| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Symptoms and general pathology [C23] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 13.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10059617 |
| E.1.2 | Term | Overactive bladder |
| E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
|
| 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 determine the efficacy of 8 mg fesoterodine on UUI reduction in OAB patients with
suboptimal response to tolterodine over time and in comparison with placebo. |
|
| E.2.2 | Secondary objectives of the trial |
To determine the efficacy of 8 mg fesoterodine on frequency and urgency in OAB
patients with suboptimal response to tolterodine over time and in comparison with
placebo;
To determine the efficacy of 8 mg fesoterodine on quality of life patients reported
outcomes in OAB patients with suboptimal response to tolterodine, over time and in
comparison with placebo;
To determine the tolerability and safety of 8 mg fesoterodine in OAB patients with
suboptimal response to tolterodine. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subject eligibility should be reviewed and documented by an appropriately qualified member of the investigator’s study team before subjects are included in the study.
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
At Screening Visit 1
1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
2. Male or female subjects aged ≥18.
3. Overactive bladder symptoms (subject-reported) for ≥6 months prior to Screening Visit 1
according to ICS guidelines.
4. Rate their bladder condition as “Some Moderate Problems”, “Severe Problems”, or
“Many Severe Problems” on the Patient Perception of Bladder Condition (PPBC)
questionnaire.
5. Female subjects of childbearing potential must not be pregnant, lactating or intending to become pregnant during the course of the study. Those who are heterosexually active must use an adequate form of contraception to prevent pregnancy during the study. Reliable contraceptive methods may include intrauterine devices (IUD), the combined oral contraceptive pill, hormonal implants, injectable contraceptives or latex condoms with a spermicide.
6. Subjects who are willing and able to comply with scheduled visits, the self completion of study questionnaires and symptom diaries, and other study-related activities.
In addition at Visit 2 Eligibility (Week -2)
1. Mean urinary frequency of ≥8 micturitions per 24 hours as verified by the screening
bladder diary.
2. ≥2 and <15 mean UUI episodes per 24 hours prior to Visit 2 (UUI episodes are defined as those with Urinary Sensation Scale rating of 5).
In addition at Visit 3 Randomization (Week 0)
1. Change in mean UUI per 24 hours of ≤50% between Visit 2 and Visit 3. |
|
| E.4 | Principal exclusion criteria |
| 1. Subjects who are investigational site staff members or subjects who are Pfizer employees directly involved in study conduct 2.Any condition that would contraindicate their use of tolterodine or fesoterodine including: hypersensitivity to tolterodine tartrate or fesoterodine fumarate or to peanut, soya or to any of excipients, urinary retention, gastric retention, uncontrolled narrow angle glaucoma, myasthenia gravis, severe hepatic impairment (Child Pugh C), severe ulcerative colitis and toxic megacolon. 3. Conditions or prior treatment that may also affect bladder function: a. Neurologic conditions such as spinal dysraphism, stroke, multiple sclerosis, spinal cord injury, or Parkinson’s disease, which are known or suspected of influencing subject’s bladder function. b. Significant pelvic organ prolapse defined as tissue visible through introitus in lithotomy position at rest, without increase in intra abdominal pressure. c. Symptoms of predominately stress urinary incontinence as determined by investigator. d. Any history of major lower urinary tract/pelvic surgery with permanent or ongoing effects on bladder function. e. A known history of interstitial cystitis/bladder pain syndrome 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, genito-urinary tuberculosis, bladder calculi, or detrusor-sphincter dyssynergia. f. Bladder outlet obstruction evidenced by previous history of acute urinary retention requiring catheterization, use of indwelling catheter or intermittent self-catheterization program, urodynamic evidence of obstruction or severe voiding symptoms and any ongoing clinically significant post-void residual volume of >200 mL. 4.Clinically significant urinary tract infection (UTI) as shown by results of urinalysis at Screening or Visit 2 or recurrent UTI defined as microbiologically proven UTI >3 times in the last year or >2 times in the last 6 months; Urine microscopy, culture and sensitivity testing will be performed in event of symptoms (eg, fever, dysuria), or positive leucocytes, nitrites and/or protein on urinalysis. Re-screening may be performed when UTI has been treated and urine is culture negative, assuming the subject does not subsequently meet the definition for recurrent UTI. 5. Use of any electrostimulation, participation in a formal program of bladder training or pelvic floor exercises under supervision of a physician or other medical provider within 4 weeks of Visit 1; subjects who are already established on a stable therapy should continue with their regimen at a stable level through the course of the study. 