Overactive Bladder
Conditions
Brief summary
To evaluate the efficacy and safety of fesoterodine in comparison to tolterodine and placebo for overactive bladder
Interventions
4 mg once daily (OD) for 1 week followed by a forced dose-escalation to 8 mg once daily (OD) for 11 weeks
DRUGplacebo
once daily (OD)for 12 weeks
4 mg once daily (OD) for 12 weeks
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult overactive bladder (OAB) patients who present with OAB symptoms, including urinary frequency \>= 8 per day and urgency urinary incontinence \>=1 per day
Exclusion criteria
* Patients with conditions that would contraindicate for fesoterodine use, e.g, hypersensitivity to the active substance (fesoterodine) or to peanut or soya or any of the excipients, urinary retention, and gastric retention. * Patients with significant hepatic and renal disease or other significant unstable diseases. * OAB symptoms caused by neurological conditions, known pathologies of urinary tract, etc.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Number of Urgency Urinary Incontinence (UUI) Episodes Per 24 Hours at Week 12 (End of Treatment). | Baseline, Week 12 | UUI per 24 hours: total number of micturitions with Urinary Sensation Scale (USS) of 5 divided by total number of diary days collected at visit. USS: 5-item scale to measure urinary urgency; range: 1 (no feeling of urgency) to 5 (unable to hold; leak urine). Change: mean at observation minus mean at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline of UUI Episodes Per 24 Hours. | Baseline, Week 1, Week 4, Week 12 | UUI episodes per 24 hours calculated as total number of micturitions with USS of 5 in diary. USS is 5-item scale measuring urinary urgency; range is 1 (no feeling of urgency) to 5 (unable to hold; leak urine). Change calculated as UUI episodes per 24 hours at observation divided by baseline number of UUI episodes per 24 hours, multiplied by 100. |
| Change From Baseline in Mean Voided Volume Per Micturition. | Baseline, Week 1, Week 4, Week 12 | Mean voided volume calculated as sum of voided volume divided by the total number of micturition episodes with a recorded voided volume greater than 0 in the 3-day diary at that visit. |
| Change From Baseline in Mean Number of Micturitions Per 24 Hours. | Baseline, Week 1, Week 4, Week 12 | The mean number of micturitions was calculated as the sum of all micturitions divided by the total number of diary days collected at that visit. Change calculated as mean at observation minus mean at baseline. |
| Percent Change From Baseline of Micturitions Per 24 Hours. | Baseline, Week 1, Week 4, Week 12 | Percent change of micturitions per 24 hours was calculated as change in 24-hour mean at that visit divided by the baseline 24-hour mean multiplied by 100 (ie, 100% \*(Week 12 or 4 - baseline)/baseline). |
| Change From Baseline in Mean Number of Nocturnal Micturitions Per 24 Hours. | Baseline, Week 1, Week 4, Week 12 | Mean number of nocturnal micturitions per 24 hours was calculated as the sum of all micturitions divided by the total number of diary days collected at that visit. Nocturnal (Bedtime) was defined as the time the subject went to bed until he/she arose to start the next day. |
| Percent Change From Baseline of Nocturnal Micturitions Per 24 Hours. | Baseline, Week 1, Week 4, Week 12 | Percent change of nocturnal micturitions per 24 hours was calculated as change in 24-hour mean at that visit divided by the baseline 24-hour mean multiplied by 100 (ie, 100% \*(Week 12 or 4 - baseline)/baseline). Nocturnal (Bedtime) was defined as the time the subject went to bed until he/she arose to start the next day. |
| Change From Baseline in Mean Number of Urgency Episodes Per 24 Hours. | Baseline, Week 1, Week 4, Week 12 | Mean number urgency episodes (USS rating \>= to 3 in diary) per 24 hours calculated as sum of all micturitions divided by total number of diary days collected at visit. USS: 5-item scale measuring urinary urgency; range is 1 (no feeling of urgency) to 5 (unable to hold; leak urine). Change calculated as mean at observation minus mean at baseline. |
| Percent Change From Baseline of Urgency Episodes Per 24 Hours. | Baseline, Week 1, Week 4, Week 12 | Percent change of urgency episodes (USS rating \>= to 3 in diary) per 24 hours calculated as change in 24-hour mean at that visit divided by the baseline 24-hour mean multiplied by 100. USS: 5-item scale measuring urinary urgency; range is 1 (no feeling of urgency) to 5 (unable to hold; leak urine). |
| Change From Baseline in Mean Number of UUI Episodes Per 24 Hours at Week 1 and Week 4. | Baseline, Week 1, Week 4 | UUI episodes per 24 hours calculated as total number of micturitions with Urinary Sensation Scale (USS) of 5 divided by total number of diary days collected at visit. USS is 5-item scale measuring urinary urgency; range is 1 (no feeling of urgency) to 5 (unable to hold; leak urine). Change calculated as mean at observation minus mean at baseline. |
| Percent Change From Baseline of Severe Urgency Episodes Per 24 Hours. | Baseline, Week 1, Week 4, Week 12 | Percent change calculated as change in severe urgency episodes (USS rating \>= to 4 in diary ) per 24 hours at that visit divided by the baseline number of severe urgency episodes per 24 hours, multiplied by 100. USS is 5-item scale measuring urinary urgency; range is 1 (no feeling of urgency) to 5 (unable to hold; leak urine). |
| Change From Baseline in Mean USS Rating Per Micturition Per 24 Hours. | Baseline, Week 1, Week 4, Week 12 | Mean USS rating calculated as the sum of rating scores on USS per 24 hours divided by the mean number of micturitions per 24 hours at that visit. USS is 5-item scale measuring urinary urgency; range is 1 (no feeling of urgency) to 5 (unable to hold; leak urine). Change calculated as mean at observation minus mean at baseline. |
| Change From Baseline in Frequency-Urgency Sum (Formerly Known as Urinary Sensations Scale Sum in Protocol) Per 24 Hours. | Baseline, Week 1, Week 4, Week 12 | Frequency-Urgency Sum rating per 24 hours calculated as mean rating scores on the USS multiplied by the mean number of micturitions per 24 hours at that visit. USS is 5-item scale measuring urinary urgency; range is 1 (no feeling of urgency) to 5 (unable to hold; leak urine). Change calculated as mean at observation minus mean at baseline. |
| Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Baseline, Week 1, Week, 4, Week 12 | Number of subjects in 4-point category: \>= to 2 points improvement \[major improvement\]; 1 point improvement \[minor improvement\]; no change; deterioration, based on PPBC score (rated on 6-point scale: 1=no problems at all; 6=many severe problems). Score change: score at observation minus score at baseline; re-scaled to 4-point categorical variables. |
| Change From Baseline in Urgency Perception Scale (UPS). UPS Equals Patient Perception of Urgency Scale (PPUS) in Protocol. | Baseline, Week 1, Week 4, Week 12 | Number of subjects in 3-point category: improvement \[\>=1-point improvement\]; no change; deterioration \[\>=1-point decrease\], based on UPS score (rated on 3-point scale: 1=not able to hold urine; 3=able to finish what I am doing). Score change calculated as score at observation minus score at baseline; re-scaled to 3-point categorical variables. |
| Change From Baseline in Overactive Bladder Questionnaire (OAB-q): Symptom Bother Score at Week 12 (End of Treatment). | Baseline, Week 12 | Symptom bother score derived as sum of scores for questions 1-8; lowest possible raw score: 8; highest possible score: 48. Data analyzed based on transformation of the score to a 0 to 100 scale \[(Actual total raw score - lowest possible value of raw score)/by raw score range \* 100\]. Higher transformed scores indicative of greater symptom bother. Negative change in Symptom Bother score indicates improvement. Change calculated as score at observation minus score at baseline. |
| Change From Baseline in OAB-q: Health Related Quality of Life (HRQL) at Week 12 (End of Treatment). | Baseline, Week 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 (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. |
| Change From Baseline in Mean Number of Severe Urgency Episodes Per 24 Hours. | Baseline, Week 1, Week 4, Week 12 | Mean number of severe urgency episodes (USS rating \>= to 4 in diary ) per 24 hours: sum of all micturitions divided by total number of diary days collected at that visit. USS: 5-item scale to measure urinary urgency; range: 1 (no feeling of urgency) to 5 (unable to hold; leak urine). Change calculated as mean at observation minus mean at baseline. |
Countries
Belgium, Brazil, Canada, Chile, Colombia, Costa Rica, Czechia, Denmark, Germany, Greece, Hong Kong, Hungary, India, Italy, Malaysia, Norway, Peru, Poland, Romania, Russia, Singapore, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Ukraine, United States
Participant flow
Recruitment details
Participants with urgency incontinence Overactive Bladder (OAB) symptoms who met all entrance criteria were randomized to the double-blind treatment period.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Tablets (4 milligrams \[mg\] orally (PO) once daily (QD) for 1 week followed by a forced dose escalation to 8 mg PO QD for 11 weeks) or capsules (4 mg) PO QD for 12 weeks | 334 |
| Tolterodine ER Capsules (4 mg) PO QD for 12 weeks. Tolterodine Extended Release (ER) | 684 |
| Fesoterodine Tablets (4 mg PO QD for 1 week followed by a forced dose escalation to 8 mg PO QD for 11 weeks) | 679 |
| Total | 1,697 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-blind Treatment Period | Adverse Event | 6 | 28 | 44 |
| Double-blind Treatment Period | Death | 2 | 0 | 0 |
| Double-blind Treatment Period | Lack of Efficacy | 5 | 5 | 13 |
| Double-blind Treatment Period | Lost to Follow-up | 4 | 8 | 5 |
| Double-blind Treatment Period | Other | 7 | 7 | 12 |
| Double-blind Treatment Period | Withdrawal by Subject | 6 | 8 | 7 |
| Randomized to Double-blind Treatment | Never returned after randomization | 3 | 6 | 6 |
Baseline characteristics
| Characteristic | Placebo | Tolterodine ER | Fesoterodine | Total |
|---|---|---|---|---|
| Age, Customized 18 - 44 years | 55 participants | 103 participants | 96 participants | 254 participants |
| Age, Customized 45 - 64 years | 167 participants | 349 participants | 367 participants | 883 participants |
| Age, Customized >= 65 years | 112 participants | 232 participants | 216 participants | 560 participants |
| Sex: Female, Male Female | 269 Participants | 564 Participants | 558 Participants | 1391 Participants |
| Sex: Female, Male Male | 65 Participants | 120 Participants | 121 Participants | 306 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 76 / — | 213 / — | 290 / — |
| serious Total, serious adverse events | 8 / — | 9 / — | 15 / — |
Outcome results
Primary
Change From Baseline in Mean Number of Urgency Urinary Incontinence (UUI) Episodes Per 24 Hours at Week 12 (End of Treatment).
