Fesoterodine add-on Male Overactive Bladder Study

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of fesoterodine on overactive bladder symptom improvement when added to ongoing alpha blocker treatment.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study To Evaluate The Efficacy And Safety Of Fesoterodine As An Add-On Therapy In Men With Persistent Overactive Bladder Symptoms Under Monotherapy Of Alpha Blocker For Lower Urinary Tract Symptoms.

Conditions
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Overactive Bladder Syndrome

Intervention / Treatment
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* Drug: Fesoterodine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men aged 40 years and above. On a stable and well-tolerated dose of an alpha-blocker prescribed for LUTS for at least 6 weeks prior to screening (Visit 1). Persistent symptoms of OAB with urinary frequency >=8 times/24 hours and micturition-related urgency episodes >=3 episode/24 hours. Exclusion Criteria: Contraindication to fesoterodine (antimuscarinics). Previous history of acute urinary retention requiring catheterization or severe voiding difficulties in the judgment of the investigator, prior to baseline. Unable to follow the study procedures, including completion of self-administered bladder diary and patient reported outcome questionnaires.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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Male

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fesoterodine 4mg or 8mg<br> | Drug: Fesoterodine<br>* Fesoterodine 4mg or 8mg<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numerical Change From Baseline in Micturition-Related Urgency Episodes Per 24 Hours at Week 12 | The mean number of micturition-related urgency episodes per 24 hours was calculated as the total number of micturitions with USS Scale >= 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, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numerical Change From Baseline in Micturition-Related Urgency Episodes Per 24 Hours at Week 4 | The mean number of micturition-related urgency episodes per 24 hours was calculated as the total number of micturitions with USS Scale >= 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, Week 4 | 
| Percentage Change From Baseline in Micturition-Related Urgency Episodes Per 24 Hours at Week 4 and 12 | Micturition-related urgency episodes per 24 hours were defined as those with USS Scale rating of >= 3 marked for the corresponding micturition 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. The percentage change at Week 4 or 12 was calculated as: 100* (Micturition-Related Urgency Episodes at Week 4 or 12 - Baseline)/Baseline | Baseline, Week 4 and 12 | 
| Numerical Change From Baseline in Micturitions Per 24 Hours at Week 4 and 12 | All micturitions with USS rating 1 to 5. 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 micturitions per 24 hours was calculated as the total number of micturitions divided by the total number of diary days collected at that visit. Numeric change of micturitions per 24 hours at Week 4 and 12 relative to Baseline. | Baseline, Week 4 and 12 | 
| Percentage Change From Baseline in Micturitions Per 24 Hours at Week 4 and 12 | All micturitions with USS rating 1 to 5. 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 percentage change at Week 4 or 12 was calculated as: 100* (Micturitions at Week 4 or 12 - Baseline)/Baseline | Baseline, Week 4 and 12 | 
| Numerical Change From Baseline in Nocturnal Micturitions Per 24 Hours at Week 4 and 12 | Nocturnal micturitions were defined as micturitions with USS rating 1-5 that occurred between the time the subject 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 4 and 12 | 
| Percentage Change From Baseline in Nocturnal Micturitions Per 24 Hours at Week 4 and 12 | Nocturnal micturitions were defined as micturitions with USS rating 1-5 that occurred between the time the subject 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 percentage change at Week 4 or 12 was calculated as: 100* (Nocturnal micturitions at Week 4 or 12 - Baseline)/Baseline | Baseline, Week 4 and 12 | 
| Numerical Change From Baseline in Urgency Urinary Incontinence (UUI) Episodes Per 24 Hours at Week 4 and 12 | UUI episodes were defined as those micturitions with USS rating of 5 in the diary in subjects with UUI at baseline. USS rating 5: Unable to hold; leak urine. | Baseline, Week 4 and Week 12 | 
| Percentage Change From Baseline in UUI Episodes Per 24 Hours at Week 4 and 12 | UUI episodes are defined as those micturitions with a USS rating of 5 in the bladder diary in subjects with UUI at baseline. USS rating 5: Unable to hold; leak urine. The percentage change at Week 4 or 12 was calculated as: 100* (UUI Episodes at Week 4 or 12 - Baseline)/Baseline | Baseline, Week 4 and 12 | 
