Overactive Bladder
Conditions
Keywords
Overactive Bladder
Brief summary
This Phase 3B study is designed to test if a fesoterodine flexible dose regimen is more effective than placebo in reducing micturition frequency and other overactive bladder (OAB) symptoms, e.g., urgency, urgency incontinence episodes in patients with overactive bladder and if the fesoterodine regimen is safe and well tolerated.
Interventions
DRUGFesoterodine
4mg tablets once daily for 2 weeks, then either 4mg or 8mg tablets once daily for 10 weeks. Subjects were instructed to take 1 tablet every evening within 4 hours prior to bedtime with water, swallowed whole without chewing.
DRUGPlacebo
Matched placebo tablets once daily for 12 weeks. Subjects were instructed to take 1 tablet every evening within 4 hours prior to bedtime with water, swallowed whole without chewing.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Overactive bladder symptoms for greater than or equal to 3 months. * Mean urinary frequency of greater than or equal to 8 micturitions per 24 hours in bladder diary. * Mean number of Urgency episodes greater than or equal to 3 per 24 hours in bladder diary.
Exclusion criteria
* Contraindication to fesoterodine (antimuscarinics). * Known etiology of OAB (e.g., neurogenic, local urinary tract pathology). * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Number of Micturition Episodes Per 24 Hours at Week 12 Relative to Baseline. | Baseline and Week 12 | The number of micturitions per 24 hours was calculated as the sum of all micturitions divided by the total number of diary days collected at that visit. Change: mean at Week 12 minus mean at Baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Number of Urgency Episodes Per 24 Hours Relative to Baseline | Baseline, Week 2, Week 6 and Week 12 | Change in number of urgency episodes (urinary sensation scale \[USS\] rating of 3 or more) recorded in the bladder diary. Scale: 0=no feeling of urgency to 5=unable to hold; leak urine. The number of urgency episodes per 24 hours was calculated as the sum of all urgency episodes divided by the total number of diary days collected at that visit. |
| Change in Number of Severe Urgency Episodes Per 24 Hours Relative to Baseline | Baseline, Week 2, Week 6 and Week 12 | Change in number of severe urgency episodes (urinary sensation scale \[USS\] rating of 4 or more) recorded in the bladder diary. Scale: 0=no feeling of urgency to 5=unable to hold; leak urine. Number of severe urgency episodes per 24 hours calculated as sum of all severe urgency episodes divided by total number of diary days collected at that visit. |
| Change in Number of Urgency Urinary Incontinence (UUI) Episodes Per 24 Hours Relative to Baseline | Baseline, Week 2, Week 6 and Week 12 | Change in number of UUI episodes (urinary sensation scale \[USS\] rating of 5) recorded in the bladder diary. Scale: 0=no feeling of urgency to 5=unable to hold; leak urine |
| Change in Nocturnal Micturition Episodes Per 24 Hours Relative to Baseline | Baseline, Week 2, Week 6 and Week 12 | Change in number of nocturnal micturitions (NM) recorded in the bladder diary. NM were defined as micturitions that occurred between the time the subject went to bed and the time he or she arose to start the next day. The number of NM per 24 hours was calculated as the sum of all NM divided by the total number of diary days collected at that visit. |
| Change in Number of Nocturnal Urgency Episodes Per 24 Hours Relative to Baseline | Baseline, Week 2, Week 6 and Week 12 | Change in number of nocturnal urgency episodes (NUE) recorded in bladder diary. NUE had urinary sensation scale (USS) rating of 3 or more that occurred between time subject went to bed and time he or she arose to start next day. Number of NUE per 24 hours was calculated as sum of all NUE divided by total number of diary days collected at that visit |
| Change in Mean Number of Micturition Episodes Per 24 Hours Relative to Baseline | Baseline, Week 2 and Week 6 | The number of micturitions per 24 hours was calculated as the sum of all micturitions divided by the total number of diary days collected at that visit. Change: mean at observation minus mean at baseline |
| Change in Overactive Bladder Questionnaire (OAB-q) at Week 12 Relative to Baseline - Symptom Bother Scale | Baseline and Week 12 | Each item rated by subject on a Likert scale 1 (least symptom bother) to 6 (most symptom bother). Raw scores were transformed to a score from 0 to 100. Once transformed a negative change indicates improvement. Change: mean at Week 12 minus mean at baseline |
| Change in Overactive Bladder Questionnaire (OAB-q) at Week 12 Relative to Baseline - Health Related Quality of Life (HRQL) Subscales | Baseline and Week 12 | Each item rated by subject on a Likert scale 1 (least symptom bother) to 6 (most symptom bother). Raw scores were transformed to a score from 0 to 100. Once transformed a positive change indicates improvement. Change: mean at Week 12 minus mean at baseline. |
| Categorical Change in Patient Perception of Bladder Condition (PPBC) Score Relative to Baseline | Baseline, Week 2, Week 6 and Week 12 | PPBC scale range: 1='does not cause me any problems at all' to 6='causes me many severe problems'. Major improvement=negative score change of 2 or more from baseline; minor improvement=negative score change of 1 or more from baseline; no change=0 score change from baseline; Deterioration=positive score change from baseline |
| Categorical Change in Urgency Perception Scale (UPS) Relative to Baseline | Baseline, Week 2, Week 6 and Week 12 | UPS scores range from 0 (I am usually not able to hold urine) to 2 (I am usually able to finish what I am doing before going to the toilet \[without leaking\]). Improvement: positive score change; No change: score change=0; Deterioration: negative score change |
| Change in Urgency Severity Visual Analog Scale (VAS) Relative to Baseline | Baseline, Week 2, Week 6 and Week 12 | The urgency severity VAS Scale records the subject's assessment of the severity of urgency. VAS scale ranges from 1 'Very Mild' to 10 'Very Severe'. Negative change indicated improvement. Change: mean at observation minus mean at baseline. |
| Change in Frequency-urgency Sum Per 24 Hours Relative to Baseline | Baseline, Week 2, Week 6 and Week 12 | Change in frequency urgency sum is total urinary sensation scale (USS) ratings recorded for all micturitions in 24-hour day. Number of USS ratings per 24 hours is sum of all USS ratings divided by the total diary days collected at that visit. USS scale: 1=No feeling of urgency to 5=Unable to hold:leak urine. Numerical decrease indicates improvement |
Countries
United States
Participant flow
Recruitment details
Participants were screened at 90 centers in the United States; in 88 centers, participants were randomized.