UUI per 24 hours: total number of micturitions with Urinary Sensation Scale (USS) of 5 divided by total number of diary days collected at visit. USS: 5-item scale to measure urinary urgency; range: 1 (no feeling of urgency) to 5 (unable to hold; leak urine). Change: mean at observation minus mean at baseline.
Time frame: Baseline, Week 12
Population: Full analysis set (FAS): took at least 1 dose of assigned treatment, contributed data to at least 1 baseline or post-baseline efficacy assessment, and excluded 107 subjects from two study sites with significant Good Clinical Practices (GCP) deviations. The decision to exclude that data was made while the study was still blinded.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Mean Number of Urgency Urinary Incontinence (UUI) Episodes Per 24 Hours at Week 12 (End of Treatment). | -1.46 number of episodes per 24 hours | Standard Error 0.1 |
| Tolterodine ER | Change From Baseline in Mean Number of Urgency Urinary Incontinence (UUI) Episodes Per 24 Hours at Week 12 (End of Treatment). | -1.61 number of episodes per 24 hours | Standard Error 0.06 |
| Fesoterodine | Change From Baseline in Mean Number of Urgency Urinary Incontinence (UUI) Episodes Per 24 Hours at Week 12 (End of Treatment). | -1.72 number of episodes per 24 hours | Standard Error 0.06 |
Comparison: Treatment Difference Fesoterodine versus (vs) placebo at Week 12. Treatment effects estimated by Winsorized means (5% of the tails were censored, ie, replaced with the value at the fifth (5th) and ninety-fifth (95th) percentile, respectively).p-value: <0.0001Van Elteren's Test
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 12. Treatment effects estimated by Winsorized means (5% of the tails were censored, ie, replaced with the value at the 5th and 95th percentile, respectively).p-value: 0.0107Van Elteren's Test
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER at Week 12. Treatment effects estimated by Winsorized means (5% of the tails were censored, ie, replaced with the value at the 5th and 95th percentile, respectively).p-value: 0.0172Van Elteren's Test
Secondary
Change From Baseline in Frequency-Urgency Sum (Formerly Known as Urinary Sensations Scale Sum in Protocol) Per 24 Hours.
Frequency-Urgency Sum rating per 24 hours calculated as mean rating scores on the USS multiplied by the mean number of micturitions per 24 hours at that visit. USS is 5-item scale measuring urinary urgency; range is 1 (no feeling of urgency) to 5 (unable to hold; leak urine). Change calculated as mean at observation minus mean at baseline.
Time frame: Baseline, Week 1, Week 4, Week 12
Population: FAS; (n)=number of subjects with non-missing numerical change from baseline to the respective post-baseline value (Week 1, Week 4 \[LOCF\], or Week 12 \[LOCF\]) for placebo, Tolterodine ER, and Fesoterodine, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Frequency-Urgency Sum (Formerly Known as Urinary Sensations Scale Sum in Protocol) Per 24 Hours. | Week 4 [LOCF] (n=311,631, 627) | -5.7 score on scale | Standard Error 0.8 |
| Placebo | Change From Baseline in Frequency-Urgency Sum (Formerly Known as Urinary Sensations Scale Sum in Protocol) Per 24 Hours. | Week 1 (n=306, 619, 621) | -2.4 score on scale | Standard Error 0.7 |
| Placebo | Change From Baseline in Frequency-Urgency Sum (Formerly Known as Urinary Sensations Scale Sum in Protocol) Per 24 Hours. | Week 12 [LOCF] (n=311, 631, 628) | -8.2 score on scale | Standard Error 0.8 |
| Tolterodine ER | Change From Baseline in Frequency-Urgency Sum (Formerly Known as Urinary Sensations Scale Sum in Protocol) Per 24 Hours. | Week 4 [LOCF] (n=311,631, 627) | -9.7 score on scale | Standard Error 0.6 |
| Tolterodine ER | Change From Baseline in Frequency-Urgency Sum (Formerly Known as Urinary Sensations Scale Sum in Protocol) Per 24 Hours. | Week 1 (n=306, 619, 621) | -5.7 score on scale | Standard Error 0.5 |
| Tolterodine ER | Change From Baseline in Frequency-Urgency Sum (Formerly Known as Urinary Sensations Scale Sum in Protocol) Per 24 Hours. | Week 12 [LOCF] (n=311, 631, 628) | -12.1 score on scale | Standard Error 0.6 |
| Fesoterodine | Change From Baseline in Frequency-Urgency Sum (Formerly Known as Urinary Sensations Scale Sum in Protocol) Per 24 Hours. | Week 1 (n=306, 619, 621) | -5.5 score on scale | Standard Error 0.5 |
| Fesoterodine | Change From Baseline in Frequency-Urgency Sum (Formerly Known as Urinary Sensations Scale Sum in Protocol) Per 24 Hours. | Week 12 [LOCF] (n=311, 631, 628) | -13.2 score on scale | Standard Error 0.6 |
| Fesoterodine | Change From Baseline in Frequency-Urgency Sum (Formerly Known as Urinary Sensations Scale Sum in Protocol) Per 24 Hours. | Week 4 [LOCF] (n=311,631, 627) | -10.5 score on scale | Standard Error 0.6 |
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 1.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo at Week 1.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER at Week 1.p-value: 0.7288ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo at Week 4.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 4.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER at Week 4.p-value: 0.2473ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo at Week 12.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 12.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER at Week 12.p-value: 0.1047ANCOVA
Secondary
Change From Baseline in Mean Number of Micturitions Per 24 Hours.
The mean number of micturitions was calculated as the sum of all micturitions divided by the total number of diary days collected at that visit. Change calculated as mean at observation minus mean at baseline.
Time frame: Baseline, Week 1, Week 4, Week 12
Population: FAS; (n)=number of subjects with non-missing numerical change from baseline to the respective post-baseline value (Week 1, Week 4 \[LOCF\], or Week 12 \[LOCF\]) for placebo, Tolterodine ER, and Fesoterodine, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean Number of Micturitions Per 24 Hours. | Week 4 [LOCF] (n= 313, 634, 627) | -1.2 number of micturitions per 24 hours | Standard Error 0.2 |
| Placebo | Change From Baseline in Mean Number of Micturitions Per 24 Hours. | Week 1 (n=307, 622, 623) | -0.5 number of micturitions per 24 hours | Standard Error 0.1 |
| Placebo | Change From Baseline in Mean Number of Micturitions Per 24 Hours. | Week 12 [LOCF] (n= 313, 634, 628) | -1.5 number of micturitions per 24 hours | Standard Error 0.2 |
| Tolterodine ER | Change From Baseline in Mean Number of Micturitions Per 24 Hours. | Week 4 [LOCF] (n= 313, 634, 627) | -1.8 number of micturitions per 24 hours | Standard Error 0.1 |
| Tolterodine ER | Change From Baseline in Mean Number of Micturitions Per 24 Hours. | Week 1 (n=307, 622, 623) | -1.0 number of micturitions per 24 hours | Standard Error 0.1 |
| Tolterodine ER | Change From Baseline in Mean Number of Micturitions Per 24 Hours. | Week 12 [LOCF] (n= 313, 634, 628) | -2.1 number of micturitions per 24 hours | Standard Error 0.1 |
| Fesoterodine | Change From Baseline in Mean Number of Micturitions Per 24 Hours. | Week 1 (n=307, 622, 623) | -1.0 number of micturitions per 24 hours | Standard Error 0.1 |
| Fesoterodine | Change From Baseline in Mean Number of Micturitions Per 24 Hours. | Week 12 [LOCF] (n= 313, 634, 628) | -2.2 number of micturitions per 24 hours | Standard Error 0.1 |
| Fesoterodine | Change From Baseline in Mean Number of Micturitions Per 24 Hours. | Week 4 [LOCF] (n= 313, 634, 627) | -1.9 number of micturitions per 24 hours | Standard Error 0.1 |
Comparison: Treatment Difference Fesoterodine vs placebo at Week 1.p-value: 0.0002ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 1.p-value: 0.0006ANCOVA
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER at Week 1.p-value: 0.7395ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo at Week 4.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 4.p-value: 0.0007ANCOVA
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER at Week 4.p-value: 0.4185ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo at Week 12.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 12.p-value: 0.0005ANCOVA
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER at Week 12.p-value: 0.3798ANCOVA
Secondary
Change From Baseline in Mean Number of Nocturnal Micturitions Per 24 Hours.