| Numerical Change From Baseline in Severe Micturition-Related Urgency Episodes Per 24 Hours at Week 4 and 12 | Severe micturition related urgency episodes were defined as those micturitions with USS rating >=4 marked for the corresponding micturition in the diary. USS: 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 4 and 12 | 
| Percentage Change From Baseline in Severe Micturition-Related Urgency Episodes Per 24 Hours at Week 4 and 12 | Severe micturition-related urgency episodes are defined as those with a USS rating ≥4 marked for the corresponding micturition in the bladder diary. 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 percentage change at Week 4 or 12 was calculated as: 100* (Severe Micturition-Related Urgency Episodes at Week 4 or 12 - Baseline)/Baseline | Baseline, Week 4 and 12 | 
| Numerical Change From Baseline in Nocturnal Micturition-Related Urgency Episodes Per 24 Hours at Week 4 and 12 | Nocturnal micturition-related urgency episodes were defined as micturition-related urgency episodes with USS ratings 3-5 that occurred between the time the subject 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. | Baseline, Week 4 and 12 | 
| Percentage Change From Baseline in Nocturnal Micturition-Related Urgency Episodes Per 24 Hours at Week 4 and 12 | Nocturnal micturition-related urgency episodes were defined as micturition-related urgency episodes with USS ratings 3-5 that occurred between the time the subject 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 percentage change at Week 4 or 12 was calculated as: 100* (Nocturnal Micturition-Related Urgency Episodes at Week 4 or 12 - Baseline)/Baseline | Baseline, Week 4 and 12 | 
| Numerical Change From Baseline in Urinary Sensation Scale (USS) Sum Rating Per 24 Hours at Week 4 and 12 | The USS sum rating was defined as the total of USS ratings recorded for all micturitions over the course of a day in the bladder diary. 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. USS Sum rating per 24 hours was calculated as the mean rating scores on the USS multiplied by the mean number of micturitions per 24 hours at that visit. | Baseline, Week 4 and 12 | 
| Change From Baseline in International Prostate Symptom Score (IPSS) Total Score (Sum Question 1 [Q1] to Q7) Per 24 Hours at Week 4 and 12 | The IPSS Total Score is obtained by combining the scores of the responses to 1 though 7 component questions. Each question is scored from 0-5 for an IPSS range of 0-35 points; higher numerical scores from the IPSS questionnaire represent greater severity of symptoms. | Baseline, Week 4 and 12 | 
| Change From Baseline in IPSS Storage Domain (Sum Q2, Q4, and Q7) Per 24 Hours at Week 4 and 12 | The IPSS Total Score is obtained by combining the scores of the responses to 1 though 7 component questions. Each question is scored from 0-5. Total IPSS range = 0-35 points; higher numerical scores from the IPSS questionnaire represent greater severity of symptoms. Sum of Q2, Q4, and Q7 range = 0-15 points. | Baseline, Week 4 and 12 | 
| Change From Baseline in IPSS Voiding Domain (Sum Q1, Q3, Q5, and Q6) Per 24 Hours at Week 4 and 12 | The IPSS Total Score is obtained by combining the scores of the responses to 1 though 7 component questions. Each question is scored from 0-5. Total IPSS range = 0-35 points; higher numerical scores from the IPSS questionnaire represent greater severity of symptoms. Sum of Q1, Q3, Q5, and Q6 range = 0-20 points. | Baseline, Week 4 and 12 | 
| Change From Baseline in IPSS Quality of Life (QoL) Score (Q8) Per 24 Hours at Week 4 and 12 | The IPSS Total Score is obtained by combining the scores of the responses to 1 though 7 component questions. Each question is scored from 0-5. Total IPSS range = 0-35 points; higher numerical scores from the IPSS questionnaire represent greater severity of symptoms. Score of Q8 range = 0-5 points. | Baseline, Week 4 and 12 | 
| Change From Baseline in IPSS Individual Item Scores (Q1, Q2, Q3, Q4, Q5, Q6, and Q7) Per 24 Hours at Week 4 | The IPSS Total Score is obtained by combining the scores of the responses to 1 though 7 component questions. Each question is scored from 0-5. Total IPSS range = 0-35 points; higher numerical scores from the IPSS questionnaire represent greater severity of symptoms. | Baseline, Week 4 | 
| Change From Baseline in IPSS Individual Item Scores (Q1, Q2,Q3, Q4, Q5, Q6, and Q7) Per 24 Hours at Week 12 | The IPSS Total Score is obtained by combining the scores of the responses to 1 though 7 component questions. Each question is scored from 0-5 for an IPSS range of 0-35 points; higher numerical scores from the IPSS questionnaire represent greater severity of symptoms. | Baseline, Week 12 | 
| Number of Participants With Change From Baseline in Patient Perception of Bladder Condition (PPBC) Per 24 Hours at Week 4 | PPBC: self-administered, single-item, validated questionnaire. Rated on a 6-point scale: subject was asked: Which of the following statements describes your bladder condition best at the moment? 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. A post-baseline vs baseline variable with ordinal values was derived: 1=Deterioration=Difference in scores was positive; 2=No Change=Difference in scores was 0; 3=Minor Improvement=Difference in scores was -1; 4=Major Improvement=Difference in scores was ≤ 2. | Baseline, Week 4 | 