Pre-assignment details
The study consisted of a 2-week no-treatment screening period and a 12-week double-blind treatment period. Participants with bothersome overactive bladder (OAB) symptoms who met all entry criteria at baseline (end of screening) were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Placebo All randomized participants were treated with placebo once daily for the first 2 weeks of treatment. The dose remained as placebo once daily or changed to matching placebo (for 8 mg) once daily for the next 10 weeks based on discussion between investigator and participant. | 445 |
| Fesoterodine All randomized participants were treated with fesoterodine 4mg once daily for the first 2 weeks of treatment. The dose remained at 4 mg once daily or increased to 8 mg once daily for the next 10 weeks based on discussion between investigator and participant. | 438 |
| Total | 883 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 21 | 34 |
| Overall Study | Lack of Efficacy | 16 | 5 |
| Overall Study | Lost to Follow-up | 8 | 6 |
| Overall Study | Other | 4 | 0 |
| Overall Study | Withdrawal by Subject | 11 | 11 |
Baseline characteristics
| Characteristic | Placebo | Fesoterodine | Total |
|---|---|---|---|
| Age Continuous | 60.1 years STANDARD_DEVIATION 12.9 | 59.7 years STANDARD_DEVIATION 13.7 | 59.9 years STANDARD_DEVIATION 13.3 |
| Sex: Female, Male Female | 368 Participants | 364 Participants | 732.0 Participants |
| Sex: Female, Male Male | 77 Participants | 74 Participants | 151.0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 130 / — | 199 / — |
| serious Total, serious adverse events | 7 / — | 5 / — |
Outcome results
Primary
Change in Mean Number of Micturition Episodes Per 24 Hours at Week 12 Relative to Baseline.
The number of micturitions per 24 hours was calculated as the sum of all micturitions divided by the total number of diary days collected at that visit. Change: mean at Week 12 minus mean at Baseline
Time frame: Baseline and Week 12
Population: Participants in the Full Analysis Set (FAS) with non-missing numerical change from baseline to Week 12 (last observation carried forward \[LOCF)). The FAS included all participants who took at least 1 dose of assigned study drug and had at least 1 valid efficacy assessment, either at baseline or post baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Mean Number of Micturition Episodes Per 24 Hours at Week 12 Relative to Baseline. | -2.1 number of episodes per 24 hours | Standard Error 0.1 |
| Fesoterodine | Change in Mean Number of Micturition Episodes Per 24 Hours at Week 12 Relative to Baseline. | -2.9 number of episodes per 24 hours | Standard Error 0.1 |
Comparison: Null hypothesis: the mean change from baseline in micturitions per 24 hours in the fesoterodine group is the same as in the placebo group at Week 12. A sample size of 350 in each arm had at least 85% power to detect a difference of 0.8 between flexible dose fesoterodine \& placebo assuming a standard deviation of 3.52 using a 2-sample t-test with a 0.05 2-sided significance level. Accounting for 10% of randomized subjects not having the primary endpoint data, 390 subjects were needed in each armp-value: 0.000295% CI: [-1.1, -0.4]ANCOVA
Secondary
Categorical Change in Patient Perception of Bladder Condition (PPBC) Score Relative to Baseline
PPBC scale range: 1='does not cause me any problems at all' to 6='causes me many severe problems'. Major improvement=negative score change of 2 or more from baseline; minor improvement=negative score change of 1 or more from baseline; no change=0 score change from baseline; Deterioration=positive score change from baseline
Time frame: Baseline, Week 2, Week 6 and Week 12
Population: Participants in the Full Analysis Set (FAS) with non-missing baseline values and Week 2, Week 6 (last observation carried forward \[LOCF\]) or Week 12 (LOCF) values.~Number analyzed=participants at Week 12 LOCF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Categorical Change in Patient Perception of Bladder Condition (PPBC) Score Relative to Baseline | Week 2 (n=440; n=434): major improvement | 13.2 percentage of participants |
| Placebo | Categorical Change in Patient Perception of Bladder Condition (PPBC) Score Relative to Baseline | Week 2: minor improvement | 34.8 percentage of participants |
| Placebo | Categorical Change in Patient Perception of Bladder Condition (PPBC) Score Relative to Baseline | Week 2: no change | 45.2 percentage of participants |
