Overactive Bladder
Conditions
Keywords
Treatment of overactive bladder
Brief summary
To evaluate the efficacy and safety of fesoterodine in comparison to tolterodine and placebo for overactive bladder
Interventions
DRUGTolterodine ER
The tolterodine treatment will be 4 mg once daily(QD) for 12 weeks.
DRUGPlacebo
Placebo treatment will be once daily(QD) for 12 weeks.
DRUGFesoterodine
The fesoterodine treatment will start with 4 mg once daily(QD) for 1 week followed by a forced dose-escalation to 8mg once daily(QD) for 11 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 subjects with overactive bladder symptoms (subject-reported) for greater than or equal to 3 months prior to Screening/Enrollment visit. * Reported at least an average of 1 UUI episode per 24 hours in the 3-day bladder diary prior to the Randomization/Baseline visit * Mean urinary frequency of greater than or equal to 8 micturitions per 24 hours as verified by the 3-day bladder diary prior to randomization/Baseline visit.
Exclusion criteria
* Subjects with any condition that would contraindicate their usage of fesoterodine including: hypersensitivity to the active substance (fesoterodine fumarate) or to peanut or soya or any of the excipients, urinary retention, gastric retention, uncontrolled narrow angle glaucoma, myasthenia gravis, severe hepatic impairment (Child Pugh C), severe ulcerative colitis, and toxic megacolon. * Subjects with clinically significant hepatic or renal disease or other significant unstable diseases. * OAB symptoms caused by neurological conditions, known pathologies of urinary tract, etc. * Subjects with previous history of acute urinary retention requiring catheterization, or severe voiding difficulties in the judgment of the investigator, prior to baseline.
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 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 total number of micturitions divided by the total number of diary days collected at that visit. |
| 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 1 or 4 or 12 - 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 total number of all micturitions divided by the total number of diary days collected at that visit. Nocturnal micturitions are those recorded in the Bedtime section of the diary. Nocturnal (Bedtime) was defined as the time the participant 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 1 or 4 or 12 - baseline)/baseline). Nocturnal micturitions are those recorded in the Bedtime section of the diary. Nocturnal (Bedtime) was defined as the time the participant went to bed until he/she arose to start the next day. |
| Change From Baseline in Mean Number of Urgency Urinary Incontinence (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). |
| 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 Number of Urgency Urinary Episodes Per 24 Hours (Urinary Sensation Scale ≥3 in the Diary) | Baseline, Week 1, Week 4, Week 12 | Urgency Urinary episodes per 24 hours: total number of micturitions with Urinary Sensation Scale (USS) of ≥3 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). |
| Percent Change From Baseline in Mean Number of Urgency Urinary Episodes Per 24 Hours (Urinary Sensation Scale ≥3 in the Diary) | Baseline, Week 1, Week 4, Week 12 | Percent change from baseline in mean number of Urgency Urinary episodes per 24 hours (Urinary Sensation Scale ≥3 in the diary). 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 in milliliters (mL) 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. |
| 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 ≥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 Urinary Sensation Scale (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 total number of micturitions per 24 hours with non-missing rating 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 From Baseline in Frequency-Urgency Sum (FUS) Per 24 Hours (Synonymous With USS Sum in the Study Protocol) | Baseline, Week 1, Week 4, Week 12 | Frequency-Urgency Sum 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). |
| Diary Dry Rate: Percentage of Participants With no Urgency Urinary Incontinence (UUI) in the 3-day Bladder Diary | Week 1, Week 4, Week 12 | Diary dry rate: percentage of participants 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). |
| Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Baseline, Week 1, Week, 4, Week 12 | Number of participants in 4-point category: ≥2 points improvement (major improvement; negative change from baseline); 1 point improvement (minor improvement); no change; deterioration (positive change from baseline), 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 Formerly Known as Patient Perception of Urgency Scale (PPUS) in the Protocol. | Baseline, Week 1, Week, 4, Week 12 | Number of participants in 3-point category: improvement \[≥1-point improvement\]; no change; deterioration \[≥1-point decrease\], based on UPS score (rated on 3-point scale: 1=not able to hold urine; 3=able to finish what I am doing). Score change calculated as score at observation minus score at baseline; re-scaled to 3-point categorical variables. |
| Change From Baseline in Overactive Bladder Questionnaire (OAB-q): Symptom Bother Score at Week 12 | 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 \[(Actual total raw score - lowest possible value of raw score)/range\]\*100. Higher scores values indicative of greater symptom bother. Negative change in Symptom Bother Score indicates improvement. |
| Change From Baseline in Overactive Bladder Questionnaire (OAB-q): Health Related Quality of Life (HRQL) at Week 12 | 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)=\[(Highest possible raw score- Actual total raw score)/Raw score range\] \* 100. Higher transformed scores indicative of better HRQL. Positive change in HRQL Score indicates improvement. |
| 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 ≥4 in diary ) per 24 hours calculated as the total number of micturitions with USS ≥4 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). |
Countries
Brazil, Bulgaria, Canada, Colombia, Costa Rica, Estonia, Germany, Greece, Hungary, India, Ireland, Latvia, Lithuania, Malaysia, Poland, Romania, Russia, Singapore, Slovakia, South Africa, South Korea, Spain, Sweden, 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.
