A Study to Compare the Effectiveness and Safety of Fesoterodine and Placebo in an Elderly Population of Patients Who go to the Toilet Very Frequently Due to Overactive Bladder.

Study Overview
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Brief Summary
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The drug being studied, fesoterodine fumarate helps prevent the bladder neck opening at unwanted times and has been shown to help patients with overactive bladder syndrome pass urine less frequently than before treatment. It is postulated that this drug will also prove effective in elderly patients (aged > 65 years) and that the ability to change dose between 4 and 8mg will allow each patient to have an optimised treatment.

Official Title
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A 24-Week, Multi-Centre Trial, Comprising A 12-Week, Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Phase Followed By A 12-Week Open-Label Phase, To Evaluate The Efficacy And Safety Of A Fesoterodine Flexible Dose Regimen In Elderly Patients With Overactive Bladder.

Conditions
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Urinary Bladder, Overactive

Intervention / Treatment
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* Drug: Placebo
* Drug: Fesoterodine fumarate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥65 years old. Overactive bladder symptoms for at least 3 months prior to study start. Eight or more micturitions per 24 hours as confirmed by diary records Exclusion Criteria: Predominant Stress Urinary Incontinence Active or recurrent bladder infections Other bladder and genital conditions that could be the predominant cause of symptoms or interfere with treatment assessment and success.

Ages Eligible for Study
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Minimum Age: 65 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Placebo<br>Flexible dose regimen of placebo once daily. The dose can be increased after 4 weeks if clinically indicated. Subsequently the dose can be reduced to the original dose if clinically indicated. | Drug: Placebo<br>* placebo administered orally in the morning or evening.<br>|
| Active Comparator: Fesoterodine<br>Flexible dose regimen of fesoterodine fumarate 4mg once daily. The dose can be increased to 8mg once daily after 4 weeks if clinically indicated. Subsequently the dose can be reduced to 4mg if clinically indicated. | Drug: Fesoterodine fumarate<br>* Fesoterodine fumarate is an antimuscarinic drug recently approved by the European Medicines Evaluation Agency for treatment of symptoms of overactive bladder syndrome.<br>* Other names: Toviaz;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Number of Micturition-Related Urgency Episodes Per 24 Hours at Week 12 | Number of micturition-related urgency episodes per 24 hours calculated as number of micturitions with USS rating of greater than or equal to (>=) 3 divided by number of days that diary data was collected at that visit. USS ranged 1 to 5 (1. No feeling of urgency, 2. Mild feeling of urgency, 3. Moderate feeling of urgency, 4. Severe feeling of urgency, 5. Unable to hold; leak urine). Change = observation minus baseline, where lower scores were an improvement/decrease in micturition-related urgency episodes. | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Micturition-Related Urgency Episodes Per 24 Hours at Weeks 4, 8, and 12 | Micturition-related urgency episodes per 24 hours defined as those with USS Scale rating of >=3 marked for corresponding micturition in diary. USS rating of 3: Moderate feeling of urgency, 4: Severe feeling of urgency, 5: Unable to hold; leak urine. Percent change calculated as: 100* (Urgency Episode at Week x - baseline)/baseline. Change = observation minus baseline, where lower scores were an improvement/decrease in micturition-related urgency episodes. | Baseline and Weeks 4, 8, and 12 | 
| Change From Baseline in Mean Number of Severe Micturition-Related Urgency Episodes Per 24 Hours at Weeks 4, 8, and 12 | Severe micturition-related urgency episodes defined as those with the USS rating >=4. USS rating of 4: Severe feeling of urgency and 5: Unable to hold; leak urine. Change = observation minus baseline, where lower scores were an improvement/decrease in severity of micturition-related urgency episodes. | Baseline and Weeks 4, 8, and 12 | 
| Percent Change From Baseline of Severe Micturition-Related Urgency Episodes Per 24 Hours at Weeks 4, 8, and 12 | Severe micturition-related urgency episodes defined as those with USS rating >=4. USS rating of 4: Severe feeling of urgency and 5: Unable to hold; leak urine. Change = observation minus baseline, where lower scores were an improvement/decrease in severity of micturition-related urgency. | Baseline and Weeks 4, 8, and 12 | 