| Placebo | Categorical Change in Patient Perception of Bladder Condition (PPBC) Score Relative to Baseline | Week 2: deterioration | 6.8 percentage of participants |
| Placebo | Categorical Change in Patient Perception of Bladder Condition (PPBC) Score Relative to Baseline | Week 6 (n=442; n=435): major improvement | 24.7 percentage of participants |
| Placebo | Categorical Change in Patient Perception of Bladder Condition (PPBC) Score Relative to Baseline | Week 6: minor improvement | 34.8 percentage of participants |
| Placebo | Categorical Change in Patient Perception of Bladder Condition (PPBC) Score Relative to Baseline | Week 6: no change | 33.5 percentage of participants |
| Placebo | Categorical Change in Patient Perception of Bladder Condition (PPBC) Score Relative to Baseline | Week 6: deterioration | 7.0 percentage of participants |
| Placebo | Categorical Change in Patient Perception of Bladder Condition (PPBC) Score Relative to Baseline | Week 12 (n=442; n=435): major improvement | 29.2 percentage of participants |
| Placebo | Categorical Change in Patient Perception of Bladder Condition (PPBC) Score Relative to Baseline | Week 12: minor improvement | 31.0 percentage of participants |
| Placebo | Categorical Change in Patient Perception of Bladder Condition (PPBC) Score Relative to Baseline | Week 12: no change | 33.0 percentage of participants |
| Placebo | Categorical Change in Patient Perception of Bladder Condition (PPBC) Score Relative to Baseline | Week 12: deterioration | 6.8 percentage of participants |
| Fesoterodine | Categorical Change in Patient Perception of Bladder Condition (PPBC) Score Relative to Baseline | Week 12: no change | 25.5 percentage of participants |
| Fesoterodine | Categorical Change in Patient Perception of Bladder Condition (PPBC) Score Relative to Baseline | Week 2 (n=440; n=434): major improvement | 16.6 percentage of participants |
| Fesoterodine | Categorical Change in Patient Perception of Bladder Condition (PPBC) Score Relative to Baseline | Week 6: no change | 27.8 percentage of participants |
| Fesoterodine | Categorical Change in Patient Perception of Bladder Condition (PPBC) Score Relative to Baseline | Week 2: minor improvement | 39.4 percentage of participants |
| Fesoterodine | Categorical Change in Patient Perception of Bladder Condition (PPBC) Score Relative to Baseline | Week 12: minor improvement | 34.5 percentage of participants |
| Fesoterodine | Categorical Change in Patient Perception of Bladder Condition (PPBC) Score Relative to Baseline | Week 2: no change | 39.4 percentage of participants |
| Fesoterodine | Categorical Change in Patient Perception of Bladder Condition (PPBC) Score Relative to Baseline | Week 6: deterioration | 3.9 percentage of participants |
| Fesoterodine | Categorical Change in Patient Perception of Bladder Condition (PPBC) Score Relative to Baseline | Week 2: deterioration | 4.6 percentage of participants |
| Fesoterodine | Categorical Change in Patient Perception of Bladder Condition (PPBC) Score Relative to Baseline | Week 12: deterioration | 3.2 percentage of participants |
| Fesoterodine | Categorical Change in Patient Perception of Bladder Condition (PPBC) Score Relative to Baseline | Week 6 (n=442; n=435): major improvement | 32.4 percentage of participants |
| Fesoterodine | Categorical Change in Patient Perception of Bladder Condition (PPBC) Score Relative to Baseline | Week 12 (n=442; n=435): major improvement | 36.8 percentage of participants |
| Fesoterodine | Categorical Change in Patient Perception of Bladder Condition (PPBC) Score Relative to Baseline | Week 6: minor improvement | 35.9 percentage of participants |
Comparison: Treatment difference at Week 2p-value: 0.0087Cochran-Mantel-Haenszel
Comparison: Treatment difference at Week 6p-value: 0.0008Cochran-Mantel-Haenszel
Comparison: Treatment difference at Week 12p-value: 0.0006Cochran-Mantel-Haenszel
Secondary
Categorical Change in Urgency Perception Scale (UPS) Relative to Baseline
UPS scores range from 0 (I am usually not able to hold urine) to 2 (I am usually able to finish what I am doing before going to the toilet \[without leaking\]). Improvement: positive score change; No change: score change=0; Deterioration: negative score change
Time frame: Baseline, Week 2, Week 6 and Week 12