Pre-assignment details
3867 participants entered the single-blind placebo run-in period; 2417 participants completed single-blind placebo run-in and progressed to randomization in 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 matching to treatment. | 478 |
| Tolterodine ER Capsules 4 mg PO QD for 12 weeks. Tolterodine Extended Release (ER). | 973 |
| Fesoterodine Tablets 4 mg PO QD for 1 week followed by a forced dose escalation to 8 mg PO QD for 11 weeks. | 960 |
| Total | 2,411 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-blind Treatment Period | Adverse Event | 9 | 28 | 46 |
| Double-blind Treatment Period | Death | 1 | 0 | 0 |
| Double-blind Treatment Period | Lack of Efficacy | 11 | 10 | 4 |
| Double-blind Treatment Period | Lost to Follow-up | 6 | 11 | 14 |
| Double-blind Treatment Period | Other | 13 | 20 | 18 |
| Double-blind Treatment Period | Withdrawal by Subject | 7 | 19 | 16 |
| Randomized to Double-blind Treatment | Not treated | 2 | 1 | 3 |
Baseline characteristics
| Characteristic | Total | Fesoterodine | Tolterodine ER | Placebo |
|---|---|---|---|---|
| Age, Customized ≥65 years | 878 participants | 330 participants | 354 participants | 194 participants |
| Age, Customized Between 18 and 44 years | 383 participants | 156 participants | 157 participants | 70 participants |
| Age, Customized Between 45 and 64 years | 1150 participants | 474 participants | 462 participants | 214 participants |
| Sex: Female, Male Female | 2044 Participants | 816 Participants | 818 Participants | 410 Participants |
| Sex: Female, Male Male | 367 Participants | 144 Participants | 155 Participants | 68 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 | 83 / 478 | 261 / 973 | 375 / 960 |
| serious Total, serious adverse events | 8 / 478 | 6 / 973 | 13 / 960 |
Outcome results
Primary
Change From Baseline in Mean Number of Urgency Urinary Incontinence (UUI) Episodes Per 24 Hours at 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).
Time frame: Baseline, Week 12
Population: Full analysis set (FAS): at least 1 dose of assigned treatment, data for at least 1 baseline or post-baseline efficacy assessment, and excluded 77 participants from 3 study sites with Good Clinical Practices (GCP) deviations (Fesoterodine N=30, Tolterodine ER N=31, Placebo N=16). Decision to exclude that data was made while the study was 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 | -1.62 episodes per 24 hours | Standard Error 0.07 |
| Tolterodine ER | Change From Baseline in Mean Number of Urgency Urinary Incontinence (UUI) Episodes Per 24 Hours at Week 12 | -1.74 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 | -1.95 episodes per 24 hours | Standard Error 0.05 |
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).~If normality assumptions were severely violated (proportion of non normal observations \> 5%) a non-parametric analysis was to be conducted using Van Elteren's test stratified by baseline quartile of the diary variable analyzed.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: 0.0228Van 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: 0.0072Van Elteren's test
Secondary
Change From Baseline in Frequency-Urgency Sum (FUS) Per 24 Hours (Synonymous With USS Sum in the Study Protocol)
Frequency-Urgency Sum 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).
Time frame: Baseline, Week 1, Week 4, Week 12
Population: FAS; (n)=number of participants 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 (FUS) Per 24 Hours (Synonymous With USS Sum in the Study Protocol) | Week 4 [LOCF] (n=453, 929, 915) | -8.1 scores on a scale | Standard Error 0.7 |
| Placebo | Change From Baseline in Frequency-Urgency Sum (FUS) Per 24 Hours (Synonymous With USS Sum in the Study Protocol) | Week 1 (n=447, 918, 906) | -4.0 scores on a scale | Standard Error 0.6 |
| Placebo | Change From Baseline in Frequency-Urgency Sum (FUS) Per 24 Hours (Synonymous With USS Sum in the Study Protocol) | Week 12 [LOCF] (n=453, 933, 915) | -12.0 scores on a scale | Standard Error 0.7 |
| Tolterodine ER | Change From Baseline in Frequency-Urgency Sum (FUS) Per 24 Hours (Synonymous With USS Sum in the Study Protocol) | Week 4 [LOCF] (n=453, 929, 915) | -10.1 scores on a scale | Standard Error 0.6 |
| Tolterodine ER | Change From Baseline in Frequency-Urgency Sum (FUS) Per 24 Hours (Synonymous With USS Sum in the Study Protocol) | Week 1 (n=447, 918, 906) | -4.8 scores on a scale | Standard Error 0.5 |
| Tolterodine ER | Change From Baseline in Frequency-Urgency Sum (FUS) Per 24 Hours (Synonymous With USS Sum in the Study Protocol) | Week 12 [LOCF] (n=453, 933, 915) | -13.2 scores on a scale | Standard Error 0.6 |
