Clinical Trial to Evaluate the Efficacy and Safety of Fesoterodine in Comparison to Tolterodine for Overactive Bladder (OAB)

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 (OAB)

Conditions
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Overactive Bladder

Intervention / Treatment
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* Drug: fesoterodine fumarate
* Drug: placebo
* Drug: tolterodine tartrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult overactive bladder (OAB) patients who present with OAB symptoms, including urinary frequency >= 8 per day and urgency urinary incontinence >=1 per day Exclusion Criteria: Patients with conditions that would contraindicate for fesoterodine use, e.g, hypersensitivity to the active substance (fesoterodine) or to peanut or soya or any of the excipients, urinary retention, and gastric retention. Patients with significant hepatic and renal disease or other significant unstable diseases. OAB symptoms caused by neurological conditions, known pathologies of urinary tract, etc.

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 |
| --- | --- |
| Experimental: Fesoterodine<br>Tablets | Drug: fesoterodine fumarate<br>* 4 mg once daily (OD) for 1 week followed by a forced dose-escalation to 8 mg once daily (OD) for 11 weeks<br>|
| Placebo Comparator: Placebo<br>Tablets and capsules | Drug: placebo<br>* once daily (OD)for 12 weeks<br>|
| Active Comparator: Tolterodine<br>Capsules | Drug: tolterodine tartrate<br>* 4 mg once daily (OD) for 12 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 (End of Treatment). | 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). Change: mean at observation minus mean at baseline. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Number of 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). Change calculated as mean at observation minus mean at baseline. | 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 Voided Volume Per Micturition. | Mean voided volume 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 sum of all micturitions divided by the total number of diary days collected at that visit. Change calculated as mean at observation minus mean at baseline. | 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 12 or 4 - 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 sum of all micturitions divided by the total number of diary days collected at that visit. Nocturnal (Bedtime) was defined as the time the subject 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 12 or 4 - baseline)/baseline). Nocturnal (Bedtime) was defined as the time the subject 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 Episodes Per 24 Hours. | Mean number urgency episodes (USS rating >= to 3 in diary) per 24 hours calculated as sum of all micturitions divided by total number of diary days collected at visit. USS: 5-item scale measuring urinary urgency; range is 1 (no feeling of urgency) to 5 (unable to hold; leak urine). Change calculated as mean at observation minus mean at baseline. | Baseline, Week 1, Week 4, Week 12 | 
| Percent Change From Baseline of Urgency Episodes Per 24 Hours. | Percent change of urgency episodes (USS rating >= to 3 in diary) per 24 hours calculated as change in 24-hour mean at that visit divided by the baseline 24-hour mean multiplied by 100. USS: 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 Number of Severe Urgency Episodes Per 24 Hours. | Mean number of severe urgency episodes (USS rating >= to 4 in diary ) per 24 hours: sum of all micturitions 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). Change calculated as mean at observation minus mean at baseline. | 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 >= to 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 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 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). Change calculated as mean at observation minus mean at baseline. | Baseline, Week 1, Week 4, Week 12 | 
| Change From Baseline in Frequency-Urgency Sum (Formerly Known as Urinary Sensations Scale Sum in Protocol) Per 24 Hours. | Frequency-Urgency Sum rating 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). Change calculated as mean at observation minus mean at baseline. | Baseline, Week 1, Week 4, Week 12 | 
| Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Number of subjects in 4-point category: >= to 2 points improvement [major improvement]; 1 point improvement [minor improvement]; no change; deterioration, 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 Equals Patient Perception of Urgency Scale (PPUS) in Protocol. | Number of subjects 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 (End of Treatment). | 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)/by raw score range * 100]. Higher transformed scores indicative of greater symptom bother. Negative change in Symptom Bother score indicates improvement. Change calculated as score at observation minus score at baseline. | Baseline, Week 12 | 
| Change From Baseline in OAB-q: Health Related Quality of Life (HRQL) at Week 12 (End of Treatment). | 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]x100. Higher transformed scores indicative of better HRQL. Positive change in HRQL scores indicates improvement. Change: score at observation minus score at baseline. | Baseline, Week 12 |