Population: Participants in the Full Analysis Set (FAS) with non-missing baseline values and Week 2, Week 6 (last observation carried forward \[LOCF\]) or Week 12 (LOCF) values.~Number analyzed=participants at Week 12 LOCF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Categorical Change in Urgency Perception Scale (UPS) Relative to Baseline | Week 6: no change | 65.0 percentage of participants |
| Placebo | Categorical Change in Urgency Perception Scale (UPS) Relative to Baseline | Week 2: deterioration | 7.9 percentage of participants |
| Placebo | Categorical Change in Urgency Perception Scale (UPS) Relative to Baseline | Week 6: deterioration | 4.7 percentage of participants |
| Placebo | Categorical Change in Urgency Perception Scale (UPS) Relative to Baseline | Week 12 (n=443; n=435): improvement | 30.9 percentage of participants |
| Placebo | Categorical Change in Urgency Perception Scale (UPS) Relative to Baseline | Week 2: no change | 69.2 percentage of participants |
| Placebo | Categorical Change in Urgency Perception Scale (UPS) Relative to Baseline | Week 12: no change | 62.3 percentage of participants |
| Placebo | Categorical Change in Urgency Perception Scale (UPS) Relative to Baseline | Week 6 (n=443; n=435): improvement | 30.2 percentage of participants |
| Placebo | Categorical Change in Urgency Perception Scale (UPS) Relative to Baseline | Week 12: deterioration | 6.8 percentage of participants |
| Placebo | Categorical Change in Urgency Perception Scale (UPS) Relative to Baseline | Week 2 (n=441; n=434): improvement | 22.9 percentage of participants |
| Fesoterodine | Categorical Change in Urgency Perception Scale (UPS) Relative to Baseline | Week 12: deterioration | 5.7 percentage of participants |
| Fesoterodine | Categorical Change in Urgency Perception Scale (UPS) Relative to Baseline | Week 2 (n=441; n=434): improvement | 29.3 percentage of participants |
| Fesoterodine | Categorical Change in Urgency Perception Scale (UPS) Relative to Baseline | Week 2: no change | 64.5 percentage of participants |
| Fesoterodine | Categorical Change in Urgency Perception Scale (UPS) Relative to Baseline | Week 2: deterioration | 6.2 percentage of participants |
| Fesoterodine | Categorical Change in Urgency Perception Scale (UPS) Relative to Baseline | Week 6 (n=443; n=435): improvement | 37.5 percentage of participants |
| Fesoterodine | Categorical Change in Urgency Perception Scale (UPS) Relative to Baseline | Week 6: no change | 58.6 percentage of participants |
| Fesoterodine | Categorical Change in Urgency Perception Scale (UPS) Relative to Baseline | Week 12 (n=443; n=435): improvement | 41.8 percentage of participants |
| Fesoterodine | Categorical Change in Urgency Perception Scale (UPS) Relative to Baseline | Week 12: no change | 52.4 percentage of participants |
| Fesoterodine | Categorical Change in Urgency Perception Scale (UPS) Relative to Baseline | Week 6: deterioration | 3.9 percentage of participants |
Comparison: Treatment difference at Week 2p-value: 0.0129Cochran-Mantel-Haenszel
Comparison: Treatment difference at Week 6p-value: 0.01Cochran-Mantel-Haenszel
Comparison: Treatment difference at Week 12p-value: 0.0009Cochran-Mantel-Haenszel
Secondary
Change in Frequency-urgency Sum Per 24 Hours Relative to Baseline
Change in frequency urgency sum is total urinary sensation scale (USS) ratings recorded for all micturitions in 24-hour day. Number of USS ratings per 24 hours is sum of all USS ratings divided by the total diary days collected at that visit. USS scale: 1=No feeling of urgency to 5=Unable to hold:leak urine. Numerical decrease indicates improvement
Time frame: Baseline, Week 2, Week 6 and Week 12
Population: Participants in the Full Analysis Set (FAS) with non-missing numerical change from baseline to Week 2, Week 6 or Week 12 (last observation carried forward \[LOCF\]).~Number analyzed=participants at Week 12 LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Frequency-urgency Sum Per 24 Hours Relative to Baseline | Week 2 (n=431; n=427) | -6.5 scores on a scale | Standard Error 0.5 |
| Placebo | Change in Frequency-urgency Sum Per 24 Hours Relative to Baseline | Week 6 (n=434; n=428) | -9.8 scores on a scale | Standard Error 0.6 |
| Placebo | Change in Frequency-urgency Sum Per 24 Hours Relative to Baseline | Week 12 (n=434; n=428) | -10.3 scores on a scale | Standard Error 0.6 |
| Fesoterodine | Change in Frequency-urgency Sum Per 24 Hours Relative to Baseline | Week 2 (n=431; n=427) | -8.3 scores on a scale | Standard Error 0.5 |