Mean number of nocturnal micturitions per 24 hours was calculated as the sum of all micturitions divided by the total number of diary days collected at that visit. Nocturnal (Bedtime) was defined as the time the subject went to bed until he/she arose to start the next day.
Time frame: Baseline, Week 1, Week 4, Week 12
Population: FAS; Subjects reporting this symptom at baseline; (n)=number of subjects with baseline nocturnal micturitions \>0 per 24 hours, non-missing change from baseline to the respective post-baseline value (Week 1, Week 4 \[LOCF\], or Week 12 \[LOCF\]) for placebo, Tolterodine ER, and Fesoterodine, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean Number of Nocturnal Micturitions Per 24 Hours. | Week 4 [LOCF] (n=293, 596, 600) | -0.4 nocturnal micturitions per 24 hours | Standard Error 0.1 |
| Placebo | Change From Baseline in Mean Number of Nocturnal Micturitions Per 24 Hours. | Week 1 (n=288, 584, 596) | -0.1 nocturnal micturitions per 24 hours | Standard Error 0.1 |
| Placebo | Change From Baseline in Mean Number of Nocturnal Micturitions Per 24 Hours. | Week 12 [LOCF] (n=293, 596, 601) | -0.5 nocturnal micturitions per 24 hours | Standard Error 0.1 |
| Tolterodine ER | Change From Baseline in Mean Number of Nocturnal Micturitions Per 24 Hours. | Week 4 [LOCF] (n=293, 596, 600) | -0.5 nocturnal micturitions per 24 hours | Standard Error 0 |
| Tolterodine ER | Change From Baseline in Mean Number of Nocturnal Micturitions Per 24 Hours. | Week 1 (n=288, 584, 596) | -0.3 nocturnal micturitions per 24 hours | Standard Error 0 |
| Tolterodine ER | Change From Baseline in Mean Number of Nocturnal Micturitions Per 24 Hours. | Week 12 [LOCF] (n=293, 596, 601) | -0.6 nocturnal micturitions per 24 hours | Standard Error 0.1 |
| Fesoterodine | Change From Baseline in Mean Number of Nocturnal Micturitions Per 24 Hours. | Week 1 (n=288, 584, 596) | -0.2 nocturnal micturitions per 24 hours | Standard Error 0 |
| Fesoterodine | Change From Baseline in Mean Number of Nocturnal Micturitions Per 24 Hours. | Week 12 [LOCF] (n=293, 596, 601) | -0.6 nocturnal micturitions per 24 hours | Standard Error 0.1 |
| Fesoterodine | Change From Baseline in Mean Number of Nocturnal Micturitions Per 24 Hours. | Week 4 [LOCF] (n=293, 596, 600) | -0.5 nocturnal micturitions per 24 hours | Standard Error 0.1 |
Comparison: Treatment Difference Fesoterodine vs placebo at Week 1.p-value: 0.273ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 1.p-value: 0.0652ANCOVA
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER at Week 1.p-value: 0.3503ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo at Week 4.p-value: 0.2667ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 4.p-value: 0.1643ANCOVA
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER at Week 4.p-value: 0.7264ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo at Week 12.p-value: 0.3269ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 12.p-value: 0.5059ANCOVA
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER at Week 12.p-value: 0.699ANCOVA
Secondary
Change From Baseline in Mean Number of Severe Urgency Episodes Per 24 Hours.
Mean number of severe urgency episodes (USS rating \>= to 4 in diary ) per 24 hours: sum of all micturitions divided by total number of diary days collected at that visit. USS: 5-item scale to measure urinary urgency; range: 1 (no feeling of urgency) to 5 (unable to hold; leak urine). Change calculated as mean at observation minus mean at baseline.
Time frame: Baseline, Week 1, Week 4, Week 12
Population: FAS; Subjects reporting this symptom at baseline; (n)=number of subjects with baseline severe urgency episodes \>0 per 24 hours, non-missing change from baseline to the respective post-baseline value (Week 1, Week 4 \[LOCF\], or Week 12 \[LOCF\]) for placebo, Tolterodine ER, and Fesoterodine, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean Number of Severe Urgency Episodes Per 24 Hours. | Week 4 [LOCF] (n=311, 630, 624) | -1.2 severe urgency episodes per 24 hours | Standard Error 0.2 |
| Placebo | Change From Baseline in Mean Number of Severe Urgency Episodes Per 24 Hours. | Week 1 (n=306, 618, 618) | -0.4 severe urgency episodes per 24 hours | Standard Error 0.2 |
| Placebo | Change From Baseline in Mean Number of Severe Urgency Episodes Per 24 Hours. | Week 12 [LOCF] (n=311, 630, 625) | -1.9 severe urgency episodes per 24 hours | Standard Error 0.2 |
| Tolterodine ER | Change From Baseline in Mean Number of Severe Urgency Episodes Per 24 Hours. | Week 4 [LOCF] (n=311, 630, 624) | -2.2 severe urgency episodes per 24 hours | Standard Error 0.2 |
| Tolterodine ER | Change From Baseline in Mean Number of Severe Urgency Episodes Per 24 Hours. | Week 1 (n=306, 618, 618) | -1.3 severe urgency episodes per 24 hours | Standard Error 0.2 |
| Tolterodine ER | Change From Baseline in Mean Number of Severe Urgency Episodes Per 24 Hours. | Week 12 [LOCF] (n=311, 630, 625) | -2.8 severe urgency episodes per 24 hours | Standard Error 0.2 |
| Fesoterodine | Change From Baseline in Mean Number of Severe Urgency Episodes Per 24 Hours. | Week 1 (n=306, 618, 618) | -1.2 severe urgency episodes per 24 hours | Standard Error 0.2 |
| Fesoterodine | Change From Baseline in Mean Number of Severe Urgency Episodes Per 24 Hours. | Week 12 [LOCF] (n=311, 630, 625) | -3.0 severe urgency episodes per 24 hours | Standard Error 0.2 |
| Fesoterodine | Change From Baseline in Mean Number of Severe Urgency Episodes Per 24 Hours. | Week 4 [LOCF] (n=311, 630, 624) | -2.4 severe urgency episodes per 24 hours | Standard Error 0.2 |
Comparison: Treatment Difference Fesoterodine vs placebo at Week 1.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 1.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER at Week 1.p-value: 0.5581ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo at Week 4.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 4.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER at Week 4.p-value: 0.151ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo at Week 12.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 12.p-value: 0.0001ANCOVA
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER at Week 12.p-value: 0.1391ANCOVA
Secondary
Change From Baseline in Mean Number of Urgency Episodes Per 24 Hours.
Mean number urgency episodes (USS rating \>= to 3 in diary) per 24 hours calculated as sum of all micturitions divided by total number of diary days collected at visit. USS: 5-item scale measuring urinary urgency; range is 1 (no feeling of urgency) to 5 (unable to hold; leak urine). Change calculated as mean at observation minus mean at baseline.
