Web-based Methodology Trial to Evaluate the Efficacy and Safety of Tolterodine ER in Subjects With Overactive Bladder

Study Overview
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Brief Summary
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To compare the effect of tolterodine ER 4 mg to placebo on patient reported outcomes in subjects with overactive bladder after 1, 4, and 12 weeks of treatment using an innovative web-based trial design

Official Title
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Exploratory, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Single Center, Web-Based Phase IV Pilot Methodology Trial To Evaluate The Efficacy And Safety Of Tolterodine ER In Subjects With Overactive Bladder

Conditions
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Overactive Bladder

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female and 21 years or older Overactive bladder symptoms (subject-reported) for at least 3 months Be resident in the United States of America and have access and be able to use a computer with internet access throughout the duration of the study Exclusion Criteria: Clinically significant hepatic, renal or neurological condition such as stroke (with residual deficit), multiple sclerosis, spinal cord injury, or Parkinson's disease. History of cystitis, continence, urogenitalcancer or radiation Subjects who are pregnant, nursing, or with a positive urine pregnancy test or who are intending to become pregnant within 28 days after the completion of the trial.

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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Female

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 |
| --- | --- |
| Experimental: Tolterodine ER<br> | Drug: Tolterodine ER<br>* One 4 mg capsule will be taken with water every day with or without food. It should be swallowed whole without chewing.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* A placebo of Tolterodine ER 4 mg will be taken with water every day with or without food. It should be swallowed whole without chewing.<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 Micturitions Per 24 Hours at Week 12 | Micturitions include episodes of voluntary micturition and episodes of Urgency Urinary Incontinence (UUI). UUI episodes were defined as those micturitions with Urinary Sensation Scale (USS) rating of 5 in the diary in participants with UUI at baseline. USS rating 5: Unable to hold; leak urine. The mean number of micturitions per 24 hours was calculated as the total number of micturitions divided by the total number of diary days collected at that visit. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Voided Volume Per Micturition at Week 1, 4 and 12 | Mean voided volume per micturition was calculated as sum of voided volume divided by the total number of micturition episodes with a recorded voided volume greater than 0 at that visit. Baseline values for each time point were calculated separately considering only those participants who were evaluable at the given time point. | Baseline, Week 1, 4, 12 | 
| Change From Baseline in Number of Urgency Urinary Incontinence (UUI) Episodes Per 24 Hours at Week 1, 4 and 12 | UUI episodes were defined as those with the Urinary Sensation Scale (USS) rating of 5 in the diary. 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. Baseline values for each time point were calculated separately considering only those participants who were evaluable at the given time point. | Baseline, Week 1, 4, 12 | 
| Change From Baseline in Mean Number of Micturitions Per 24 Hours at Week 1 and 4 | Micturitions include episodes of voluntary micturition and episodes of UUI. UUI episodes were defined as those micturitions with USS rating of 5 in the diary in participants with UUI at baseline. USS rating 5: Unable to hold; leak urine. The mean number of micturitions per 24 hours was calculated as the total number of micturitions divided by the total number of diary days collected at that visit. Baseline values for each time point were calculated separately considering only those participants who were evaluable at the given time point. | Baseline, Week 1, 4 | 
| Change From Baseline in Mean Number of Nocturnal Micturitions Per 24 Hours at Week 1, 4 and 12 | Nocturnal micturitions were defined as micturitions with USS rating 1-5 that occurred between the time the participant went to bed and the 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. The mean number of nocturnal micturitions per 24 hours was calculated as the total number of nocturnal micturitions divided by the total number of diary days collected at that visit. | Baseline, Week 1, 4, 12 | 
| Change From Baseline in Mean Number of Nocturnal Micturition-Related Urgency Episodes Per 24 Hours at Week 1, 4 and 12 | The mean number of micturition-related nocturnal urgency episodes per 24 hours was calculated as the total number of micturitions with USS rating of greater than or equal to (>=) 3 that occurred between time participant went to bed and time participant arose to start next day divided by the total number of days that diary data was collected at that visit. 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. | Baseline, Week 1, 4, 12 | 
| Change From Baseline in Mean Number of Micturition-Related Urgency Episodes Per 24 Hours at Week 1, 4 and 12 | The mean number of micturition-related urgency episodes per 24 hours was calculated as the total number of micturitions with USS rating of >= 3 divided by the total number of days that diary data was collected at that visit. 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. Baseline values for each time point were calculated separately considering only those participants who were evaluable at the given time point. | Baseline, Week 1, 4, 12 | 