| Fesoterodine | Change in Frequency-urgency Sum Per 24 Hours Relative to Baseline | Week 6 (n=434; n=428) | -12.5 scores on a scale | Standard Error 0.6 |
| Fesoterodine | Change in Frequency-urgency Sum Per 24 Hours Relative to Baseline | Week 12 (n=434; n=428) | -13.6 scores on a scale | Standard Error 0.6 |
Comparison: Week 2 minus Baselinep-value: 0.020395% CI: [-3.2, -0.3]ANCOVA
Comparison: Week 6 minus Baselinep-value: 0.000795% CI: [-4.2, -1.1]ANCOVA
Comparison: Week 12 minus Baselinep-value: <0.000195% CI: [-4.9, -1.7]ANCOVA
Secondary
Change in Mean Number of Micturition Episodes Per 24 Hours Relative to Baseline
The number of micturitions per 24 hours was calculated as the sum of all micturitions divided by the total number of diary days collected at that visit. Change: mean at observation minus mean at baseline
Time frame: Baseline, Week 2 and Week 6
Population: Participants in the Full Analysis Set (FAS) with non-missing numerical change from baseline to Week 2 or Week 6 (last observation carried forward \[LOCF\]).~The FAS included all participants who took at least 1 dose of assigned study drug and had at least 1 valid efficacy assessment, either at baseline or post baseline (n=placebo; n=fesoterodine)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Mean Number of Micturition Episodes Per 24 Hours Relative to Baseline | Week 2 (n=431; n=427) | -1.3 number of episodes per 24 hours | Standard Error 0.1 |
| Placebo | Change in Mean Number of Micturition Episodes Per 24 Hours Relative to Baseline | Week 6 (n=434; n=428) | -2.0 number of episodes per 24 hours | Standard Error 0.1 |
| Fesoterodine | Change in Mean Number of Micturition Episodes Per 24 Hours Relative to Baseline | Week 2 (n=431; n=427) | -1.8 number of episodes per 24 hours | Standard Error 0.1 |
| Fesoterodine | Change in Mean Number of Micturition Episodes Per 24 Hours Relative to Baseline | Week 6 (n=434; n=428) | -2.7 number of episodes per 24 hours | Standard Error 0.1 |
Comparison: Week 2 minus Baselinep-value: 0.013695% CI: [-0.8, -0.1]ANCOVA
Comparison: Week 6 minus Baselinep-value: 0.000295% CI: [-1.1, -0.3]ANCOVA
Secondary
Change in Nocturnal Micturition Episodes Per 24 Hours Relative to Baseline
Change in number of nocturnal micturitions (NM) recorded in the bladder diary. NM were defined as micturitions that occurred between the time the subject went to bed and the time he or she arose to start the next day. The number of NM per 24 hours was calculated as the sum of all NM divided by the total number of diary days collected at that visit.
Time frame: Baseline, Week 2, Week 6 and Week 12
Population: Number of subjects with Baseline Nocturnal Micturitions \>0 per 24 and non-missing change from baseline to Week 2, Week 6 (last observation carried forward \[LOCF\]) or Week 12 (LOCF). Only subjects with at least 1 episode during baseline 3-day diary period were included in analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Nocturnal Micturition Episodes Per 24 Hours Relative to Baseline | Week 2 (n=420; n=417) | -0.5 number of episodes per 24 hours | Standard Error 0.1 |
| Placebo | Change in Nocturnal Micturition Episodes Per 24 Hours Relative to Baseline | Week 6 (n=423; n=418) | -0.7 number of episodes per 24 hours | Standard Error 0.1 |
| Placebo | Change in Nocturnal Micturition Episodes Per 24 Hours Relative to Baseline | Week 12 (n=423; n=418) | -0.7 number of episodes per 24 hours | Standard Error 0.1 |
| Fesoterodine | Change in Nocturnal Micturition Episodes Per 24 Hours Relative to Baseline | Week 2 (n=420; n=417) | -0.5 number of episodes per 24 hours | Standard Error 0.1 |
| Fesoterodine | Change in Nocturnal Micturition Episodes Per 24 Hours Relative to Baseline | Week 6 (n=423; n=418) | -0.7 number of episodes per 24 hours | Standard Error 0.1 |
| Fesoterodine | Change in Nocturnal Micturition Episodes Per 24 Hours Relative to Baseline | Week 12 (n=423; n=418) | -0.8 number of episodes per 24 hours | Standard Error 0.1 |
Comparison: Week 2 minus Baselinep-value: 0.801995% CI: [-0.2, 0.1]ANOVA
Comparison: Week 6 minus Baselinep-value: 0.388195% CI: [-0.2, 0.1]ANOVA
Comparison: Week 12 minus Baselinep-value: 0.32495% CI: [-0.2, 0.1]ANOVA
Secondary
Change in Number of Nocturnal Urgency Episodes Per 24 Hours Relative to Baseline