Time frame: Baseline, Week 1, Week 4, Week 12
Population: FAS; Subjects reporting this symptom at baseline; (n)=number of subjects with baseline urgency episodes \>0 per 24 hours, non-missing change from baseline to the respective post-baseline value (Week 1, Week 4 \[LOCF\], or Week 12 \[LOCF\]) for placebo, Tolterodine ER, and Fesoterodine, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean Number of Urgency Episodes Per 24 Hours. | Week 4 [LOCF] (n=311, 631, 627) | -1.2 urgency episodes per 24 hours | Standard Error 0.2 |
| Placebo | Change From Baseline in Mean Number of Urgency Episodes Per 24 Hours. | Week 1 (n=306, 619, 621) | -0.4 urgency episodes per 24 hours | Standard Error 0.2 |
| Placebo | Change From Baseline in Mean Number of Urgency Episodes Per 24 Hours. | Week 12 [LOCF] (n=311, 631, 628) | -2.0 urgency episodes per 24 hours | Standard Error 0.3 |
| Tolterodine ER | Change From Baseline in Mean Number of Urgency Episodes Per 24 Hours. | Week 4 [LOCF] (n=311, 631, 627) | -2.4 urgency episodes per 24 hours | Standard Error 0.2 |
| Tolterodine ER | Change From Baseline in Mean Number of Urgency Episodes Per 24 Hours. | Week 1 (n=306, 619, 621) | -1.3 urgency episodes per 24 hours | Standard Error 0.2 |
| Tolterodine ER | Change From Baseline in Mean Number of Urgency Episodes Per 24 Hours. | Week 12 [LOCF] (n=311, 631, 628) | -3.1 urgency episodes per 24 hours | Standard Error 0.2 |
| Fesoterodine | Change From Baseline in Mean Number of Urgency Episodes Per 24 Hours. | Week 1 (n=306, 619, 621) | -1.1 urgency episodes per 24 hours | Standard Error 0.2 |
| Fesoterodine | Change From Baseline in Mean Number of Urgency Episodes Per 24 Hours. | Week 12 [LOCF] (n=311, 631, 628) | -3.5 urgency episodes per 24 hours | Standard Error 0.2 |
| Fesoterodine | Change From Baseline in Mean Number of Urgency Episodes Per 24 Hours. | Week 4 [LOCF] (n=311, 631, 627) | -2.6 urgency episodes per 24 hours | Standard Error 0.2 |
Comparison: Treatment Difference Fesoterodine vs placebo at Week 1.p-value: 0.0008ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 1.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER at Week 1.p-value: 0.382ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo at Week 4.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 4.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER at Week 4.p-value: 0.3498ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo at Week 12.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 12.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER at Week 12.p-value: 0.0542ANCOVA
Secondary
Change From Baseline in Mean Number of UUI Episodes Per 24 Hours at Week 1 and Week 4.
UUI episodes per 24 hours calculated as total number of micturitions with Urinary Sensation Scale (USS) of 5 divided by total number of diary days collected at visit. USS is 5-item scale measuring urinary urgency; range is 1 (no feeling of urgency) to 5 (unable to hold; leak urine). Change calculated as mean at observation minus mean at baseline.
Time frame: Baseline, Week 1, Week 4
Population: FAS; Subjects reporting this symptom at baseline; (n)=number of subjects with baseline UUI\>0 per 24 hours, non-missing change from baseline to respective post-baseline value (Week 1 or Week 4 \[Last Observation Carried Forward (LOCF)\]) for placebo, Tolterodine ER, and Fesoterodine, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean Number of UUI Episodes Per 24 Hours at Week 1 and Week 4. | Week 1 (n=302, 614, 612) | -0.54 number of episodes per 24 hours | Standard Error 0.09 |
| Placebo | Change From Baseline in Mean Number of UUI Episodes Per 24 Hours at Week 1 and Week 4. | Week 4 [LOCF] (n=307, 626, 618) | -1.06 number of episodes per 24 hours | Standard Error 0.1 |
| Tolterodine ER | Change From Baseline in Mean Number of UUI Episodes Per 24 Hours at Week 1 and Week 4. | Week 1 (n=302, 614, 612) | -0.92 number of episodes per 24 hours | Standard Error 0.06 |
| Tolterodine ER | Change From Baseline in Mean Number of UUI Episodes Per 24 Hours at Week 1 and Week 4. | Week 4 [LOCF] (n=307, 626, 618) | -1.40 number of episodes per 24 hours | Standard Error 0.06 |
| Fesoterodine | Change From Baseline in Mean Number of UUI Episodes Per 24 Hours at Week 1 and Week 4. | Week 1 (n=302, 614, 612) | -0.95 number of episodes per 24 hours | Standard Error 0.06 |
| Fesoterodine | Change From Baseline in Mean Number of UUI Episodes Per 24 Hours at Week 1 and Week 4. | Week 4 [LOCF] (n=307, 626, 618) | -1.52 number of episodes per 24 hours | Standard Error 0.06 |
Comparison: Treatment Difference Fesoterodine vs placebo at Week 1. Winsorized means (5% of the tails were censored, ie, replaced with the value at the 5th and 95th percentile, respectively).p-value: <0.0001Van Elteren's Test
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 1. Winsorized means (5% of the tails were censored, ie, replaced with the value at the 5th and 95th percentile, respectively).p-value: <0.0001Van Elteren's Test
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER at Week 1. Winsorized means (5% of the tails were censored, ie, replaced with the value at the 5th and 95th percentile, respectively).p-value: 0.846Van Elteren's Test
Comparison: Treatment Difference Fesoterodine vs placebo at Week 4. Winsorized means (5% of the tails were censored, ie, replaced with the value at the 5th and 95th percentile, respectively).p-value: <0.0001Van Elteren's Test
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 4. Winsorized means (5% of the tails were censored, ie, replaced with the value at the 5th and 95th percentile, respectively).p-value: <0.0001Van Elteren's Test
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER at Week 4. Winsorized means (5% of the tails were censored, ie, replaced with the value at the 5th and 95th percentile, respectively).p-value: 0.1937Van Elteren's Test
Secondary
Change From Baseline in Mean USS Rating Per Micturition Per 24 Hours.
Mean USS rating calculated as the sum of rating scores on USS per 24 hours divided by the mean number of micturitions per 24 hours at that visit. USS is 5-item scale measuring urinary urgency; range is 1 (no feeling of urgency) to 5 (unable to hold; leak urine). Change calculated as mean at observation minus mean at baseline.
Time frame: Baseline, Week 1, Week 4, Week 12
Population: FAS; (n)=number of subjects with non-missing numerical change from baseline to the respective post-baseline value (Week 1, Week 4 \[LOCF\], or Week 12 \[LOCF\]) for placebo, Tolterodine ER, and Fesoterodine, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean USS Rating Per Micturition Per 24 Hours. | Week 4 [LOCF] (n=311, 631, 627) | -0.2 score on scale | Standard Error 0 |
| Placebo | Change From Baseline in Mean USS Rating Per Micturition Per 24 Hours. | Week 1 (n=306, 619, 621) | -0.1 score on scale | Standard Error 0 |
| Placebo | Change From Baseline in Mean USS Rating Per Micturition Per 24 Hours. | Week 12 [LOCF] (n=311, 631, 628) | -0.4 score on scale | Standard Error 0 |
| Tolterodine ER | Change From Baseline in Mean USS Rating Per Micturition Per 24 Hours. | Week 4 [LOCF] (n=311, 631, 627) | -0.4 score on scale | Standard Error 0 |
| Tolterodine ER | Change From Baseline in Mean USS Rating Per Micturition Per 24 Hours. | Week 1 (n=306, 619, 621) | -0.2 score on scale | Standard Error 0 |
| Tolterodine ER | Change From Baseline in Mean USS Rating Per Micturition Per 24 Hours. | Week 12 [LOCF] (n=311, 631, 628) | -0.6 score on scale | Standard Error 0 |
| Fesoterodine | Change From Baseline in Mean USS Rating Per Micturition Per 24 Hours. | Week 1 (n=306, 619, 621) | -0.2 score on scale | Standard Error 0 |
| Fesoterodine | Change From Baseline in Mean USS Rating Per Micturition Per 24 Hours. | Week 12 [LOCF] (n=311, 631, 628) | -0.7 score on scale | Standard Error 0 |
| Fesoterodine | Change From Baseline in Mean USS Rating Per Micturition Per 24 Hours. | Week 4 [LOCF] (n=311, 631, 627) | -0.5 score on scale | Standard Error 0 |
Comparison: Treatment Difference Fesoterodine vs placebo at Week 1.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 1.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER at Week 1.p-value: 0.5972ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo at Week 4.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 4.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER at Week 4.p-value: 0.1267ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo at Week 12.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 12.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER at Week 12.p-value: 0.0289ANCOVA
Secondary
Change From Baseline in Mean Voided Volume Per Micturition.
Mean voided volume calculated as sum of voided volume divided by the total number of micturition episodes with a recorded voided volume greater than 0 in the 3-day diary at that visit.
