E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 14.0 |
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 |
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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 demonstrate the greater efficacy of 8 mg of fesoterodine compared to 4 mg fesoterodine in reducing UUI in subjects with OAB after 12 weeks of treatment. |
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E.2.2 | Secondary objectives of the trial |
To determine the efficacy of 8 mg fesoterodine and 4 mg fesoterodine on diary endpoints after 4 and 12 weeks of treatment and patient reported outcomes (PRO) after 12 weeks of treatment in subjects with OAB.
To determine the efficacy of 8 mg fesoterodine and 4 mg fesoterodine compared to placebo on diary endpoints after 4 and 12 weeks of treatment and patient reported outcomes (PRO) after 12 weeks of treatment in subjects with OAB.
To summarize safety and tolerability data for 12 weeks of treatment with fesoterodine 8 mg and 4 mg and placebo in subjects with OAB. |
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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 V1
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 must not be pregnant, nursing, or have a positive urine pregnancy test or be intending to become pregnant within 3 months after the completion of the trial. Female subjects of childbearing potential 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), contraceptive pills of combination type, 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 trial-related activities.
In addition at V2
7. Mean urinary frequency of ≥8 micturitions per 24 hours as verified by 3-day bladder
diary prior to Visit 2.
8. Mean of between ≥2 UUI and ≤ 15 UUI episodes per day as verified by 3-day bladder diary prior to Visit 2 [defined as those micturitions with Urinary Sensation Scale rating of 5 in the diary]. |
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E.4 | Principal exclusion criteria |
1. Subjects who are investigational site staff members or subjects who are Pfizer employees directly involved in the conduct of the trial.
2. Any condition that would contraindicate their use of fesoterodine including:
hypersensitivity to 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.
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 the
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 incontinence being predominately stress urinary incontinence as
determined by the 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 an indwelling catheter or an intermittent
self-catheterization program, urodynamic evidence of obstruction or severe voiding
symptoms including a previously measured post-void residual volume of > 200 ml
which has not subsequently been appropriately managed.
4. Clinically significant urinary tract infection (UTI) as shown by the results of the
urinalysis at Screening or Randomization or recurrent urinary tract infection (RUTIs)
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 the event of symptoms (eg, fever, dysuria), or positive leucocytes, nitrites and/or protein on urinalysis. Re-screening may be performed when the UTI has been treated and urine is culture negative, assuming the subject does not meet the definition for recurrent UTI.
5. Initiation of: electrostimulation, 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; subjects who are already established on stable therapy should continue with their regimen at a stable level through the course of the study.
6. Treatment with the following drugs as specified below:
a. Treatment with intra-vesical Botulinum toxin within 6 months of Visit 1.
b. Any other drugs with significant anticholinergic and antispasmodic effects (these
must be discontinued for a minimum of 2 weeks prior to Visit 1 except solifenacin
which should be discontinued for a minimum of 3 weeks prior to Visit 1).
c. Has started treatment with tricyclic antidepressants or estrogens within 4 weeks of Visit 1 and/or is not on a stable dose.
d. Has started treatment with diuretics, alpha blockers or 5 alpha reductase inhibitors within 2 weeks of Visit 1 and/or is not on a stable dose.
e. 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 30 days prior to Visit 1. NB. Subjects should endeavor to continue on established stable doses of concomitant medications, and if possible maintain their regimen at a stable dose through the course of the study.
7. Participation in other studies within 30 days prior to Visit 1 and/or during study
participation.
8. Alcohol abuse or misuse and/or any other drug/substance abuse or misuse within 2 years in the opinion of the 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 trial or may
interfere with the interpretation of study results, 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 relative to baseline (defined as those micturitions with Urinary Sensation Scale rating of 5 in the diary). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Change in mean number of micturitions (frequency) per 24 hours at Weeks 4 and 12
relative to baseline;
Percent change of micturitions per 24 hours at Weeks 4 and 12 relative to baseline;
Change in mean number of urgency urinary incontinence (UUI) episodes per 24 hours at
Week 4 relative to baseline (UUI episodes are defined as those micturitions with Urinary
Sensation Scale rating of 5 in the diary);
Percent change of urgency urinary incontinence (UUI) episodes per 24 hours at Week 4 and 12 relative to baseline (UUI episodes are defined as those micturitions with Urinary Sensation Scale rating of 5 in the diary);
Change in mean number of micturition-related urgency episodes per 24 hours at Weeks 4 and 12 relative to baseline (Micturition-related urgency episodes are defined as those
micturitions with Urinary Sensation Scale rating of ≥3 in the diary);
Percent change of micturition-related urgency episodes per 24 hours at Weeks 4 and 12
relative to baseline (Micturition-related urgency episodes are defined as those micturitions with Urinary Sensation Scale rating of ≥3 in the diary);
Change in Patient Perception of Bladder Condition (PPBC) at Week 12 relative to
baseline.
Change in Urgency Perception Scale (UPS) at Week 12 relative to baseline.
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 relative to baseline.
Diary dry rate at Weeks 4 and 12 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. 4 & 12 weeks
2. 4 & 12 weeks
3. 4 weeks
4. 4 & 12 weeks
5. 4 & 12 weeks
6. 4 & 12 weeks
7. 12 weeks
8. 12 weeks
9. 12 weeks
10. 4 & 12 weeks |
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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 | 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 | 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.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 140 |
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 |
Austria |
Bulgaria |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Greece |
Hungary |
Italy |
Lithuania |
Norway |
Poland |
Slovakia |
Spain |
Sweden |
Ukraine |
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 | 3 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 3 |