| Fesoterodine | Change From Baseline in Frequency-Urgency Sum (FUS) Per 24 Hours (Synonymous With USS Sum in the Study Protocol) | Week 1 (n=447, 918, 906) | -5.5 scores on a scale | Standard Error 0.5 |
| Fesoterodine | Change From Baseline in Frequency-Urgency Sum (FUS) Per 24 Hours (Synonymous With USS Sum in the Study Protocol) | Week 12 [LOCF] (n=453, 933, 915) | -15.6 scores on a scale | Standard Error 0.6 |
| Fesoterodine | Change From Baseline in Frequency-Urgency Sum (FUS) Per 24 Hours (Synonymous With USS Sum in the Study Protocol) | Week 4 [LOCF] (n=453, 929, 915) | -12.0 scores on a scale | Standard Error 0.6 |
Comparison: Treatment difference fesoterodine vs placebo at Week 1.p-value: 0.013695% CI: [-2.7, -0.3]ANCOVA
Comparison: Treatment difference Tolterodine ER vs placebo at Week 1.p-value: 0.191895% CI: [-2, 0.4]ANCOVA
Comparison: Treatment difference Tolterodine ER vs Fesoterodine at Week 1.p-value: 0.150595% CI: [-1.7, 0.3]ANCOVA
Comparison: Treatment difference fesoterodine vs placebo at Week 4.p-value: <0.000195% CI: [-5.2, -2.6]ANCOVA
Comparison: Treatment difference Tolterodine ER vs placebo at Week 4.p-value: 0.003495% CI: [-3.3, -0.7]ANCOVA
Comparison: Treatment difference Tolterodine ER vs Fesoterodine at Week 4.p-value: 0.000695% CI: [-3, -0.8]ANCOVA
Comparison: Treatment difference fesoterodine vs placebo at Week 12.p-value: <0.000195% CI: [-5, -2.3]ANCOVA
Comparison: Treatment difference Tolterodine ER vs placebo at Week 12.p-value: 0.085995% CI: [-2.5, 0.2]ANCOVA
Comparison: Treatment difference Tolterodine ER vs Fesoterodine at Week 12.p-value: <0.000195% CI: [-3.6, -1.4]ANCOVA
Secondary
Change From Baseline in Mean Number of Micturitions Per 24 Hours
The mean number of micturitions was calculated as the total number of micturitions divided by the total number of diary days collected at that visit.
Time frame: Baseline, Week 1, Week 4, Week 12
Population: FAS; (n)=number of participants 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=454, 931, 916) | -1.5 micturitions per 24 hours | Standard Error 0.1 |
| Placebo | Change From Baseline in Mean Number of Micturitions Per 24 Hours | Week 1 (n=448, 921, 908) | -0.8 micturitions per 24 hours | Standard Error 0.1 |
| Placebo | Change From Baseline in Mean Number of Micturitions Per 24 Hours | Week 12 [LOCF] (n=454, 935, 916) | -2.0 micturitions per 24 hours | Standard Error 0.1 |
| Tolterodine ER | Change From Baseline in Mean Number of Micturitions Per 24 Hours | Week 4 [LOCF] (n=454, 931, 916) | -1.8 micturitions per 24 hours | Standard Error 0.1 |
| Tolterodine ER | Change From Baseline in Mean Number of Micturitions Per 24 Hours | Week 1 (n=448, 921, 908) | -1.0 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=454, 935, 916) | -2.3 micturitions per 24 hours | Standard Error 0.1 |
| Fesoterodine | Change From Baseline in Mean Number of Micturitions Per 24 Hours | Week 1 (n=448, 921, 908) | -1.0 micturitions per 24 hours | Standard Error 0.1 |
| Fesoterodine | Change From Baseline in Mean Number of Micturitions Per 24 Hours | Week 12 [LOCF] (n=454, 935, 916) | -2.6 micturitions per 24 hours | Standard Error 0.1 |
| Fesoterodine | Change From Baseline in Mean Number of Micturitions Per 24 Hours | Week 4 [LOCF] (n=454, 931, 916) | -2.1 micturitions per 24 hours | Standard Error 0.1 |
Comparison: Treatment difference fesoterodine vs placebo at Week 1.p-value: 0.016195% CI: [-0.5, -0.1]ANCOVA
Comparison: Treatment difference Tolterodine ER vs placebo at Week 1.p-value: 0.094495% CI: [-0.4, 0]ANCOVA
Comparison: Treatment difference fesoterodine vs Tolterodine ER at Week 1.p-value: 0.361395% CI: [-0.3, 0.1]ANCOVA
Comparison: Treatment difference fesoterodine vs placebo at Week 4.p-value: <0.000195% CI: [-0.9, -0.4]ANCOVA
Comparison: Treatment difference Tolterodine ER vs placebo at Week 4.p-value: 0.004395% CI: [-0.6, -0.1]ANCOVA
Comparison: Treatment difference fesoterodine vs Tolterodine ER at Week 4.p-value: 0.018695% CI: [-0.5, 0]ANCOVA
Comparison: Treatment difference fesoterodine vs placebo at Week 12.p-value: <0.000195% CI: [-0.9, -0.4]ANCOVA
Comparison: Treatment difference Tolterodine ER vs placebo at Week 12.p-value: 0.040795% CI: [-0.6, 0]ANCOVA
Comparison: Treatment difference fesoterodine vs Tolterodine ER at Week 12.p-value: 0.001695% CI: [-0.6, -0.1]ANCOVA
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 total number of all micturitions divided by the total number of diary days collected at that visit. Nocturnal micturitions are those recorded in the Bedtime section of the diary. Nocturnal (Bedtime) was defined as the time the participant went to bed until he/she arose to start the next day.