| Number of Participants With Change From Baseline in PPBC Per 24 Hours at Week 12 | PPBC: self-administered, single-item, validated questionnaire. Rated on a 6-point scale: subject was asked: Which of the following statements describes your bladder condition best at the moment? 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. A post-baseline vs baseline variable with ordinal values was derived: 1=Deterioration=Difference in scores was positive; 2=No Change=Difference in scores was 0; 3=Minor Improvement=Difference in scores was -1; 4=Major Improvement=Difference in scores was ≤ 2. | Baseline, Week 12 | 
| Number of Participants With Change From Baseline in Urgency Perception Scale (UPS) Per 24 Hours at Week 4 | 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 4 | 
| Number of Participants With Change From Baseline in Change From Baseline in UPS Per 24 Hours at Week 12. | 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 12 | 
| Change From Baseline in Overactive Bladder Questionnaire (OAB-q) Per 24 Hours at Week 4 and 12 | OAB-q is a self-administered, 33-item, validated questionnaire that assesses how much the subject has been bothered by selected bladder symptoms during the previous week. Each item rated by subject on Likert scale 1 (least symptom bother) to 6 (most symptom bother). Raw scores were transformed to a score from 0-100. Once transformed, higher scores represent less favorable outcome. | Baseline, Week 4 and 12 | 
| Change From Baseline in Total Score of Each Health Related Quality of Life (HRQL) Domain of OAB-q at Week 4 and 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 range 0 to 100 (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 4 and 12 | 
| Change From Baseline in Score of Each Health Related Quality of Life (HRQL) Domain of OAB-q at Week 4 and 12 (OAB-q Concern Domain) | The HRQL concern domain; range was 0-100. The transformed score for HRQL was calculated based on the following formula: Transformed score (HRQL) = [(Highest possible score - Actual raw score)/ Range]*100, where range was the raw score range. Positive change in HRQL Score indicates improvement. | Baseline, Week 4 and 12 | 
| Change From Baseline in Score of Each Health Related Quality of Life (HRQL) Domain of OAB-q at Week 4 and 12 (OAB-q Coping Domain) | The HRQL coping domain; range was 0-100. The transformed score for HRQL was calculated based on the following formula: Transformed score (HRQL) = [(Highest possible score - Actual raw score)/ Range]*100, where range was the raw score range. Positive change in HRQL Score indicates improvement. | Baseline, Week 4 and Week 12 | 
| Change From Baseline in Score of Each Health Related Quality of Life (HRQL) Domain of OAB-q at Week 4 and 12 (OAB-q Sleep Domain) | The HRQL sleep domain; range was 0-100. The transformed score for HRQL was calculated based on the following formula: Transformed score (HRQL) = [(Highest possible score - Actual raw score)/ Range]*100, where range was the raw score range. Positive change in HRQL Score indicates improvement. | Baseline, Week 4 and Week 12 | 
| Change From Baseline in Score of Each Health Related Quality of Life (HRQL) Domain of OAB-q at Week 4 and 12 (OAB-q Social Interaction Domain) | The HRQL social interaction domain; range was 0-100. The transformed score for HRQL was calculated based on the following formula: Transformed score (HRQL) = [(Highest possible score - Actual raw score)/ Range]*100, where range was the raw score range. Positive change in HRQL Score indicates improvement. | Baseline, Week 4 and Week 12 | 
| Change From Baseline in Post Void Residual (PVR) Urine Volume Per 24 Hours at Week 4, 8 and 12 | Post-void residual volume measurement was measured by an ultrasound at Baseline, and at Weeks 4, 8 and 12. | Baseline, Week 4, 8 and 12 | 
| Change From Baseline in Maximum Urinary Flow Rate (QMAX) Per 24 Hours at Week 12 | Maximum urinary flow rate (Qmax) was recorded at Baseline and Week 12 visit. | Baseline, Week 12 | 
| Number of Participants Reporting Urinary Retention Requiring Catheterization (All Causalities) | Number of participants experiencing serious and non-serious adverse events of acute urinary retention requiring catheterization. | Baseline, Week 12 | 
| Number of Participants Experiencing Adverse Events Related to Increased Voiding Difficulty (All Causalities) | Number of participants experiencing serious and non-serious adverse events related to increased voiding difficulty (ie, Dysuria, Urinary retention regardless of catheterization, Urine flow decreased, Residual urine volume, Residual urine volume increased, Residual urine, and Urinary hesitation) | Baseline, Week 12 |