Time frame: Baseline, Week 1, Week 4, Week 12
Population: FAS; (n)=number of subjects with non-missing numerical change from baseline to the respective post-baseline value (Week 1, Week 4 \[LOCF\], or Week 12 \[LOCF\]) for placebo, Tolterodine ER, and Fesoterodine, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean Voided Volume Per Micturition. | Week 12 [LOCF] (n=313, 633, 626) | 16.8 voided volume per micturition | Standard Error 3.9 |
| Placebo | Change From Baseline in Mean Voided Volume Per Micturition. | Week 4 [LOCF] (n=313, 633, 625) | 14.0 voided volume per micturition | Standard Error 3.8 |
| Placebo | Change From Baseline in Mean Voided Volume Per Micturition. | Week 1 (n=306, 622, 623) | 11.0 voided volume per micturition | Standard Error 3.2 |
| Tolterodine ER | Change From Baseline in Mean Voided Volume Per Micturition. | Week 12 [LOCF] (n=313, 633, 626) | 23.5 voided volume per micturition | Standard Error 3 |
| Tolterodine ER | Change From Baseline in Mean Voided Volume Per Micturition. | Week 1 (n=306, 622, 623) | 19.2 voided volume per micturition | Standard Error 2.5 |
| Tolterodine ER | Change From Baseline in Mean Voided Volume Per Micturition. | Week 4 [LOCF] (n=313, 633, 625) | 25.7 voided volume per micturition | Standard Error 3 |
| Fesoterodine | Change From Baseline in Mean Voided Volume Per Micturition. | Week 12 [LOCF] (n=313, 633, 626) | 32.9 voided volume per micturition | Standard Error 3.1 |
| Fesoterodine | Change From Baseline in Mean Voided Volume Per Micturition. | Week 4 [LOCF] (n=313, 633, 625) | 30.5 voided volume per micturition | Standard Error 3 |
| Fesoterodine | Change From Baseline in Mean Voided Volume Per Micturition. | Week 1 (n=306, 622, 623) | 18.7 voided volume per micturition | Standard Error 2.5 |
Comparison: Treatment Difference Fesoterodine vs placebo at Week 1.p-value: 0.0214ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 1.p-value: 0.0149ANCOVA
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER at Week 1.p-value: 0.8659ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo at Week 4.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 4.p-value: 0.0036ANCOVA
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER at Week 4.p-value: 0.1484ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo at Week 12.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 12.p-value: 0.1029ANCOVA
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER at Week 12.p-value: 0.0048ANCOVA
Secondary
Change From Baseline in OAB-q: Health Related Quality of Life (HRQL) at Week 12 (End of Treatment).
HRQL domain and total raw score derived as sum of scores (6-point scale: 1=not at all/none of the time; 6=a very great deal/all of the time). Transformed score (Total HRQL or domain)=\[(Highest possible raw score-Actual total raw score)/Raw score range\]x100. Higher transformed scores indicative of better HRQL. Positive change in HRQL scores indicates improvement. Change: score at observation minus score at baseline.
Time frame: Baseline, Week 12
Population: FAS; (n)=number of subjects with non-missing numerical change from baseline to Week 12 for placebo, Tolterodine ER, and Fesoterodine, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in OAB-q: Health Related Quality of Life (HRQL) at Week 12 (End of Treatment). | HRQL social interaction domain (n=289, 588, 572) | 6.8 score on scale | Standard Error 1.1 |
| Placebo | Change From Baseline in OAB-q: Health Related Quality of Life (HRQL) at Week 12 (End of Treatment). | HRQL sleep domain (n=289, 589, 572) | 12.2 score on scale | Standard Error 1.4 |
| Placebo | Change From Baseline in OAB-q: Health Related Quality of Life (HRQL) at Week 12 (End of Treatment). | HRQL concern domain (n=289, 589, 572) | 13.4 score on scale | Standard Error 1.5 |
| Placebo | Change From Baseline in OAB-q: Health Related Quality of Life (HRQL) at Week 12 (End of Treatment). | HRQL coping domain (n=289, 589, 572) | 14.0 score on scale | Standard Error 1.5 |
| Placebo | Change From Baseline in OAB-q: Health Related Quality of Life (HRQL) at Week 12 (End of Treatment). | HRQL scale score total (n=289, 588, 572) | 12.0 score on scale | Standard Error 1.3 |
| Tolterodine ER | Change From Baseline in OAB-q: Health Related Quality of Life (HRQL) at Week 12 (End of Treatment). | HRQL sleep domain (n=289, 589, 572) | 15.1 score on scale | Standard Error 1.1 |
| Tolterodine ER | Change From Baseline in OAB-q: Health Related Quality of Life (HRQL) at Week 12 (End of Treatment). | HRQL concern domain (n=289, 589, 572) | 19.3 score on scale | Standard Error 1.1 |
| Tolterodine ER | Change From Baseline in OAB-q: Health Related Quality of Life (HRQL) at Week 12 (End of Treatment). | HRQL coping domain (n=289, 589, 572) | 18.5 score on scale | Standard Error 1.2 |
| Tolterodine ER | Change From Baseline in OAB-q: Health Related Quality of Life (HRQL) at Week 12 (End of Treatment). | HRQL social interaction domain (n=289, 588, 572) | 9.4 score on scale | Standard Error 0.9 |
| Tolterodine ER | Change From Baseline in OAB-q: Health Related Quality of Life (HRQL) at Week 12 (End of Treatment). | HRQL scale score total (n=289, 588, 572) | 16.3 score on scale | Standard Error 1 |
| Fesoterodine | Change From Baseline in OAB-q: Health Related Quality of Life (HRQL) at Week 12 (End of Treatment). | HRQL scale score total (n=289, 588, 572) | 19.3 score on scale | Standard Error 1 |
| Fesoterodine | Change From Baseline in OAB-q: Health Related Quality of Life (HRQL) at Week 12 (End of Treatment). | HRQL social interaction domain (n=289, 588, 572) | 11.6 score on scale | Standard Error 0.9 |
| Fesoterodine | Change From Baseline in OAB-q: Health Related Quality of Life (HRQL) at Week 12 (End of Treatment). | HRQL concern domain (n=289, 589, 572) | 22.6 score on scale | Standard Error 1.2 |
| Fesoterodine | Change From Baseline in OAB-q: Health Related Quality of Life (HRQL) at Week 12 (End of Treatment). | HRQL sleep domain (n=289, 589, 572) | 17.3 score on scale | Standard Error 1.1 |
| Fesoterodine | Change From Baseline in OAB-q: Health Related Quality of Life (HRQL) at Week 12 (End of Treatment). | HRQL coping domain (n=289, 589, 572) | 22.6 score on scale | Standard Error 1.2 |
Comparison: Treatment Difference Fesoterodine vs placebo: HRQL concern domain.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo: HRQL coping domain.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo: HRQL sleep domain.p-value: 0.0008ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo: HRQL social interaction domain.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo: HRQL scale score total.p-value: <0.0001ANCOVA
Secondary
Change From Baseline in Overactive Bladder Questionnaire (OAB-q): Symptom Bother Score at Week 12 (End of Treatment).
Symptom bother score derived as sum of scores for questions 1-8; lowest possible raw score: 8; highest possible score: 48. Data analyzed based on transformation of the score to a 0 to 100 scale \[(Actual total raw score - lowest possible value of raw score)/by raw score range \* 100\]. Higher transformed scores indicative of greater symptom bother. Negative change in Symptom Bother score indicates improvement. Change calculated as score at observation minus score at baseline.
Time frame: Baseline, Week 12
Population: FAS; (n)=number of subjects with non-missing numerical change from baseline to Week 12 for placebo n=289; Tolterodine ER n=589; Fesoterodine n=571.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Overactive Bladder Questionnaire (OAB-q): Symptom Bother Score at Week 12 (End of Treatment). | -16.3 score on scale | Standard Error 1.4 |
| Tolterodine ER | Change From Baseline in Overactive Bladder Questionnaire (OAB-q): Symptom Bother Score at Week 12 (End of Treatment). | -22.5 score on scale | Standard Error 1.1 |
| Fesoterodine | Change From Baseline in Overactive Bladder Questionnaire (OAB-q): Symptom Bother Score at Week 12 (End of Treatment). | -27.1 score on scale | Standard Error 1.1 |
Comparison: Treatment difference Fesoterodine vs placebo at Week 12p-value: <0.0001ANCOVA
Secondary
Change From Baseline in Patient Perception of Bladder Condition (PPBC).
Number of subjects in 4-point category: \>= to 2 points improvement \[major improvement\]; 1 point improvement \[minor improvement\]; no change; deterioration, based on PPBC score (rated on 6-point scale: 1=no problems at all; 6=many severe problems). Score change: score at observation minus score at baseline; re-scaled to 4-point categorical variables.