Time frame: Baseline, Week 1, Week 4, Week 12
Population: FAS; (n)=number of participants with baseline nocturnal micturitions \>0 per 24 hours and 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=437, 888, 879) | -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 12 [LOCF] (n=437, 892, 879) | -0.5 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=432, 879, 871) | -0.2 nocturnal micturitions per 24 hours | Standard Error 0.1 |
| Tolterodine ER | Change From Baseline in Mean Number of Nocturnal Micturitions Per 24 Hours | Week 12 [LOCF] (n=437, 892, 879) | -0.6 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=432, 879, 871) | -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 4 [LOCF] (n=437, 888, 879) | -0.5 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=437, 892, 879) | -0.7 nocturnal micturitions per 24 hours | Standard Error 0 |
| Fesoterodine | Change From Baseline in Mean Number of Nocturnal Micturitions Per 24 Hours | Week 1 (n=432, 879, 871) | -0.3 nocturnal micturitions per 24 hours | Standard Error 0 |
| Fesoterodine | Change From Baseline in Mean Number of Nocturnal Micturitions Per 24 Hours | Week 4 [LOCF] (n=437, 888, 879) | -0.5 nocturnal micturitions per 24 hours | Standard Error 0 |
Comparison: Treatment difference fesoterodine vs placebo at Week 1.p-value: 0.382395% CI: [-0.1, 0.1]ANCOVA
Comparison: Treatment difference Tolterodine ER vs placebo at Week 1.p-value: 0.480295% CI: [-0.1, 0.1]ANCOVA
Comparison: Treatment difference fesoterodine vs Tolterodine ER at Week 1.p-value: 0.835595% CI: [-0.1, 0.1]ANCOVA
Comparison: Treatment difference fesoterodine vs placebo at Week 4.p-value: 0.028695% CI: [-0.12, 0]ANCOVA
Comparison: Treatment difference Tolterodine ER vs placebo at Week 4.p-value: 0.079495% CI: [-0.2, 0]ANCOVA
Comparison: Treatment difference fesoterodine vs Tolterodine ER at Week 4.p-value: 0.590695% CI: [-0.1, 0.1]ANCOVA
Comparison: Treatment difference fesoterodine vs placebo at Week 12.p-value: 0.013495% CI: [-0.3, 0]ANCOVA
Comparison: Treatment difference Tolterodine ER vs placebo at Week 12.p-value: 0.175995% CI: [-0.2, 0]ANCOVA
Comparison: Treatment difference fesoterodine vs Tolterodine ER at Week 12.p-value: 0.166195% CI: [-0.2, 0]ANCOVA
Secondary
Change From Baseline in Mean Number of Severe Urgency Episodes Per 24 Hours
Mean number of severe urgency episodes (USS rating ≥4 in diary ) per 24 hours calculated as the total number of micturitions with USS ≥4 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).
Time frame: Baseline, Week 1, Week 4, Week 12
Population: FAS; (n)=number of participants with baseline severe urgency episodes \>0 per 24 hours and 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 (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean Number of Severe Urgency Episodes Per 24 Hours | Week 12 [LOCF] (n=452, 930, 911) | -3.01 severe urgency episodes per 24 hours | Standard Error 0.17 |
| Placebo | Change From Baseline in Mean Number of Severe Urgency Episodes Per 24 Hours | Week 1 (n=446, 915, 902) | -1.14 severe urgency episodes per 24 hours | Standard Error 0.13 |
| Placebo | Change From Baseline in Mean Number of Severe Urgency Episodes Per 24 Hours | Week 4 [LOCF] (n=452, 926, 911) | -2.14 severe urgency episodes per 24 hours | Standard Error 0.16 |
| Tolterodine ER | Change From Baseline in Mean Number of Severe Urgency Episodes Per 24 Hours | Week 12 [LOCF] (n=452, 930, 911) | -3.39 severe urgency episodes per 24 hours | Standard Error 0.13 |
| Tolterodine ER | Change From Baseline in Mean Number of Severe Urgency Episodes Per 24 Hours | Week 1 (n=446, 915, 902) | -1.34 severe urgency episodes per 24 hours | Standard Error 0.1 |
| Tolterodine ER | Change From Baseline in Mean Number of Severe Urgency Episodes Per 24 Hours | Week 4 [LOCF] (n=452, 926, 911) | -2.71 severe urgency episodes per 24 hours | Standard Error 0.12 |
| Fesoterodine | Change From Baseline in Mean Number of Severe Urgency Episodes Per 24 Hours | Week 12 [LOCF] (n=452, 930, 911) | -4.08 severe urgency episodes per 24 hours | Standard Error 0.13 |
