Clinical Trial to Evaluate the Efficacy and Safety of Fesoterodine in Comparison to Tolterodine Extended Release(ER)in Patients With Overactive Bladder.

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of fesoterodine in comparison to tolterodine and placebo for overactive bladder

Official Title
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12-Week, Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Parallel-Group, Multicenter Trial To Evaluate The Efficacy And Safety Of Fesoterodine In Comparison To Tolterodine ER In Patients With Overactive Bladder.

Conditions
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Overactive Bladder

Intervention / Treatment
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* Drug: Tolterodine ER
* Drug: Placebo
* Drug: Fesoterodine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult subjects with overactive bladder symptoms (subject-reported) for greater than or equal to 3 months prior to Screening/Enrollment visit. Reported at least an average of 1 UUI episode per 24 hours in the 3-day bladder diary prior to the Randomization/Baseline visit Mean urinary frequency of greater than or equal to 8 micturitions per 24 hours as verified by the 3-day bladder diary prior to randomization/Baseline visit. Exclusion Criteria: Subjects with 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. Subjects with clinically significant hepatic or renal disease or other significant unstable diseases. OAB symptoms caused by neurological conditions, known pathologies of urinary tract, etc. Subjects with previous history of acute urinary retention requiring catheterization, or severe voiding difficulties in the judgment of the investigator, prior to baseline.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br> | Drug: Tolterodine ER<br>* The tolterodine treatment will be 4 mg once daily(QD) for 12 weeks.<br>|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* Placebo treatment will be once daily(QD) for 12 weeks.<br>|
| Experimental: 3<br> | Drug: Fesoterodine<br>* The fesoterodine treatment will start with 4 mg once daily(QD) for 1 week followed by a forced dose-escalation to 8mg once daily(QD) for 11 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Number of Urgency Urinary Incontinence (UUI) Episodes Per 24 Hours at Week 12 | UUI per 24 hours: total number of micturitions with Urinary Sensation Scale (USS) of 5 divided by total number of diary days collected at visit. USS: 5-item scale to measure urinary urgency; range: 1 (no feeling of urgency) to 5 (unable to hold; leak urine). | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Voided Volume Per Micturition | Mean voided volume in milliliters (mL) calculated as sum of voided volume divided by the total number of micturition episodes with a recorded voided volume greater than 0 in the 3-day diary at that visit. | Baseline, Week 1, Week 4, Week 12 | 
| Change From Baseline in Mean Number of Micturitions Per 24 Hours | The mean number of micturitions was calculated as the total number of micturitions divided by the total number of diary days collected at that visit. | Baseline, Week 1, Week 4, Week 12 | 
| Percent Change From Baseline of Micturitions Per 24 Hours | Percent change of micturitions per 24 hours was calculated as change in 24-hour mean at that visit divided by the baseline 24-hour mean multiplied by 100 (ie, 100%*(Week 1 or 4 or 12 - baseline)/baseline). | Baseline, Week 1, Week 4, Week 12 | 
| Change From Baseline in Mean Number of Nocturnal Micturitions Per 24 Hours | Mean number of nocturnal micturitions per 24 hours was calculated as the total number of all micturitions divided by the total number of diary days collected at that visit. Nocturnal micturitions are those recorded in the Bedtime section of the diary. Nocturnal (Bedtime) was defined as the time the participant went to bed until he/she arose to start the next day. | Baseline, Week 1, Week 4, Week 12 | 
| Percent Change From Baseline of Nocturnal Micturitions Per 24 Hours | Percent change of nocturnal micturitions per 24 hours was calculated as change in 24-hour mean at that visit divided by the baseline 24-hour mean multiplied by 100 (ie, 100%*(Week 1 or 4 or 12 - baseline)/baseline). Nocturnal micturitions are those recorded in the Bedtime section of the diary. Nocturnal (Bedtime) was defined as the time the participant went to bed until he/she arose to start the next day. | Baseline, Week 1, Week 4, Week 12 | 
| Change From Baseline in Mean Number of Urgency Urinary Incontinence (UUI) Episodes Per 24 Hours at Week 1 and Week 4 | UUI episodes per 24 hours calculated as total number of micturitions with Urinary Sensation Scale (USS) of 5 divided by total number of diary days collected at visit. USS is 5-item scale measuring urinary urgency; range is 1 (no feeling of urgency) to 5 (unable to hold; leak urine). | Baseline, Week 1, Week 4 | 
| Percent Change From Baseline of UUI Episodes Per 24 Hours | UUI episodes per 24 hours calculated as total number of micturitions with USS of 5 in diary. USS is 5-item scale measuring urinary urgency; range is 1 (no feeling of urgency) to 5 (unable to hold; leak urine). Change calculated as UUI episodes per 24 hours at observation divided by baseline number of UUI episodes per 24 hours, multiplied by 100. | Baseline, Week 1, Week 4, Week 12 | 