6. Treated with the following medications prior to Visit 1 (Screening): (a) Treatment with intra-vesical Botulinum toxin within 6 months of screening (b) Any drugs with significant anticholinergic and antispasmodic effects continuing at screening. Therefore, prior OAB medication should be stopped at Screening and patients stopping solifenacin should have a 3 week period between Screening (Visit 1) and Week-2 (Visit 2). (c) Subjects who may be antimuscarinic treatment resistant: previously treated with three or more antimuscarinic OAB medications within 12 months prior to Screening, which may include darifenacin, fesoterodine, oxybutynin, propiverine, solifenacin, tolterodine or trospium. (d) Has started treatment with tricyclic antidepressants or estrogens within 4 weeks and/or is not on a stable dose. (e) Has started treatment with diuretics, alpha blockers or 5-alpha reductase inhibitors within 2 weeks and/or is not on a stable dose. (f) Hepatic Metabolism influencers with potential for drug-drug interaction: (i) Treatment with potent CYP3A4 inhibitors such as clarithromycin, ketoconazole and itraconazole within 2 weeks prior to Visit 1 (ii) Administration of medications capable of inducing hepatic enzyme metabolism or transport (eg, barbiturates, rifampicin, carbamazepine, phenytoin, primidone, or St. John’s Wort) in the past 30 days. Subjects should be advised to continue on established stable doses of concomitant medications when necessary and maintain their regimen at a stable dose through the course of the study. 7. Participation in other studies within 30 days prior to study entry. 8. Alcohol abuse or misuse and/or any other drug/substance abuse or misuse within 2 years in opinion of investigator. 9. Subjects who have any medical (including known history of major hematological, renal, cardiovascular 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. |
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| 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 (Visit 5) relative to Week 0 (Visit 3), defined as those micturitions with Urinary Sensation Scale rating of 5 in the diary. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Week 12 (visit 5) compared to Week 0 (visit 3) |
|
| E.5.2 | Secondary end point(s) |
Efficacy - Change in mean number of micturitions (frequency) per 24 hours at Week 12 (Visit 5) relative to Week 0 (Visit 3); Change in mean number of micturition-related urgency episodes per 24 hours at Week 12 (Visit 5) relative to Week 0 (Visit 3), defined as those micturitions with Urinary Sensation Scale rating of ≥3 in the bladder diary; Change in Patient Perception of Bladder Condition (PPBC) at Week 12 (Visit 5) relative to Week 0 (Visit 3); Change in Urgency Perception Scale (UPS) at Week 12 (Visit 5) relative to Week 0; Change in Overactive Bladder Questionnaire (OAB-q) symptom bother score and change in the Total Health-Related Quality of Life (HRQL) score of the OAB-q and score of each HRQL domain of the OAB-q at Week 12 (Visit 5) relative to Week 0 (Visit 3); Responder rates from Week -2 (Visit 2) to Week 12 (Visit 5) and from Week 0 (Visit 3) to Week 12 (Visit 5), defined as a >50% reduction in UUI episode frequency; Diary dry rate at Week 4 (Visit 4) and Week 12 (EOT).
Safety and tolerability: Adverse events; Vital Signs; Urinalysis and urine culture at Screening (Visit 1), Week -2 (Visit 2) and Week 12, (Visit 5). |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Week 12 (visit 5) compared to Week 0 (visit 3) |
|
| 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 | No |
| 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.6.13.1 | Other scope of the trial description |
|
| 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 | Yes |
| E.8.1.7.1 | Other trial design description |
| 2 week open label tolterodine run-in |
|
| 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.8.2.4 | Number of treatment arms in the trial | 1 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
| 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 | 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 | 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 |
| Brazil |
| Bulgaria |
| Colombia |
| Czech Republic |
| Egypt |
| Finland |
| France |
| Germany |
| Greece |
| Hungary |
| India |
| Italy |
| Korea, Republic of |
| Lithuania |
| Mexico |
| Poland |
| Russian Federation |
| South Africa |
| Spain |
| Sweden |
| Turkey |
| Ukraine |
| United Kingdom |
|
| 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
|
|
| 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 | 22 |
| 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 | 22 |
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