Change in number of nocturnal urgency episodes (NUE) recorded in bladder diary. NUE had urinary sensation scale (USS) rating of 3 or more that occurred between time subject went to bed and time he or she arose to start next day. Number of NUE per 24 hours was calculated as sum of all NUE divided by total number of diary days collected at that visit
Time frame: Baseline, Week 2, Week 6 and Week 12
Population: Number of subjects with Nocturnal Urgency Episodes \>0 per 24 hours and non-missing change from baseline to Week 2, Week 6 (last observation carried forward \[LOCF\]) or Week 12 (LOCF). Only subjects with at least 1 episode during baseline 3-day diary period were included in analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Number of Nocturnal Urgency Episodes Per 24 Hours Relative to Baseline | Week 2 (n=411; n=408) | -0.6 number of episodes per 24 hours | Standard Error 0.1 |
| Placebo | Change in Number of Nocturnal Urgency Episodes Per 24 Hours Relative to Baseline | Week 6 (n=414; n=409) | -0.8 number of episodes per 24 hours | Standard Error 0.1 |
| Placebo | Change in Number of Nocturnal Urgency Episodes Per 24 Hours Relative to Baseline | Week 12 (n=414; n=409) | -0.9 number of episodes per 24 hours | Standard Error 0.1 |
| Fesoterodine | Change in Number of Nocturnal Urgency Episodes Per 24 Hours Relative to Baseline | Week 2 (n=411; n=408) | -0.6 number of episodes per 24 hours | Standard Error 0.1 |
| Fesoterodine | Change in Number of Nocturnal Urgency Episodes Per 24 Hours Relative to Baseline | Week 6 (n=414; n=409) | -0.9 number of episodes per 24 hours | Standard Error 0.1 |
| Fesoterodine | Change in Number of Nocturnal Urgency Episodes Per 24 Hours Relative to Baseline | Week 12 (n=414; n=409) | -1.0 number of episodes per 24 hours | Standard Error 0.1 |
Comparison: Week 12 minus Baselinep-value: 0.080695% CI: [-0.4, 0]ANOVA
Comparison: Week 2 minus Baselinep-value: 0.827995% CI: [-0.2, 0.1]ANOVA
Comparison: Week 6 minus Baselinep-value: 0.505995% CI: [-0.2, 0.1]ANOVA
Secondary
Change in Number of Severe Urgency Episodes Per 24 Hours Relative to Baseline
Change in number of severe urgency episodes (urinary sensation scale \[USS\] rating of 4 or more) recorded in the bladder diary. Scale: 0=no feeling of urgency to 5=unable to hold; leak urine. Number of severe urgency episodes per 24 hours calculated as sum of all severe urgency episodes divided by total number of diary days collected at that visit.
Time frame: Baseline, Week 2, Week 6 and Week 12
Population: Number of subjects with baseline severe urgency episodes \>0 per 24 hours and non-missing change from baseline to Week 2, Week 6 (last observation carried forward \[LOCF\]) or Week 12 (LOCF). Only those with at least 1 episode during baseline 3-day diary period were included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Number of Severe Urgency Episodes Per 24 Hours Relative to Baseline | Week 2 (n=393; n=403) | -1.6 number of episodes per 24 hours | Standard Error 0.1 |
| Placebo | Change in Number of Severe Urgency Episodes Per 24 Hours Relative to Baseline | Week 6 (n=396; n=404) | -2.2 number of episodes per 24 hours | Standard Error 0.1 |
| Placebo | Change in Number of Severe Urgency Episodes Per 24 Hours Relative to Baseline | Week 12 (n=396; n=404) | -2.2 number of episodes per 24 hours | Standard Error 0.1 |
| Fesoterodine | Change in Number of Severe Urgency Episodes Per 24 Hours Relative to Baseline | Week 2 (n=393; n=403) | -1.8 number of episodes per 24 hours | Standard Error 0.1 |
| Fesoterodine | Change in Number of Severe Urgency Episodes Per 24 Hours Relative to Baseline | Week 6 (n=396; n=404) | -2.6 number of episodes per 24 hours | Standard Error 0.1 |
| Fesoterodine | Change in Number of Severe Urgency Episodes Per 24 Hours Relative to Baseline | Week 12 (n=396; n=404) | -2.9 number of episodes per 24 hours | Standard Error 0.1 |
Comparison: Week 2 minus Baselinep-value: 0.166695% CI: [-0.6, 0.1]ANCOVA
Comparison: Week 6 minus Baselinep-value: 0.050695% CI: [-0.8, 0]ANCOVA
Comparison: Week 12 minus Baselinep-value: 0.001495% CI: [-1, -0.2]ANCOVA
Secondary
Change in Number of Urgency Episodes Per 24 Hours Relative to Baseline
Change in number of urgency episodes (urinary sensation scale \[USS\] rating of 3 or more) recorded in the bladder diary. Scale: 0=no feeling of urgency to 5=unable to hold; leak urine. The number of urgency episodes per 24 hours was calculated as the sum of all urgency episodes divided by the total number of diary days collected at that visit.