| Number of Participants With Change From Baseline in Patient Perception of Bladder Condition (PPBC) at Week 1, 4 and 12 | PPBC: self-administered,single-item questionnaire to describe participant's perception of bladder-related problems. PPBC assessed on 6-point scale:1=no problems at all,2=some very minor problems,3=some minor problems,4=some moderate problems,5=severe problems,6=many severe problems. Results categorized as score change (SC) from baseline on 2-point scale:improvement (negative SC),no improvement (SC 0 or more) and on 4-point scale:major improvement (SC is negative in magnitude of 2 or more), minor improvement (SC is negative in magnitude of 1), no change (SC= 0),deterioration (positive SC). | Baseline, Week 1, 4, 12 | 
| Number of Participants With Change From Baseline in Patient Perception of Urgency Scale (PPUS) at Week 1, 4 and 12 | PPUS: a self-administered, single-item, validated questionnaire that measures the participant's perception of urinary urgency. It is 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 is doing before going to toilet [without leaking]). Results categorized as SC from baseline on 3-point scale: improvement (positive SC), no change (SC 0), deterioration (negative SC). | Baseline (Bl), Week 1, 4, 12 | 
| Change From Baseline in Overactive Bladder Questionnaire (OAB-q) Symptom Bother Score at Week 12 | OAB-q: a self-administered, 33-item, questionnaire that assesses how much the participant has been bothered by selected bladder symptoms. Each item rated by participant on Likert scale 1 (not at all) to 6 (a very great deal). Symptom bother score derived as sum of scores for items 1 to 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. | Baseline, Week 12 | 
| Change From Baseline in Health Related Quality of Life (HRQL) Domains and Total Score of Overactive Bladder Questionnaire (OAB-q) at Week 12 | OAB-q: self-administered, 33-item, questionnaire, assesses how much participant has been bothered by selected bladder symptoms. Each item rated on Likert scale 1 (not at all) to 6 (a very great deal). Questions 9 to 33 constitute HRQL, includes domains (range): concern(7-42), coping(8-48), sleep(5-30), and social function(5-30). Total HRQL score (25-125) derived as sum of HRQL domains. Transformed score range 0 to 100 (HRQL domain or total) = [(Highest possible raw score-Actual total raw score)/Raw score range]*100. Higher transformed scores indicate better HRQL. | Baseline, Week 12 | 
| Change From Baseline in Health Related Quality of Life (HRQL) Social Domain Score at Week 12 | OAB-q: self-administered, 33-item, questionnaire, assesses how much participant has been bothered by selected bladder symptoms. Each item rated on Likert scale 1 (not at all) to 6 (a very great deal). Questions 9 to 33 constitute HRQL, includes domains (range): concern(7-42), coping(8-48), sleep(5-30), and social function(5-30). Total HRQL score (25-125) derived as sum of HRQL domains. Transformed score range 0 to 100 (HRQL domain or total) = [(Highest possible raw score-Actual total raw score)/Raw score range]*100. Higher transformed scores indicate better HRQL. | Baseline, Week 12 | 
| Number of Participants With Response Regarding Source of First Information About Study | Participant experience questionnaire (PEQ) is a web-based self-administered, exploratory questionnaire that assesses the participant's perception of trial method. Number of participants who responded to question 1, Where did you hear first about the study? are reported. | Week 12 | 
| Number of Participants With Reason for Participation in the Study | PEQ is a web-based self-administered, exploratory questionnaire that assesses the participant's perception of trial method. Number of participants who responded to question 2, What led you to participate given the study drug is already available? are reported. | Week 12 | 
| Participant Perception Regarding Satisfaction Related to Study | PEQ:self-administered, to assess perception of trial method. Question3, How satisfied were you with items? on scale 1(very satisfied) to 5(very dissatisfied)- recruitment; questionnaires,surveys(Ques,Sur); identification verification(IV); informed consent(IC) process; website experience; phone call; laboratory(lab) kit delivery; lab location; lab staff service(Ser); physical exam(PE) scheduling,location (sch,loc); PE visit; medication(med) first batch delivery; med second batch delivery; cell phone(CP) received; CP use; call center(CC) ser; medical support(supp); technical supp; overall. | Week 12 | 
| Participant Perception Regarding Cell Phone Diary | PEQ:self-administered, assesses participants perception of trial method. Question4, How satisfied were you with items? on scale 1(very easy) to 5(very difficult)- a: teaching video explaining CP use; recording urinations using CP; size of text on CP; sending your urinary information(inf) using your CP, e: overall, suitability for capturing urinations as they happened. | Week 12 | 
| Participant Perception Regarding Received Treatment in the Study | PEQ is a web-based self-administered, exploratory questionnaire that assesses the participant's perception of trial method. Number of participants who responded to question 5, What treatment did you think you were on? are reported. | Week 12 | 
| Participant Perception Regarding Recommending a Friend to Enter Similar Study | PEQ is a web-based self-administered, exploratory questionnaire that assesses the participant's perception of trial method. Number of participants who responded to question 6, How likely would you be to recommend a friend to enter a similar study? are reported. | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Double-blind, Placebo-controlled, frequency, urgency, web-based, incontinence, methodology, ediary, safety, efficacy, tolerability ER, overactive bladder