinion of the investigator, are not likely to complete the trial for whatever reason.
24. Tolterodine is a marketed medication in all trial countries. Inclusion & exclusion of patients into the trial should be in compliance with the approved product labelling in each country. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change in mean number of urgency urinary incontinence (UUI) episodes per 24 hours at week 12 relative to the baseline (UUI episodes are defined as those with Bladder Sensation Scale rating of 5 in the diary) |
|
| 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 | 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) | Yes |
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 102 |
| 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
|
| End of Trial in a Member State of the European Union is defined as the time at which it is deemed that sufficient subjects have been recruited and completed the trial as stated in the regulatory application (i.e., Clinical Trial Application (CTA)) and ethics application in the Member State. Poor recruitment (recruiting less than the anticipated number in the CTA) by a Member State is not a reason for premature termination but is considered a normal conclusion to the trial in that Member State. |
|
| 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 | 6 |
| 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 | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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