| Fesoterodine | Change From Baseline in Mean Number of Severe Urgency Episodes Per 24 Hours | Week 4 [LOCF] (n=452, 926, 911) | -3.21 severe urgency episodes per 24 hours | Standard Error 0.12 |
| Fesoterodine | Change From Baseline in Mean Number of Severe Urgency Episodes Per 24 Hours | Week 1 (n=446, 915, 902) | -1.58 severe urgency episodes per 24 hours | Standard Error 0.11 |
Comparison: Treatment difference fesoterodine vs placebo at Week 1. Treatment effects estimated by Winsorized means (5% of the tails were censored, ie, replaced with the value at the 5th and 95 percentile, respectively).~If normality assumptions were severely violated (proportion of non normal observations \> 5%) a non-parametric analysis was to be conducted using Van Elteren's test stratified by baseline quartile of the diary variable analyzed.p-value: 0.0576Van Elteren's Test
Comparison: Treatment difference Tolterodine ER vs placebo at Week 1. Treatment effects estimated by Winsorized means (5% of the tails were censored, ie, replaced with the value at the 5th and 95 percentile, respectively).p-value: 0.223Van Elteren's Test
Comparison: Treatment difference fesoterodine vs Tolterodine ER at Week 1. Treatment effects estimated by Winsorized means (5% of the tails were censored, ie, replaced with the value at the 5th and 95 percentile, respectively).p-value: 0.3555Van Elteren's Test
Comparison: Treatment difference fesoterodine vs placebo at Week 4. Treatment effects estimated by Winsorized means (5% of the tails were censored, ie, replaced with the value at the 5th and 95 percentile, respectively).p-value: <0.0001Van Elteren's Test
Comparison: Treatment difference Tolterodine ER vs placebo at Week 4. Treatment effects estimated by Winsorized means (5% of the tails were censored, ie, replaced with the value at the 5th and 95 percentile, respectively).p-value: 0.0009Van Elteren's Test
Comparison: Treatment difference fesoterodine vs Tolterodine ER at Week 4. Treatment effects estimated by Winsorized means (5% of the tails were censored, ie, replaced with the value at the 5th and 95 percentile, respectively).p-value: 0.0071Van Elteren's Test
Comparison: Treatment difference fesoterodine 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 95 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 95 percentile, respectively).p-value: 0.1764Van 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 95 percentile, respectively).p-value: 0.0001Van Elteren's Test
Secondary
Change From Baseline in Mean Number of Urgency Urinary Episodes Per 24 Hours (Urinary Sensation Scale ≥3 in the Diary)
Urgency Urinary episodes per 24 hours: total number of micturitions with Urinary Sensation Scale (USS) of ≥3 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).
Time frame: Baseline, Week 1, Week 4, Week 12
Population: FAS; (n)=number of participants with baseline urgency episodes \>0 per 24 hours and 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 Urgency Urinary Episodes Per 24 Hours (Urinary Sensation Scale ≥3 in the Diary) | Week 12 [LOCF] (n=453, 933, 915) | -3.2 episodes per 24 hours | Standard Error 0.2 |
| Placebo | Change From Baseline in Mean Number of Urgency Urinary Episodes Per 24 Hours (Urinary Sensation Scale ≥3 in the Diary) | Week 4 [LOCF] (n=453, 929, 915) | -1.9 episodes per 24 hours | Standard Error 0.2 |
| Placebo | Change From Baseline in Mean Number of Urgency Urinary Episodes Per 24 Hours (Urinary Sensation Scale ≥3 in the Diary) | Week 1 (n=447, 918, 906) | -0.8 episodes per 24 hours | Standard Error 0.2 |
| Tolterodine ER | Change From Baseline in Mean Number of Urgency Urinary Episodes Per 24 Hours (Urinary Sensation Scale ≥3 in the Diary) | Week 12 [LOCF] (n=453, 933, 915) | -3.5 episodes per 24 hours | Standard Error 0.2 |
| Tolterodine ER | Change From Baseline in Mean Number of Urgency Urinary Episodes Per 24 Hours (Urinary Sensation Scale ≥3 in the Diary) | Week 1 (n=447, 918, 906) | -1.0 episodes per 24 hours | Standard Error 0.1 |
| Tolterodine ER | Change From Baseline in Mean Number of Urgency Urinary Episodes Per 24 Hours (Urinary Sensation Scale ≥3 in the Diary) | Week 4 [LOCF] (n=453, 929, 915) | -2.5 episodes per 24 hours | Standard Error 0.2 |