| Change From Baseline in Mean Number of Micturitions Per 24 Hours at Weeks 4, 8, and 12 | Micturitions included episodes of voluntary micturition and episodes of UUI, defined as those micturitions with USS rating of 5 (unable to hold; leak urine) in the diary of participants with UUI at baseline. Change = observation minus baseline, where lower scores were an improvement/decrease in micturitions. | Baseline and Weeks 4, 8, and 12 | 
| Percent Change From Baseline in Micturitions Per 24 Hours at Weeks 4, 8, and 12 | Micturitions included episodes of voluntary micturition and episodes of UUI. Change = observation minus baseline, where lower scores were an improvement/decrease in micturitions. | Baseline and Weeks 4, 8, and 12 | 
| Change From Baseline in Number of Nocturnal Micturitions Per 24 Hours at Weeks 4, 8, and 12 | Nocturnal micturitions defined as micturitions with USS rating 1-5 that occurred between time participant went to bed and time he or she arose to start the next day. USS rating: 1. No feeling of urgency, 2. Mild feeling of urgency, 3. Moderate feeling of urgency, 4. Severe feeling of urgency, 5. Unable to hold; leak urine. Calculated as number of nocturnal micturitions divided by number of diary days collected at that visit. Change = observation minus baseline, where lower scores were an improvement/decrease in nocturnal micturitions. | Baseline and Weeks 4, 8, and 12 | 
| Percent Change From Baseline in Nocturnal Micturitions Per 24 Hours at Weeks 4, 8, and 12 | Nocturnal micturitions defined as micturitions with USS rating 1-5 that occurred between time participant went to bed and time he or she arose to start the next day. USS rating: 1. No feeling of urgency, 2. Mild feeling of urgency, 3. Moderate feeling of urgency, 4. Severe feeling of urgency, 5. Unable to hold; leak urine. Change = observation minus baseline, where lower scores were an improvement/decrease in nocturnal micturitions. | Baseline and Weeks 4, 8, and 12 | 
| Change From Baseline in Number of Urgency Urinary Incontinence (UUI) Episodes Per 24 Hours at Weeks 4, 8, and 12 | UUI episodes defined as those with USS rating of 5 (unable to hold; leak urine) in the diary. Change = observation minus baseline, where lower scores were an improvement/decrease in UUI episodes. | Baseline and Weeks 4, 8, and 12 | 
| Percent Change From Baseline of UUI Episodes Per 24 Hours at Weeks 4, 8, and 12 | UUI episodes defined as those with the USS rating of 5 (unable to hold; leak urine)in the diary. Change = observation minus baseline, where lower scores were an improvement/decrease in UUI episodes. | Baseline and Weeks 4, 8, and 12 | 
| Change From Baseline in Daily Sum Rating in USS at Weeks 4, 8, and 12 | USS total range 1 to 5 (1. No feeling of urgency, 2. Mild feeling of urgency, 3. Moderate feeling of urgency, 4. Severe feeling of urgency, 5. Unable to hold; leak urine). Change = observation minus baseline, where lower scores were an improvement/decrease in urinary sensation. | Baseline and Weeks 4, 8, and 12 | 
| Percentage of Participants Who Were Incontinent at Baseline and Became Dry | Percentage of participants who had at least 1 UUI episode during baseline period and were dry (no UUI episodes) in the 3 days prior to study visits at week 8 and 12. UUI episodes defined as those with USS rating of 5 (unable to hold; leak urine) in the diary. | Weeks 8 to 12 | 
| Change From Baseline in Number of Skin Protective Agents Used by Participants at Weeks 4, 8, and 12 | Skin protective agents included incontinence pads, barrier creams, and powders. Change = observation minus baseline, where lower scores were an improvement/decrease in protective skin agents used. | Baseline and Weeks 4, 8, and 12 | 
| Percentage of Participants With Improvement at Week 12 | Patient Treatment Benefit Scale (PTBS): single-item scale assessed fesoterodine efficacy and safety in participants with overactive bladder. Participants asked to compare their present condition with their condition before start of trial: My condition has been: 1=Greatly Improved; 2=Improved; 3=Not Changed; 4=Worsened, During Treatment. Improvement was defined as a rating of 1 or 2. | Week 12 | 
| Change From Baseline in Patient Perception of Bladder Condition (PPBC) at Week 4 | PPBC: self-administered, single-item, questionnaire that asked participants to describe their perception of their bladder-related problems. PPBC assessment rated on a 6-point scale: 1=no problems at all, 2=some very minor problems, 3=some minor problems, 4=moderate problems, 5=severe problems, 6=many severe problems. Change = observation minus baseline. Results categorized as Deterioration (score difference ≥1), No Change (score difference=0), Improvement (score difference less than [<]0). | Baseline and Week 4 | 