Time frame: Baseline, Week 2, Week 6 and Week 12
Population: Number of subjects with Baseline Urgency Episodes \>0 per 24 hours and non missing change from baseline to Week 2, Week 6 (last observation carried forward \[LOCF\]) or Week 12 (LOCF). Only subjects with at least 1 episode during baseline 3-day diary period were included in analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Number of Urgency Episodes Per 24 Hours Relative to Baseline | Week 2 (n=431; n=427) | -1.9 number of episodes per 24 hours | Standard Error 0.2 |
| Placebo | Change in Number of Urgency Episodes Per 24 Hours Relative to Baseline | Week 6 (n=434; n=428) | -2.9 number of episodes per 24 hours | Standard Error 0.2 |
| Placebo | Change in Number of Urgency Episodes Per 24 Hours Relative to Baseline | Week 12 (n=434; n=428) | -3.0 number of episodes per 24 hours | Standard Error 0.2 |
| Fesoterodine | Change in Number of Urgency Episodes Per 24 Hours Relative to Baseline | Week 2 (n=431; n=427) | -2.3 number of episodes per 24 hours | Standard Error 0.2 |
| Fesoterodine | Change in Number of Urgency Episodes Per 24 Hours Relative to Baseline | Week 6 (n=434; n=428) | -3.5 number of episodes per 24 hours | Standard Error 0.2 |
| Fesoterodine | Change in Number of Urgency Episodes Per 24 Hours Relative to Baseline | Week 12 (n=434; n=428) | -4.0 number of episodes per 24 hours | Standard Error 0.2 |
Comparison: Week 2 minus Baselinep-value: 0.105795% CI: [-0.9, 0.1]ANCOVA
Comparison: Week 6 minus Baselinep-value: 0.033895% CI: [-1.1, 0]ANCOVA
Comparison: Week 12 minus Baselinep-value: 0.000395% CI: [-1.5, -0.5]ANCOVA
Secondary
Change in Number of Urgency Urinary Incontinence (UUI) Episodes Per 24 Hours Relative to Baseline
Change in number of UUI episodes (urinary sensation scale \[USS\] rating of 5) recorded in the bladder diary. Scale: 0=no feeling of urgency to 5=unable to hold; leak urine
Time frame: Baseline, Week 2, Week 6 and Week 12
Population: Number of subjects with Baseline UUI \>0 per 24 hours and non-missing change from baseline to Week 2, Week 6 (last observation carried forward \[LOCF\]) or Week 12 (LOCF). Only subjects with at least 1 episode during baseline 3-day diary period were included in analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Number of Urgency Urinary Incontinence (UUI) Episodes Per 24 Hours Relative to Baseline | Week 2 (n=255; n=251) | -0.9 number of episodes per 24 hours | Standard Error 0.1 |
| Placebo | Change in Number of Urgency Urinary Incontinence (UUI) Episodes Per 24 Hours Relative to Baseline | Week 6 (n=257; n=251) | -1.2 number of episodes per 24 hours | Standard Error 0.1 |
| Placebo | Change in Number of Urgency Urinary Incontinence (UUI) Episodes Per 24 Hours Relative to Baseline | week 12 (n=257; n=251) | -1.2 number of episodes per 24 hours | Standard Error 0.1 |
| Fesoterodine | Change in Number of Urgency Urinary Incontinence (UUI) Episodes Per 24 Hours Relative to Baseline | Week 2 (n=255; n=251) | -1.1 number of episodes per 24 hours | Standard Error 0.1 |
| Fesoterodine | Change in Number of Urgency Urinary Incontinence (UUI) Episodes Per 24 Hours Relative to Baseline | Week 6 (n=257; n=251) | -1.5 number of episodes per 24 hours | Standard Error 0.1 |
| Fesoterodine | Change in Number of Urgency Urinary Incontinence (UUI) Episodes Per 24 Hours Relative to Baseline | week 12 (n=257; n=251) | -1.5 number of episodes per 24 hours | Standard Error 0.1 |
Comparison: Week 2 minus Baselinep-value: 0.205495% CI: [-0.4, 0.1]ANCOVA
Comparison: Week 6 minus Baselinep-value: 0.022595% CI: [-0.6, 0]ANCOVA
Comparison: Week 12 minus Baselinep-value: 0.016795% CI: [-0.6, -0.1]ANCOVA
Secondary
Change in Overactive Bladder Questionnaire (OAB-q) at Week 12 Relative to Baseline - Health Related Quality of Life (HRQL) Subscales
Each item rated by subject on a Likert scale 1 (least symptom bother) to 6 (most symptom bother). Raw scores were transformed to a score from 0 to 100. Once transformed a positive change indicates improvement. Change: mean at Week 12 minus mean at baseline.
Time frame: Baseline and Week 12
Population: Participants in the Full Analysis Set (FAS) with non-missing numerical change from baseline to Week 12.~The FAS included all participants who took at least 1 dose of assigned study drug and had at least 1 valid efficacy assessment, either at baseline or post baseline
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Overactive Bladder Questionnaire (OAB-q) at Week 12 Relative to Baseline - Health Related Quality of Life (HRQL) Subscales | HRQL coping domain (n=383; n=372) | 20.2 scores on a scale | Standard Error 1.2 |
| Placebo | Change in Overactive Bladder Questionnaire (OAB-q) at Week 12 Relative to Baseline - Health Related Quality of Life (HRQL) Subscales | HRQL social interaction domain (n=380; n=372) | 11.6 scores on a scale | Standard Error 0.8 |
| Placebo | Change in Overactive Bladder Questionnaire (OAB-q) at Week 12 Relative to Baseline - Health Related Quality of Life (HRQL) Subscales | HRQL sleep domain (n=383; n=372) | 21.2 scores on a scale | Standard Error 1.2 |