| Fesoterodine | Change From Baseline in Mean Number of Urgency Urinary Episodes Per 24 Hours (Urinary Sensation Scale ≥3 in the Diary) | Week 4 [LOCF] (n=453, 929, 915) | -3.1 episodes per 24 hours | Standard Error 0.2 |
| Fesoterodine | Change From Baseline in Mean Number of Urgency Urinary Episodes Per 24 Hours (Urinary Sensation Scale ≥3 in the Diary) | Week 1 (n=447, 918, 906) | -1.2 episodes per 24 hours | Standard Error 0.2 |
| Fesoterodine | Change From Baseline in Mean Number of Urgency Urinary Episodes Per 24 Hours (Urinary Sensation Scale ≥3 in the Diary) | Week 12 [LOCF] (n=453, 933, 915) | -4.2 episodes per 24 hours | Standard Error 0.2 |
Comparison: Treatment difference fesoterodine vs placebo at Week 1.p-value: 0.037495% CI: [-0.7, 0]ANCOVA
Comparison: Treatment difference Tolterodine ER vs placebo at Week 1.p-value: 0.316195% CI: [-0.5, 0.2]ANCOVA
Comparison: Treatment difference Tolterodine ER vs Fesoterodine at Week 1.p-value: 0.181795% CI: [-0.5, 0.1]ANCOVA
Comparison: Treatment difference fesoterodine vs placebo at Week 4.p-value: <0.000195% CI: [-1.6, -0.8]ANCOVA
Comparison: Treatment difference Tolterodine ER vs placebo at Week 4.p-value: 0.005495% CI: [-1, -0.2]ANCOVA
Comparison: Treatment difference Tolterodine ER vs Fesoterodine at Week 4.p-value: 0.000595% CI: [-0.9, -0.3]ANCOVA
Comparison: Treatment difference fesoterodine vs placebo at Week 12.p-value: <0.000195% CI: [-1.5, -0.6]ANCOVA
Comparison: Treatment difference Tolterodine ER vs placebo at Week 12.p-value: 0.146795% CI: [-0.7, 0.1]ANCOVA
Comparison: Treatment difference Tolterodine ER vs Fesoterodine at Week 12.p-value: <0.000195% CI: [-1.1, -0.4]ANCOVA
Secondary
Change From Baseline in Mean Number of Urgency Urinary Incontinence (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).
Time frame: Baseline, Week 1, Week 4
Population: FAS; (n)=number of participants with baseline UUI \>0 per 24 hours and non-missing change from baseline to respective post-baseline value (Week 1 or Week 4 \[LOCF\] for placebo, tolterodine ER, and fesoterodine, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean Number of Urgency Urinary Incontinence (UUI) Episodes Per 24 Hours at Week 1 and Week 4 | Week 1 (n=442, 911, 899) | -0.80 episodes per 24 hours | Standard Error 0.06 |
| Placebo | Change From Baseline in Mean Number of Urgency Urinary Incontinence (UUI) Episodes Per 24 Hours at Week 1 and Week 4 | Week 4 [LOCF] (n=448, 922, 908) | -1.31 episodes per 24 hours | Standard Error 0.07 |
| Tolterodine ER | Change From Baseline in Mean Number of Urgency Urinary Incontinence (UUI) Episodes Per 24 Hours at Week 1 and Week 4 | Week 1 (n=442, 911, 899) | -0.95 episodes per 24 hours | Standard Error 0.05 |
| Tolterodine ER | Change From Baseline in Mean Number of Urgency Urinary Incontinence (UUI) Episodes Per 24 Hours at Week 1 and Week 4 | Week 4 [LOCF] (n=448, 922, 908) | -1.52 episodes per 24 hours | Standard Error 0.05 |
| Fesoterodine | Change From Baseline in Mean Number of Urgency Urinary Incontinence (UUI) Episodes Per 24 Hours at Week 1 and Week 4 | Week 1 (n=442, 911, 899) | -1.03 episodes per 24 hours | Standard Error 0.05 |
| Fesoterodine | Change From Baseline in Mean Number of Urgency Urinary Incontinence (UUI) Episodes Per 24 Hours at Week 1 and Week 4 | Week 4 [LOCF] (n=448, 922, 908) | -1.68 episodes per 24 hours | Standard Error 0.05 |
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).~If normality assumptions were severely violated (proportion of non normal observations \> 5%) a non-parametric analysis was to be conducted using Van Elteren's test stratified by baseline quartile of the diary variable analyzed.p-value: 0.0006Van 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: 0.0202Van 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: 0.2126Van 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: 0.0019Van 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: 0.0148Van Elteren's Test
Secondary
Change From Baseline in Mean Urinary Sensation Scale (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 total number of micturitions per 24 hours with non-missing rating 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).