Time frame: Baseline, Week 1, Week, 4, Week 12
Population: FAS; (n)=number of subjects with non-missing numerical change from baseline to the respective post-baseline value (Week 1, Week 4 \[LOCF\], or Week 12 \[LOCF\]) for placebo, Tolterodine ER, and Fesoterodine, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 12, no change | 111 participants |
| Placebo | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 1 (n=309, 625, 623), >=2 points improvement | 32 participants |
| Placebo | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 4 (n=313, 632, 629), >=2 points improvement | 57 participants |
| Placebo | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 12 (n=313, 632, 630), >=2 points improvement | 67 participants |
| Placebo | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 12, 1-point improvement | 102 participants |
| Placebo | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 4, 1-point improvement | 95 participants |
| Placebo | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 12, deterioration | 33 participants |
| Placebo | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 1, 1-point improvement | 94 participants |
| Placebo | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 4, no change | 127 participants |
| Placebo | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 1, no change | 147 participants |
| Placebo | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 1, deterioration | 36 participants |
| Placebo | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 4, deterioration | 34 participants |
| Tolterodine ER | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 1, deterioration | 59 participants |
| Tolterodine ER | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 12 (n=313, 632, 630), >=2 points improvement | 210 participants |
| Tolterodine ER | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 12, 1-point improvement | 189 participants |
| Tolterodine ER | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 12, no change | 171 participants |
| Tolterodine ER | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 1, no change | 306 participants |
| Tolterodine ER | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 12, deterioration | 62 participants |
| Tolterodine ER | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 4, deterioration | 59 participants |
| Tolterodine ER | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 1 (n=309, 625, 623), >=2 points improvement | 79 participants |
| Tolterodine ER | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 4 (n=313, 632, 629), >=2 points improvement | 169 participants |
| Tolterodine ER | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 4, 1-point improvement | 201 participants |
| Tolterodine ER | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 4, no change | 203 participants |
| Tolterodine ER | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 1, 1-point improvement | 181 participants |
| Fesoterodine | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 12, deterioration | 30 participants |
| Fesoterodine | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 12 (n=313, 632, 630), >=2 points improvement | 254 participants |
| Fesoterodine | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 1 (n=309, 625, 623), >=2 points improvement | 102 participants |
| Fesoterodine | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 1, 1-point improvement | 186 participants |
| Fesoterodine | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 1, deterioration | 49 participants |
| Fesoterodine | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 4 (n=313, 632, 629), >=2 points improvement | 196 participants |
| Fesoterodine | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 4, 1-point improvement | 224 participants |
| Fesoterodine | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 4, no change | 176 participants |
| Fesoterodine | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 4, deterioration | 33 participants |
| Fesoterodine | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 12, 1-point improvement | 198 participants |
| Fesoterodine | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 12, no change | 148 participants |
| Fesoterodine | Change From Baseline in Patient Perception of Bladder Condition (PPBC). | Week 1, no change | 286 participants |
Comparison: Fesoterodine vs placebo at Week 1p-value: 0.0143Cochran-Mantel-Haenszel
Comparison: Fesoterodine vs placebo at Week 4p-value: <0.0001Cochran-Mantel-Haenszel
Comparison: Fesoterodine vs placebo at Week 12p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Urgency Perception Scale (UPS). UPS Equals Patient Perception of Urgency Scale (PPUS) in Protocol.
Number of subjects in 3-point category: improvement \[\>=1-point improvement\]; no change; deterioration \[\>=1-point decrease\], based on UPS score (rated on 3-point scale: 1=not able to hold urine; 3=able to finish what I am doing). Score change calculated as score at observation minus score at baseline; re-scaled to 3-point categorical variables.
Time frame: Baseline, Week 1, Week 4, Week 12
Population: FAS; (n)=number of subjects with non-missing numerical change from baseline to the respective post-baseline value (Week 1, Week 4 \[LOCF\], or Week 12 \[LOCF\]) for placebo, Tolterodine ER, and Fesoterodine, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Change From Baseline in Urgency Perception Scale (UPS). UPS Equals Patient Perception of Urgency Scale (PPUS) in Protocol. | Week 12 (n=313, 633, 630), improvement | 112 participants |
| Placebo | Change From Baseline in Urgency Perception Scale (UPS). UPS Equals Patient Perception of Urgency Scale (PPUS) in Protocol. | Week 4 (n=313, 633, 629), improvement | 98 participants |
| Placebo | Change From Baseline in Urgency Perception Scale (UPS). UPS Equals Patient Perception of Urgency Scale (PPUS) in Protocol. | Week 1, no change | 218 participants |
| Placebo | Change From Baseline in Urgency Perception Scale (UPS). UPS Equals Patient Perception of Urgency Scale (PPUS) in Protocol. | Week 4, deterioration | 21 participants |
| Placebo | Change From Baseline in Urgency Perception Scale (UPS). UPS Equals Patient Perception of Urgency Scale (PPUS) in Protocol. | Week 4, no change | 194 participants |
| Placebo | Change From Baseline in Urgency Perception Scale (UPS). UPS Equals Patient Perception of Urgency Scale (PPUS) in Protocol. | Week 1 (n=309, 627, 624), improvement | 68 participants |
| Placebo | Change From Baseline in Urgency Perception Scale (UPS). UPS Equals Patient Perception of Urgency Scale (PPUS) in Protocol. | Week 12, no change | 181 participants |
| Placebo | Change From Baseline in Urgency Perception Scale (UPS). UPS Equals Patient Perception of Urgency Scale (PPUS) in Protocol. | Week 1, deterioration | 23 participants |
| Placebo | Change From Baseline in Urgency Perception Scale (UPS). UPS Equals Patient Perception of Urgency Scale (PPUS) in Protocol. | Week 12, deterioration | 20 participants |
| Tolterodine ER | Change From Baseline in Urgency Perception Scale (UPS). UPS Equals Patient Perception of Urgency Scale (PPUS) in Protocol. | Week 12, no change | 344 participants |
| Tolterodine ER | Change From Baseline in Urgency Perception Scale (UPS). UPS Equals Patient Perception of Urgency Scale (PPUS) in Protocol. | Week 1 (n=309, 627, 624), improvement | 162 participants |
| Tolterodine ER | Change From Baseline in Urgency Perception Scale (UPS). UPS Equals Patient Perception of Urgency Scale (PPUS) in Protocol. | Week 1, no change | 438 participants |
| Tolterodine ER | Change From Baseline in Urgency Perception Scale (UPS). UPS Equals Patient Perception of Urgency Scale (PPUS) in Protocol. | Week 1, deterioration | 27 participants |
| Tolterodine ER | Change From Baseline in Urgency Perception Scale (UPS). UPS Equals Patient Perception of Urgency Scale (PPUS) in Protocol. | Week 4 (n=313, 633, 629), improvement | 238 participants |
| Tolterodine ER | Change From Baseline in Urgency Perception Scale (UPS). UPS Equals Patient Perception of Urgency Scale (PPUS) in Protocol. | Week 4, no change | 362 participants |
| Tolterodine ER | Change From Baseline in Urgency Perception Scale (UPS). UPS Equals Patient Perception of Urgency Scale (PPUS) in Protocol. | Week 4, deterioration | 33 participants |
| Tolterodine ER | Change From Baseline in Urgency Perception Scale (UPS). UPS Equals Patient Perception of Urgency Scale (PPUS) in Protocol. | Week 12 (n=313, 633, 630), improvement | 254 participants |
| Tolterodine ER | Change From Baseline in Urgency Perception Scale (UPS). UPS Equals Patient Perception of Urgency Scale (PPUS) in Protocol. | Week 12, deterioration | 35 participants |
| Fesoterodine | Change From Baseline in Urgency Perception Scale (UPS). UPS Equals Patient Perception of Urgency Scale (PPUS) in Protocol. | Week 4, deterioration | 25 participants |
| Fesoterodine | Change From Baseline in Urgency Perception Scale (UPS). UPS Equals Patient Perception of Urgency Scale (PPUS) in Protocol. | Week 1, deterioration | 40 participants |
| Fesoterodine | Change From Baseline in Urgency Perception Scale (UPS). UPS Equals Patient Perception of Urgency Scale (PPUS) in Protocol. | Week 12, deterioration | 25 participants |
| Fesoterodine | Change From Baseline in Urgency Perception Scale (UPS). UPS Equals Patient Perception of Urgency Scale (PPUS) in Protocol. | Week 12 (n=313, 633, 630), improvement | 291 participants |
| Fesoterodine | Change From Baseline in Urgency Perception Scale (UPS). UPS Equals Patient Perception of Urgency Scale (PPUS) in Protocol. | Week 1, no change | 413 participants |
| Fesoterodine | Change From Baseline in Urgency Perception Scale (UPS). UPS Equals Patient Perception of Urgency Scale (PPUS) in Protocol. | Week 12, no change | 314 participants |
| Fesoterodine | Change From Baseline in Urgency Perception Scale (UPS). UPS Equals Patient Perception of Urgency Scale (PPUS) in Protocol. | Week 4, no change | 348 participants |
| Fesoterodine | Change From Baseline in Urgency Perception Scale (UPS). UPS Equals Patient Perception of Urgency Scale (PPUS) in Protocol. | Week 4 (n=313, 633, 629), improvement | 256 participants |
| Fesoterodine | Change From Baseline in Urgency Perception Scale (UPS). UPS Equals Patient Perception of Urgency Scale (PPUS) in Protocol. | Week 1 (n=309, 627, 624), improvement | 171 participants |
Comparison: Fesoterodine vs placebo at Week 1p-value: 0.0773Cochran-Mantel-Haenszel
Comparison: Fesoterodine vs placebo at Week 4p-value: 0.0017Cochran-Mantel-Haenszel
Comparison: Fesoterodine vs placebo at Week 12p-value: 0.0008Cochran-Mantel-Haenszel
Secondary
Percent Change From Baseline of Micturitions Per 24 Hours.