| Placebo | Change in Overactive Bladder Questionnaire (OAB-q) at Week 12 Relative to Baseline - Health Related Quality of Life (HRQL) Subscales | HRQL scale score total (n=380; n=372) | 18.9 scores on a scale | Standard Error 1 |
| Placebo | Change in Overactive Bladder Questionnaire (OAB-q) at Week 12 Relative to Baseline - Health Related Quality of Life (HRQL) Subscales | HRQL concern domain (n=383; n=372) | 20.9 scores on a scale | Standard Error 1.1 |
| Fesoterodine | Change in Overactive Bladder Questionnaire (OAB-q) at Week 12 Relative to Baseline - Health Related Quality of Life (HRQL) Subscales | HRQL scale score total (n=380; n=372) | 25.1 scores on a scale | Standard Error 1 |
| Fesoterodine | Change in Overactive Bladder Questionnaire (OAB-q) at Week 12 Relative to Baseline - Health Related Quality of Life (HRQL) Subscales | HRQL concern domain (n=383; n=372) | 29.3 scores on a scale | Standard Error 1.2 |
| Fesoterodine | Change in Overactive Bladder Questionnaire (OAB-q) at Week 12 Relative to Baseline - Health Related Quality of Life (HRQL) Subscales | HRQL coping domain (n=383; n=372) | 27.2 scores on a scale | Standard Error 1.2 |
| Fesoterodine | Change in Overactive Bladder Questionnaire (OAB-q) at Week 12 Relative to Baseline - Health Related Quality of Life (HRQL) Subscales | HRQL sleep domain (n=383; n=372) | 25.9 scores on a scale | Standard Error 1.2 |
| Fesoterodine | Change in Overactive Bladder Questionnaire (OAB-q) at Week 12 Relative to Baseline - Health Related Quality of Life (HRQL) Subscales | HRQL social interaction domain (n=380; n=372) | 15.3 scores on a scale | Standard Error 0.8 |
Comparison: Week 12 minus Baseline~Concern domainp-value: <0.000195% CI: [5.3, 11.5]ANCOVA
Comparison: Week 12 minus Baseline~Coping domainp-value: <0.000195% CI: [3.9, 10.2]ANCOVA
Comparison: Week 12 minus Baseline~Sleep domainp-value: 0.003695% CI: [1.5, 7.8]ANCOVA
Comparison: Week 12 minus Baseline~Social interaction domainp-value: 0.000795% CI: [1.6, 5.8]ANCOVA
Comparison: Week 12 minus Baseline~HRQL scale score totalp-value: <0.000195% CI: [3.6, 8.9]ANCOVA
Secondary
Change in Overactive Bladder Questionnaire (OAB-q) at Week 12 Relative to Baseline - Symptom Bother Scale
Each item rated by subject on a Likert scale 1 (least symptom bother) to 6 (most symptom bother). Raw scores were transformed to a score from 0 to 100. Once transformed a negative change indicates improvement. Change: mean at Week 12 minus mean at baseline
Time frame: Baseline and Week 12
Population: Participants in the Full Analysis Set (FAS) with non-missing numerical change from baseline to Week 12.~The FAS included all participants who took at least 1 dose of assigned study drug and had at least 1 valid efficacy assessment, either at baseline or post baseline
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Overactive Bladder Questionnaire (OAB-q) at Week 12 Relative to Baseline - Symptom Bother Scale | -20.0 scores on a scale | Standard Error 1.1 |
| Fesoterodine | Change in Overactive Bladder Questionnaire (OAB-q) at Week 12 Relative to Baseline - Symptom Bother Scale | -27.8 scores on a scale | Standard Error 1.1 |
Comparison: Week 12 minus Baselinep-value: <0.000195% CI: [-10.7, -4.9]ANCOVA
Secondary
Change in Urgency Severity Visual Analog Scale (VAS) Relative to Baseline
The urgency severity VAS Scale records the subject's assessment of the severity of urgency. VAS scale ranges from 1 'Very Mild' to 10 'Very Severe'. Negative change indicated improvement. Change: mean at observation minus mean at baseline.
Time frame: Baseline, Week 2, Week 6 and Week 12
Population: Participants in the Full Analysis Set (FAS) with non-missing numerical change from baseline to Week 2, Week 6 or Week 12 (last observation carried forward \[LOCF\]).~Number analyzed=participants at Week 12 LOCF
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Urgency Severity Visual Analog Scale (VAS) Relative to Baseline | Week 2 (n=441; n=432) | -0.8 scores on a scale | Standard Error 0.1 |
| Placebo | Change in Urgency Severity Visual Analog Scale (VAS) Relative to Baseline | Week 6 (n=443; n=434) | -1.4 scores on a scale | Standard Error 0.1 |
| Placebo | Change in Urgency Severity Visual Analog Scale (VAS) Relative to Baseline | Week 12 (n=443; n=434) | -1.4 scores on a scale | Standard Error 0.1 |
| Fesoterodine | Change in Urgency Severity Visual Analog Scale (VAS) Relative to Baseline | Week 2 (n=441; n=432) | -1.4 scores on a scale | Standard Error 0.1 |
| Fesoterodine | Change in Urgency Severity Visual Analog Scale (VAS) Relative to Baseline | Week 6 (n=443; n=434) | -2.2 scores on a scale | Standard Error 0.1 |
| Fesoterodine | Change in Urgency Severity Visual Analog Scale (VAS) Relative to Baseline | Week 12 (n=443; n=434) | -2.4 scores on a scale | Standard Error 0.1 |
Comparison: Week 2 minus Baselinep-value: <0.000195% CI: [-0.9, -0.4]ANCOVA
Comparison: Week 6 minus Baselinep-value: <0.000195% CI: [-1.1, -0.5]ANCOVA
Comparison: Week 12 minus Baselinep-value: <0.000195% CI: [-1.3, -0.7]ANCOVA