Time frame: Baseline, Week 1, Week 4, Week 12
Population: FAS; (n)=number of participants 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 Urinary Sensation Scale (USS) Rating Per Micturition Per 24 Hours. | Week 4 [LOCF] (n=453, 929, 915) | -0.3 scores on a scale | Standard Error 0 |
| Placebo | Change From Baseline in Mean Urinary Sensation Scale (USS) Rating Per Micturition Per 24 Hours. | Week 1 (n=447, 918, 906) | -0.2 scores on a scale | Standard Error 0 |
| Placebo | Change From Baseline in Mean Urinary Sensation Scale (USS) Rating Per Micturition Per 24 Hours. | Week 12 [LOCF] (n=453, 933, 915) | -0.6 scores on a scale | Standard Error 0 |
| Tolterodine ER | Change From Baseline in Mean Urinary Sensation Scale (USS) Rating Per Micturition Per 24 Hours. | Week 4 [LOCF] (n=453, 929, 915) | -0.4 scores on a scale | Standard Error 0 |
| Tolterodine ER | Change From Baseline in Mean Urinary Sensation Scale (USS) Rating Per Micturition Per 24 Hours. | Week 1 (n=447, 918, 906) | -0.2 scores on a scale | Standard Error 0 |
| Tolterodine ER | Change From Baseline in Mean Urinary Sensation Scale (USS) Rating Per Micturition Per 24 Hours. | Week 12 [LOCF] (n=453, 933, 915) | -0.6 scores on a scale | Standard Error 0 |
| Fesoterodine | Change From Baseline in Mean Urinary Sensation Scale (USS) Rating Per Micturition Per 24 Hours. | Week 1 (n=447, 918, 906) | -0.2 scores on a scale | Standard Error 0 |
| Fesoterodine | Change From Baseline in Mean Urinary Sensation Scale (USS) Rating Per Micturition Per 24 Hours. | Week 12 [LOCF] (n=453, 933, 915) | -0.7 scores on a scale | Standard Error 0 |
| Fesoterodine | Change From Baseline in Mean Urinary Sensation Scale (USS) Rating Per Micturition Per 24 Hours. | Week 4 [LOCF] (n=453, 929, 915) | -0.5 scores on a scale | Standard Error 0 |
Comparison: Treatment difference fesoterodine vs placebo at Week 1.p-value: 0.070195% CI: [-0.1, 0]ANCOVA
Comparison: Treatment difference Tolterodine ER vs placebo at Week 1.p-value: 0.482395% CI: [-0.1, 0]ANCOVA
Comparison: Treatment difference Tolterodine ER vs Fesoterodine at Week 1.p-value: 0.170295% CI: [-0.1, 0]ANCOVA
Comparison: Treatment difference fesoterodine vs placebo at Week 4.p-value: <0.000195% CI: [-0.3, -0.1]ANCOVA
Comparison: Treatment difference Tolterodine ER vs placebo at Week 4.p-value: 0.005995% CI: [-0.2, 0]ANCOVA
Comparison: Treatment difference Tolterodine ER vs Fesoterodine at Week 4.p-value: 0.001495% CI: [-0.2, 0]ANCOVA
Comparison: Treatment difference fesoterodine vs placebo at Week 12.p-value: <0.000195% CI: [-0.3, -0.1]ANCOVA
Comparison: Treatment difference Tolterodine ER vs placebo at Week 12.p-value: 0.31195% CI: [-0.1, 0]ANCOVA
Comparison: Treatment difference Tolterodine ER vs Fesoterodine at Week 12.p-value: 0.000495% CI: [-0.2, -0.1]ANCOVA
Secondary
Change From Baseline in Mean Voided Volume Per Micturition
Mean voided volume in milliliters (mL) 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 participants with non-missing numerical change from baseline to the respective post-baseline value (Week 1, Week 4 \[Last Observation Carried Forward (LOCF)\], or Week 12 \[LOCF\]) for placebo, tolterodine ER, and fesoterodine, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean Voided Volume Per Micturition | Week 12 [LOCF] (n=452, 930, 912) | 17.34 mL | Standard Error 2.4 |
| Placebo | Change From Baseline in Mean Voided Volume Per Micturition | Week 4 [LOCF] (n=452, 927, 909) | 14.27 mL | Standard Error 2.28 |
| Placebo | Change From Baseline in Mean Voided Volume Per Micturition | Week 1 (n=447, 917, 895) | 9.80 mL | Standard Error 1.92 |
| Tolterodine ER | Change From Baseline in Mean Voided Volume Per Micturition | Week 12 [LOCF] (n=452, 930, 912) | 28.43 mL | Standard Error 1.82 |
| Tolterodine ER | Change From Baseline in Mean Voided Volume Per Micturition | Week 1 (n=447, 917, 895) | 15.65 mL | Standard Error 1.43 |
| Tolterodine ER | Change From Baseline in Mean Voided Volume Per Micturition | Week 4 [LOCF] (n=452, 927, 909) | 26.43 mL | Standard Error 1.76 |
| Fesoterodine | Change From Baseline in Mean Voided Volume Per Micturition | Week 4 [LOCF] (n=452, 927, 909) | 32.26 mL | Standard Error 1.94 |
| Fesoterodine | Change From Baseline in Mean Voided Volume Per Micturition | Week 1 (n=447, 917, 895) | 18.63 mL | Standard Error 1.55 |
| Fesoterodine | Change From Baseline in Mean Voided Volume Per Micturition | Week 12 [LOCF] (n=452, 930, 912) | 34.47 mL | Standard Error 2.06 |
Comparison: Treatment difference fesoterodine vs placebo at Week 1. Treatment effects estimated by Winsorized means (5% of the tails were censored, ie, replaced with the value at the 5th and 95th percentile, respectively).~If normality assumptions were severely violated (proportion of non normal observations \> 5%) a non-parametric analysis was to be conducted using Van Elteren's test stratified by baseline quartile of the diary variable analyzed.p-value: 0.002Van Elteren's Test
Comparison: Treatment difference tolterodine ER vs placebo at Week 1. 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: 0.0519Van Elteren's Test
Comparison: Treatment difference fesoterodine vs tolterodine ER at Week 1. 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: 0.1503Van Elteren's Test
Comparison: Treatment difference fesoterodine vs placebo at Week 4. 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: <0.0001Van Elteren's Test
Comparison: Treatment difference tolterodine ER vs placebo at Week 4. 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: 0.0002Van Elteren's Test
Comparison: Treatment difference fesoterodine vs tolterodine ER at Week 4. 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: 0.013Van Elteren's
Comparison: Treatment difference fesoterodine 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: <0.0001Van 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: 0.0021Van 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: 0.0525Van Elteren's Test
Secondary
Change From Baseline in Overactive Bladder Questionnaire (OAB-q): Health Related Quality of Life (HRQL) at 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)=\[(Highest possible raw score- Actual total raw score)/Raw score range\] \* 100. Higher transformed scores indicative of better HRQL. Positive change in HRQL Score indicates improvement.