| Change From Baseline in Mean Number of Urgency Urinary Episodes Per 24 Hours (Urinary Sensation Scale ≥3 in the Diary) | Urgency Urinary episodes per 24 hours: total number of micturitions with Urinary Sensation Scale (USS) of ≥3 divided by total number of diary days collected at visit. USS: 5-item scale to measure urinary urgency; range: 1 (no feeling of urgency) to 5 (unable to hold; leak urine). | Baseline, Week 1, Week 4, Week 12 | 
| Percent Change From Baseline in Mean Number of Urgency Urinary Episodes Per 24 Hours (Urinary Sensation Scale ≥3 in the Diary) | Percent change from baseline in mean number of Urgency Urinary episodes per 24 hours (Urinary Sensation Scale ≥3 in the diary). Change calculated as UUI episodes per 24 hours at observation divided by baseline number of UUI episodes per 24 hours, multiplied by 100. | Baseline, Week 1, Week 4, Week 12 | 
| Change From Baseline in Mean Number of Severe Urgency Episodes Per 24 Hours | Mean number of severe urgency episodes (USS rating ≥4 in diary ) per 24 hours calculated as the total number of micturitions with USS ≥4 divided by total number of diary days collected at that visit. USS: 5-item scale to measure urinary urgency; range: 1 (no feeling of urgency) to 5 (unable to hold; leak urine). | Baseline, Week 1, Week 4, Week 12 | 
| Percent Change From Baseline of Severe Urgency Episodes Per 24 Hours | Percent change calculated as change in severe urgency episodes (USS rating ≥4 in diary ) per 24 hours at that visit divided by the baseline number of severe urgency episodes per 24 hours, multiplied by 100. USS is 5-item scale measuring urinary urgency; range is 1 (no feeling of urgency) to 5 (unable to hold; leak urine). | Baseline, Week 1, Week 4, Week 12 | 
| Change From Baseline in Mean Urinary Sensation Scale (USS) Rating Per Micturition Per 24 Hours. | Mean USS rating calculated as the sum of rating scores on USS per 24 hours divided by the total number of micturitions per 24 hours with non-missing rating at that visit. USS is 5-item scale measuring urinary urgency; range is 1 (no feeling of urgency) to 5 (unable to hold; leak urine). | Baseline, Week 1, Week 4, Week 12 | 
| Change From Baseline in Frequency-Urgency Sum (FUS) Per 24 Hours (Synonymous With USS Sum in the Study Protocol) | Frequency-Urgency Sum per 24 hours calculated as mean rating scores on the USS multiplied by the mean number of micturitions per 24 hours at that visit. USS is 5-item scale measuring urinary urgency; range is 1 (no feeling of urgency) to 5 (unable to hold; leak urine). | Baseline, Week 1, Week 4, Week 12 | 
| Diary Dry Rate: Percentage of Participants With no Urgency Urinary Incontinence (UUI) in the 3-day Bladder Diary | Diary dry rate: percentage of participants with no urgency urinary incontinence episode reported in the 3 day diary at the respective time-point; based on USS: 5-item scale measuring urinary urgency; range is 1 (no feeling of urgency) to 5 (unable to hold; leak urine). | Week 1, Week 4, Week 12 | 
| Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Number of participants in 4-point category: ≥2 points improvement (major improvement; negative change from baseline); 1 point improvement (minor improvement); no change; deterioration (positive change from baseline), based on PPBC score (rated on 6-point scale: 1=no problems at all; 6=many severe problems). Score change: score at observation minus score at baseline; re-scaled to 4-point categorical variables. | Baseline, Week 1, Week, 4, Week 12 | 
| Change From Baseline in Urgency Perception Scale (UPS). UPS Formerly Known as Patient Perception of Urgency Scale (PPUS) in the Protocol. | Number of participants in 3-point category: improvement [≥1-point improvement]; no change; deterioration [≥1-point decrease], based on UPS score (rated on 3-point scale: 1=not able to hold urine; 3=able to finish what I am doing). Score change calculated as score at observation minus score at baseline; re-scaled to 3-point categorical variables. | Baseline, Week 1, Week, 4, Week 12 | 
| Change From Baseline in Overactive Bladder Questionnaire (OAB-q): Symptom Bother Score at Week 12 | Symptom bother score derived as sum of scores for questions 1-8; lowest possible raw score: 8; highest possible score: 48. Data analyzed based on transformation of the score to a 0 to 100 scale [(Actual total raw score - lowest possible value of raw score)/range]*100. Higher scores values indicative of greater symptom bother. Negative change in Symptom Bother Score indicates improvement. | Baseline, Week 12 | 
| Change From Baseline in Overactive Bladder Questionnaire (OAB-q): Health Related Quality of Life (HRQL) at Week 12 | HRQL domain and total raw score derived as sum of scores (6-point scale: 1=not at all/none of the time; 6=a very great deal/all of the time). Transformed score (Total HRQL or domain)=[(Highest possible raw score- Actual total raw score)/Raw score range] * 100. Higher transformed scores indicative of better HRQL. Positive change in HRQL Score indicates improvement. | Baseline, Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment of overactive bladder