Percent change of micturitions per 24 hours was calculated as change in 24-hour mean at that visit divided by the baseline 24-hour mean multiplied by 100 (ie, 100% \*(Week 12 or 4 - baseline)/baseline).
Time frame: Baseline, Week 1, Week 4, Week 12
Population: FAS; (n)=number of subjects with non-missing percent change from baseline to the respective post-baseline value (Week 1, Week 4 \[LOCF\], or Week 12 \[LOCF\]) for placebo, Tolterodine ER, and Fesoterodine, respectively.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Percent Change From Baseline of Micturitions Per 24 Hours. | Week 4 [LOCF] (n=313, 634, 627) | -10.3 percent change |
| Placebo | Percent Change From Baseline of Micturitions Per 24 Hours. | Week 1 (n=307, 622, 623) | -2.7 percent change |
| Placebo | Percent Change From Baseline of Micturitions Per 24 Hours. | Week 12 [LOCF] (n=313, 634, 628) | -12.1 percent change |
| Tolterodine ER | Percent Change From Baseline of Micturitions Per 24 Hours. | Week 4 [LOCF] (n=313, 634, 627) | -15.0 percent change |
| Tolterodine ER | Percent Change From Baseline of Micturitions Per 24 Hours. | Week 1 (n=307, 622, 623) | -7.7 percent change |
| Tolterodine ER | Percent Change From Baseline of Micturitions Per 24 Hours. | Week 12 [LOCF] (n=313, 634, 628) | -16.2 percent change |
| Fesoterodine | Percent Change From Baseline of Micturitions Per 24 Hours. | Week 1 (n=307, 622, 623) | -7.9 percent change |
| Fesoterodine | Percent Change From Baseline of Micturitions Per 24 Hours. | Week 12 [LOCF] (n=313, 634, 628) | -18.9 percent change |
| Fesoterodine | Percent Change From Baseline of Micturitions Per 24 Hours. | Week 4 [LOCF] (n=313, 634, 627) | -14.8 percent change |
Comparison: Treatment Difference Fesoterodine vs placebo at Week 1. Per closed testing procedure, statistical testing for percent change not performed for Fesoterodine vs Tolterodine ER Week 1: corresponding numerical change result not statistically significant.p-value: 0.0001ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 1. Per closed testing procedure, statistical testing for percent change not performed for Fesoterodine vs Tolterodine ER Week 1: corresponding numerical change result not statistically significant.p-value: 0.0002ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo at Week 4. Per closed testing procedure, statistical testing for percent change not performed for Fesoterodine vs Tolterodine ER Week 4: corresponding numerical change result not statistically significant.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 4. Per closed testing procedure, statistical testing for percent change not performed for Fesoterodine vs Tolterodine ER Week 4: corresponding numerical change result not statistically significant.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo at Week 12. Per closed testing procedure, statistical testing for percent change not performed for Fesoterodine vs Tolterodine ER Week 12: corresponding numerical change result not statistically significant.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 12. Per closed testing procedure, statistical testing for percent change not performed for Fesoterodine vs Tolterodine ER Week 12: corresponding numerical change result not statistically significant.p-value: 0.0003ANCOVA
Secondary
Percent Change From Baseline of Nocturnal Micturitions Per 24 Hours.
Percent change of nocturnal micturitions per 24 hours was calculated as change in 24-hour mean at that visit divided by the baseline 24-hour mean multiplied by 100 (ie, 100% \*(Week 12 or 4 - baseline)/baseline). Nocturnal (Bedtime) was defined as the time the subject went to bed until he/she arose to start the next day.
Time frame: Baseline, Week 1, Week 4, Week 12
Population: FAS; Subjects reporting this symptom at baseline; (n)=number of subjects with baseline nocturnal micturitions \>0 per 24 hours, non-missing change from baseline to the respective post-baseline value (Week 1, Week 4 \[LOCF\], or Week 12 \[LOCF\]) for placebo, Tolterodine ER, and Fesoterodine, respectively.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Percent Change From Baseline of Nocturnal Micturitions Per 24 Hours. | Week 4 [LOCF] (n=293, 596, 600) | -22.2 percent change |
| Placebo | Percent Change From Baseline of Nocturnal Micturitions Per 24 Hours. | Week 1 (n=288, 584, 596) | -10.0 percent change |
| Placebo | Percent Change From Baseline of Nocturnal Micturitions Per 24 Hours. | Week 12 [LOCF] (n=293, 596, 601) | -25.0 percent change |
| Tolterodine ER | Percent Change From Baseline of Nocturnal Micturitions Per 24 Hours. | Week 4 [LOCF] (n=293, 596, 600) | -25.0 percent change |
| Tolterodine ER | Percent Change From Baseline of Nocturnal Micturitions Per 24 Hours. | Week 1 (n=288, 584, 596) | -12.5 percent change |
| Tolterodine ER | Percent Change From Baseline of Nocturnal Micturitions Per 24 Hours. | Week 12 [LOCF] (n=293, 596, 601) | -27.9 percent change |
| Fesoterodine | Percent Change From Baseline of Nocturnal Micturitions Per 24 Hours. | Week 1 (n=288, 584, 596) | 0.0 percent change |
| Fesoterodine | Percent Change From Baseline of Nocturnal Micturitions Per 24 Hours. | Week 12 [LOCF] (n=293, 596, 601) | -28.6 percent change |
| Fesoterodine | Percent Change From Baseline of Nocturnal Micturitions Per 24 Hours. | Week 4 [LOCF] (n=293, 596, 600) | -20.0 percent change |
Secondary
Percent Change From Baseline of Severe Urgency Episodes Per 24 Hours.
Percent change calculated as change in severe urgency episodes (USS rating \>= to 4 in diary ) per 24 hours at that visit divided by the baseline number of severe urgency episodes per 24 hours, multiplied by 100. USS is 5-item scale measuring urinary urgency; range is 1 (no feeling of urgency) to 5 (unable to hold; leak urine).
Time frame: Baseline, Week 1, Week 4, Week 12
Population: FAS; Subjects reporting this symptom at baseline; (n)=number of subjects with baseline severe urgency episodes \>0 per 24 hours, non-missing change from baseline to the respective post-baseline value (Week 1, Week 4 \[LOCF\], or Week 12 \[LOCF\]) for placebo, Tolterodine ER, and Fesoterodine, respectively.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Percent Change From Baseline of Severe Urgency Episodes Per 24 Hours. | Week 4 [LOCF] (n=311, 630, 624) | -25.0 percent change |
| Placebo | Percent Change From Baseline of Severe Urgency Episodes Per 24 Hours. | Week 1 (n=306, 618, 618) | -9.4 percent change |
| Placebo | Percent Change From Baseline of Severe Urgency Episodes Per 24 Hours. | Week 12 [LOCF] (n=311, 630, 625) | -48.0 percent change |
| Tolterodine ER | Percent Change From Baseline of Severe Urgency Episodes Per 24 Hours. | Week 4 [LOCF] (n=311, 630, 624) | -45.8 percent change |
| Tolterodine ER | Percent Change From Baseline of Severe Urgency Episodes Per 24 Hours. | Week 1 (n=306, 618, 618) | -25.0 percent change |
| Tolterodine ER | Percent Change From Baseline of Severe Urgency Episodes Per 24 Hours. | Week 12 [LOCF] (n=311, 630, 625) | -63.4 percent change |
| Fesoterodine | Percent Change From Baseline of Severe Urgency Episodes Per 24 Hours. | Week 1 (n=306, 618, 618) | -25.0 percent change |
| Fesoterodine | Percent Change From Baseline of Severe Urgency Episodes Per 24 Hours. | Week 12 [LOCF] (n=311, 630, 625) | -71.4 percent change |
| Fesoterodine | Percent Change From Baseline of Severe Urgency Episodes Per 24 Hours. | Week 4 [LOCF] (n=311, 630, 624) | -54.5 percent change |
Comparison: Treatment Difference Fesoterodine vs placebo at Week 1. Per closed testing procedure, statistical testing for percent change not performed for Fesoterodine vs Tolterodine ER Week 1: corresponding numerical change result not statistically significant.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 1. Per closed testing procedure, statistical testing for percent change not performed for Fesoterodine vs Tolterodine ER Week 1: corresponding numerical change result not statistically significant.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo at Week 4. Per closed testing procedure, statistical testing for percent change not performed for Fesoterodine vs Tolterodine ER Week 4: corresponding numerical change result not statistically significant.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 4. Per closed testing procedure, statistical testing for percent change not performed for Fesoterodine vs Tolterodine ER Week 4: corresponding numerical change result not statistically significant.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo at Week 12. Per closed testing procedure, statistical testing for percent change not performed for Fesoterodine vs Tolterodine ER Week 12: corresponding numerical change result not statistically significant.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 12. Per closed testing procedure, statistical testing for percent change not performed for Fesoterodine vs Tolterodine ER Week 12: corresponding numerical change result not statistically significant.p-value: 0.0001ANCOVA
Secondary
Percent Change From Baseline of Urgency Episodes Per 24 Hours.