| Change From Baseline in PPBC at Week 8 | PPBC: self-administered, single-item, questionnaire that asked participants to describe their perception of their bladder-related problems. PPBC assessment rated on a 6-point scale: 1=no problems at all, 2=some very minor problems, 3=some minor problems, 4=moderate problems, 5=severe problems, 6=many severe problems. Change = observation minus baseline. Results categorized as Deterioration (score difference ≥1), No Change (score difference=0), Improvement (score difference <0). | Baseline and Week 8 | 
| Change From Baseline in PPBC at Week 12 | PPBC: self-administered, single-item, questionnaire that asked participants to describe their perception of their bladder-related problems. PPBC assessment rated on a 6-point scale: 1=no problems at all, 2=some very minor problems, 3=some minor problems, 4=moderate problems, 5=severe problems, 6=many severe problems. Change = observation minus baseline. Results categorized as Deterioration (score difference ≥1), No Change (score difference=0), Improvement (score difference <0). | Baseline and Week 12 | 
| Change From Baseline in PPBC at Week 24 | PPBC: self-administered, single-item, questionnaire that asked participants to describe their perception of their bladder-related problems. PPBC assessment rated on a 6-point scale: 1=no problems at all, 2=some very minor problems, 3=some minor problems, 4=moderate problems, 5=severe problems, 6=many severe problems. Change = observation minus baseline. Results categorized as Deterioration (score difference ≥1), No Change (score difference=0), Improvement (score difference <0). | Baseline and Week 24 | 
| Change From Baseline Patient Perception of Urgency Scale (PPUS) at Week 4 | PPUS: self-administered, single-item, questionnaire that measured the participant's perception of urinary urgency. It was sensitive to changes in perceptions of urinary urgency over time. Scale of 0 (usually not able to hold urine), 1 (usually able to hold urine [without leaking] until reaching toilet if go to toilet immediately), or 2 (usually able to finish what he/she was doing before going to toilet [without leaking]). Change = observation minus baseline. Improvement in PPUS defined as increase of 1 or more points in difference of scores relative to baseline. | Baseline and Weeks 4 | 
| Change From Baseline in PPUS at Week 8 | PPUS: self-administered, single-item, questionnaire that measured the participant's perception of urinary urgency. It was sensitive to changes in perceptions of urinary urgency over time. Scale of 0 (usually not able to hold urine), 1 (usually able to hold urine [without leaking] until reaching toilet if go to toilet immediately), or 2 (usually able to finish what he/she was doing before going to toilet [without leaking]). Change = observation minus baseline. Improvement in PPUS defined as increase of 1 or more points in difference of scores relative to baseline. | Baseline and Week 8 | 
| Change From Baseline in PPUS at Week 12 | PPUS: self-administered, single-item, questionnaire that measured the participant's perception of urinary urgency. It was sensitive to changes in perceptions of urinary urgency over time. Scale of 0 (usually not able to hold urine), 1 (usually able to hold urine [without leaking] until reaching toilet if go to toilet immediately), or 2 (usually able to finish what he/she was doing before going to toilet [without leaking]). Change = observation minus baseline. Improvement in PPUS defined as increase of 1 or more points in difference of scores relative to baseline. | Baseline and Week 12 | 
| Change From Baseline in PPUS at Week 24 | PPUS: self-administered, single-item, questionnaire that measured the participant's perception of urinary urgency. It was sensitive to changes in perceptions of urinary urgency over time. Scale of 0 (usually not able to hold urine), 1 (usually able to hold urine [without leaking] until reaching toilet if go to toilet immediately), or 2 (usually able to finish what he/she was doing before going to toilet [without leaking]). Change = observation minus baseline. Improvement in PPUS defined as increase of 1 or more points in difference of scores relative to baseline. | Baseline and Week 24 | 
| Change From Baseline in Overactive Bladder Satisfaction Questionnaire (OAB-q) Symptom/Bother Score at Weeks 4, 8, 12, and 24 | OAB-q: self-administered, 33-item, questionnaire assessed how much participant was bothered by selected bladder symptoms during previous week. Each item rated by participant on Likert scale 1 (least symptom bother) to 6 (most symptom bother). Raw scores transformed to a score from 0-100 where higher scores represented less favorable outcome. Change = baseline minus observation and higher scores were an improvement. | Baseline and Weeks 4, 8, 12, and 24 | 