Percent change of urgency episodes (USS rating \>= to 3 in diary) per 24 hours calculated as change in 24-hour mean at that visit divided by the baseline 24-hour mean multiplied by 100. USS: 5-item scale measuring urinary urgency; range is 1 (no feeling of urgency) to 5 (unable to hold; leak urine).
Time frame: Baseline, Week 1, Week 4, Week 12
Population: FAS; Subjects reporting this symptom at baseline; (n)=number of subjects with baseline urgency episodes \>0 per 24 hours, non-missing change from baseline to the respective post-baseline value (Week 1, Week 4 \[LOCF\], or Week 12 \[LOCF\]) for placebo, Tolterodine ER, and Fesoterodine, respectively.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Percent Change From Baseline of Urgency Episodes Per 24 Hours. | Week 12 [LOCF] (n=311, 631, 628) | -17.6 percent change |
| Placebo | Percent Change From Baseline of Urgency Episodes Per 24 Hours. | Week 1 (n=306, 619, 621) | -5.6 percent change |
| Placebo | Percent Change From Baseline of Urgency Episodes Per 24 Hours. | Week 4 [LOCF] (n=311,631, 627) | -11.4 percent change |
| Tolterodine ER | Percent Change From Baseline of Urgency Episodes Per 24 Hours. | Week 12 [LOCF] (n=311, 631, 628) | -30.8 percent change |
| Tolterodine ER | Percent Change From Baseline of Urgency Episodes Per 24 Hours. | Week 1 (n=306, 619, 621) | -12.5 percent change |
| Tolterodine ER | Percent Change From Baseline of Urgency Episodes Per 24 Hours. | Week 4 [LOCF] (n=311,631, 627) | -23.1 percent change |
| Fesoterodine | Percent Change From Baseline of Urgency Episodes Per 24 Hours. | Week 12 [LOCF] (n=311, 631, 628) | -37.9 percent change |
| Fesoterodine | Percent Change From Baseline of Urgency Episodes Per 24 Hours. | Week 4 [LOCF] (n=311,631, 627) | -26.9 percent change |
| Fesoterodine | Percent Change From Baseline of Urgency Episodes Per 24 Hours. | Week 1 (n=306, 619, 621) | -9.7 percent change |
Comparison: Treatment Difference Fesoterodine vs placebo at Week 1. Per closed testing procedure, statistical testing for percent change not performed for Fesoterodine vs Tolterodine ER Week 1: corresponding numerical change result not statistically significant.p-value: 0.0004ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 1. Per closed testing procedure, statistical testing for percent change not performed for Fesoterodine vs Tolterodine ER Week 1: corresponding numerical change result not statistically significant.p-value: 0.0001ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo at Week 4. Per closed testing procedure, statistical testing for percent change not performed for Fesoterodine vs Tolterodine ER Week 4: corresponding numerical change result not statistically significant.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 4. Per closed testing procedure, statistical testing for percent change not performed for Fesoterodine vs Tolterodine ER Week 4: corresponding numerical change result not statistically significant.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo at Week 12. Per closed testing procedure, statistical testing for percent change not performed for Fesoterodine vs Tolterodine ER Week 12: corresponding numerical change result not statistically significant.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 12. Per closed testing procedure, statistical testing for percent change not performed for Fesoterodine vs Tolterodine ER Week 12: corresponding numerical change result not statistically significant.p-value: 0.0001ANCOVA
Secondary
Percent Change From Baseline of UUI Episodes Per 24 Hours.
UUI episodes per 24 hours calculated as total number of micturitions with USS of 5 in diary. USS is 5-item scale measuring urinary urgency; range is 1 (no feeling of urgency) to 5 (unable to hold; leak urine). Change calculated as UUI episodes per 24 hours at observation divided by baseline number of UUI episodes per 24 hours, multiplied by 100.
Time frame: Baseline, Week 1, Week 4, Week 12
Population: FAS; Subjects reporting this symptom at baseline; (n)=number of subjects with baseline UUI\>0 per 24 hours, non-missing change from baseline to respective post-baseline value (Week 1, Week 4 \[LOCF\], or Week 12 \[LOCF\]) for placebo, Tolterodine ER, and Fesoterodine, respectively.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Percent Change From Baseline of UUI Episodes Per 24 Hours. | Week 4 [LOCF] (n=307, 626, 618) | -60.0 percent change |
| Placebo | Percent Change From Baseline of UUI Episodes Per 24 Hours. | Week 1 (n=302, 614, 612) | -28.6 percent change |
| Placebo | Percent Change From Baseline of UUI Episodes Per 24 Hours. | Week 12 [LOCF] (n=307, 626, 619) | -82.1 percent change |
| Tolterodine ER | Percent Change From Baseline of UUI Episodes Per 24 Hours. | Week 4 [LOCF] (n=307, 626, 618) | -85.7 percent change |
| Tolterodine ER | Percent Change From Baseline of UUI Episodes Per 24 Hours. | Week 1 (n=302, 614, 612) | -55.1 percent change |
| Tolterodine ER | Percent Change From Baseline of UUI Episodes Per 24 Hours. | Week 12 [LOCF] (n=307, 626, 619) | -100.0 percent change |
| Fesoterodine | Percent Change From Baseline of UUI Episodes Per 24 Hours. | Week 1 (n=302, 614, 612) | -53.6 percent change |
| Fesoterodine | Percent Change From Baseline of UUI Episodes Per 24 Hours. | Week 12 [LOCF] (n=307, 626, 619) | -100.0 percent change |
| Fesoterodine | Percent Change From Baseline of UUI Episodes Per 24 Hours. | Week 4 [LOCF] (n=307, 626, 618) | -93.2 percent change |
Comparison: Treatment Difference Fesoterodine vs placebo at Week 12.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 12.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER at Week 12.p-value: 0.022ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo at Week 1. Per closed testing procedure, statistical testing for percent change not performed for Fesoterodine vs Tolterodine ER Week 1: corresponding numerical change result not statistically significant.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 1. Per closed testing procedure, statistical testing for percent change not performed for Fesoterodine vs Tolterodine ER Week 1: corresponding numerical change result not statistically significant.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo at Week 4. Per closed testing procedure, statistical testing for percent change not performed for Fesoterodine vs Tolterodine ER Week 4: corresponding numerical change result not statistically significant.p-value: <0.0001ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 4. Per closed testing procedure, statistical testing for percent change not performed for Fesoterodine vs Tolterodine ER Week 4: corresponding numerical change result not statistically significant.p-value: <0.0001ANCOVA
Post Hoc
Diary Dry Rates
Diary dry rate: number of subjects with no urgency urinary incontinence episode reported in the 3 day diary at the respective time-point; based on USS: 5-item scale measuring urinary urgency; range is 1 (no feeling of urgency) to 5 (unable to hold; leak urine).
Time frame: Week 1, Week 4, Week 12
Population: FAS; only subjects with baseline urgency urinary incontinence \>0 per 24 hours are included; n=number of subjects in the respective category at observation (Week 1, Week 4, Week 12).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Diary Dry Rates | Week 12 | 138 participants |
| Placebo | Diary Dry Rates | Week 1 | 54 participants |
| Placebo | Diary Dry Rates | Week 4 | 97 participants |
| Tolterodine ER | Diary Dry Rates | Week 12 | 358 participants |
| Tolterodine ER | Diary Dry Rates | Week 4 | 290 participants |
| Tolterodine ER | Diary Dry Rates | Week 1 | 153 participants |
| Fesoterodine | Diary Dry Rates | Week 12 | 396 participants |
| Fesoterodine | Diary Dry Rates | Week 4 | 306 participants |
| Fesoterodine | Diary Dry Rates | Week 1 | 159 participants |
Comparison: Treatment Difference Fesoterodine vs placebo at Week 1.p-value: 0.0072Cochran-Mantel-Haenszel
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 1.p-value: 0.0116Cochran-Mantel-Haenszel
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER at Week 1.p-value: 0.7828Cochran-Mantel-Haenszel
Comparison: Treatment Difference Fesoterodine vs placebo at Week 4.p-value: <0.0001Cochran-Mantel-Haenszel
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 4.p-value: <0.0001Cochran-Mantel-Haenszel
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER at Week 4.p-value: 0.3104Cochran-Mantel-Haenszel
Comparison: Treatment Difference Fesoterodine vs placebo at Week 12.p-value: <0.0001Cochran-Mantel-Haenszel
Comparison: Treatment Difference Tolterodine ER vs placebo at Week 12.p-value: 0.0004Cochran-Mantel-Haenszel
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER at Week 12.p-value: 0.0153Cochran-Mantel-Haenszel