| Change From Baseline in Overactive Bladder Satisfaction Questionnaire (OAB-q) Total Score at Weeks 4, 8, 12, and 24 | OAB-q: self-administered, 33-item, questionnaire assessed how much participant was bothered by selected bladder symptoms during previous week. Each item rated by participant on Likert scale 1 (least symptom bother) to 6 (most symptom bother). Raw scores transformed to a score from 0-100 where higher scores represented less favorable outcome. Change = observation minus baseline and higher scores were an improvement. | Baseline and Weeks 4, 8, 12, and 24 | 
| Change From Baseline in OAB-q Subscale Scores at Weeks 4, 8, 12, and 24 | OAB-q: self-administered, 33-item, questionnaire assessed how much participant bothered by bladder symptoms during previous week. Each item rated by participant on Likert scale 1 (least symptom bother) to 6 (most symptom bother). Raw scores transformed to 0-100 score where higher scores were less favorable outcome. Questions 1-8 constituted symptom severity/bother score. Questions 9-33 constitute HRQL component, which included domains of coping, concern, sleep, and social function. Change = observation minus baseline and higher scores were an improvement. | Baseline and Weeks 4, 8, 12, and 24 | 
| Change From Week 12 in Overactive Bladder Satisfaction (OAB-S) Scale for Satisfaction With OAB Control at Week 24 | OAB-S: validated self-administered instrument that evaluated OAB medication expectations, daily life with OAB, and satisfaction with OAB medication and included 3 stand-alone items that assessed overall expectation, satisfaction, and willingness to continue treatment. Satisfaction coded on scale of 1-5: (1-very satisfied to 5-very dissatisfied). Coding reversed algorithmically and results transformed: total score range 0-100. Higher final response value associated with better satisfaction. Change = score at Week 24 minus score at Week 12 where higher scores indicated better satisfaction. | Weeks 12 and 24 | 
| Change From Week 12 in OAB-S Scale for OAB Medication Expectation at Week 24 | OAB-S: evaluated OAB medication expectations, daily life with OAB, and satisfaction with OAB medication. Included 3 stand-alone items that assessed overall expectation, satisfaction, and willingness to continue treatment. Medication expectation coded on scale 1=Greatly exceeds my expectations to 5=Does not meet my expectations at all. Coding reversed by subtracting initial response value from 6, so higher final response value associated with better fulfilment of OAB medication expectations. | Weeks 12 and 24 | 
| Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores at Week 12 | KHQ: self-administered questionnaire contained 21 questions scored in 9 domains (general health perception, incontinence impact, role limitations, physical limitations, social limitations, personal relationships, emotions, sleep/energy, severity of urinary symptoms). Range: 0-100, where 0=best outcome/response and 100=worst outcome/response. Change = observation minus baseline, where lower scores indicated better outcome/response. | Baseline and Week 12 | 
| Change From Baseline in EQ-5D- Health State Profile Utility Score at Week 12 | EQ-5D: participant rated questionnaire to assess HRQL in terms of single index value. Visual Analogue Scale (VAS) component rated current health state on scale from 0 (worst imaginable health state) to 100 (best imaginable health state). For each question, scores categorized into 3 levels of response, level 1=no health problems, 2=some problems and 3= extreme problems, and health state profile utility score derived from these, which could range from 1 prefect health to -0.594 worst possible health. Change = observation minus baseline, where higher scores indicated a better health state. | Baseline and Week 12 | 
| Change From Baseline in EQ-5D- Each Dimension Score at Week 12 | EQ-5D: participant rated questionnaire to assess HRQL in terms of a single utility score. Health State Profile component assessed level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicated better health state; 3 indicated worst health state. Scoring formula assigned utility value for each domain in profile. Score was transformed and results in total score could have ranged from -0.594 to 1.000; Change = observation minus baseline, where higher scores indicated a better health state. | Baseline and Week 12 | 
| Change From Baseline in Mini Mental State Examination (MMSE) at Week 12 | MMSE measured general cognitive functioning: orientation, memory, attention, calculation, language, visuospatial functions. Total score derived from sub-scores; total ranged from 0 - 30, higher score indicated better cognitive state. Change = observation minus baseline where higher scores indicated better cognitive functioning. | Baseline and Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Overactive bladder syndrome, fesoterodine, elderly, flexible dose regimen, urgency, frequency, urge urinary incontinence, anticholinergic, antimuscarinic