Time frame: Baseline, Week 12
Population: FAS; (n)=number of participants with non-missing numerical change from baseline to the respective post-baseline value (Week 12 \[LOCF\]) for placebo, tolterodine ER, and fesoterodine, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Overactive Bladder Questionnaire (OAB-q): Health Related Quality of Life (HRQL) at Week 12 | HRQL scale score total (n=431, 892, 873) | 17.2 scores on a scale | Standard Error 1.2 |
| Placebo | Change From Baseline in Overactive Bladder Questionnaire (OAB-q): Health Related Quality of Life (HRQL) at Week 12 | HRQL concern domain (n=434, 894, 875) | 20.2 scores on a scale | Standard Error 1.4 |
| Placebo | Change From Baseline in Overactive Bladder Questionnaire (OAB-q): Health Related Quality of Life (HRQL) at Week 12 | HRQL coping domain (n=433, 892, 875) | 19.0 scores on a scale | Standard Error 1.4 |
| Placebo | Change From Baseline in Overactive Bladder Questionnaire (OAB-q): Health Related Quality of Life (HRQL) at Week 12 | HRQL sleep domain (n=433, 894, 875) | 16.6 scores on a scale | Standard Error 1.3 |
| Placebo | Change From Baseline in Overactive Bladder Questionnaire (OAB-q): Health Related Quality of Life (HRQL) at Week 12 | HRQL social interaction domain (n=435, 894, 873) | 10.8 scores on a scale | Standard Error 1 |
| Tolterodine ER | Change From Baseline in Overactive Bladder Questionnaire (OAB-q): Health Related Quality of Life (HRQL) at Week 12 | HRQL scale score total (n=431, 892, 873) | 19.5 scores on a scale | Standard Error 1 |
| Tolterodine ER | Change From Baseline in Overactive Bladder Questionnaire (OAB-q): Health Related Quality of Life (HRQL) at Week 12 | HRQL sleep domain (n=433, 894, 875) | 18.7 scores on a scale | Standard Error 1.1 |
| Tolterodine ER | Change From Baseline in Overactive Bladder Questionnaire (OAB-q): Health Related Quality of Life (HRQL) at Week 12 | HRQL social interaction domain (n=435, 894, 873) | 12.0 scores on a scale | Standard Error 0.8 |
| Tolterodine ER | Change From Baseline in Overactive Bladder Questionnaire (OAB-q): Health Related Quality of Life (HRQL) at Week 12 | HRQL concern domain (n=434, 894, 875) | 22.5 scores on a scale | Standard Error 1.1 |
| Tolterodine ER | Change From Baseline in Overactive Bladder Questionnaire (OAB-q): Health Related Quality of Life (HRQL) at Week 12 | HRQL coping domain (n=433, 892, 875) | 22.0 scores on a scale | Standard Error 1.1 |
| Fesoterodine | Change From Baseline in Overactive Bladder Questionnaire (OAB-q): Health Related Quality of Life (HRQL) at Week 12 | HRQL concern domain (n=434, 894, 875) | 26.8 scores on a scale | Standard Error 1.1 |
| Fesoterodine | Change From Baseline in Overactive Bladder Questionnaire (OAB-q): Health Related Quality of Life (HRQL) at Week 12 | HRQL coping domain (n=433, 892, 875) | 25.9 scores on a scale | Standard Error 1.2 |
| Fesoterodine | Change From Baseline in Overactive Bladder Questionnaire (OAB-q): Health Related Quality of Life (HRQL) at Week 12 | HRQL scale score total (n=431, 892, 873) | 22.9 scores on a scale | Standard Error 1 |
| Fesoterodine | Change From Baseline in Overactive Bladder Questionnaire (OAB-q): Health Related Quality of Life (HRQL) at Week 12 | HRQL social interaction domain (n=435, 894, 873) | 13.9 scores on a scale | Standard Error 0.8 |
| Fesoterodine | Change From Baseline in Overactive Bladder Questionnaire (OAB-q): Health Related Quality of Life (HRQL) at Week 12 | HRQL sleep domain (n=433, 894, 875) | 21.0 scores on a scale | Standard Error 1.1 |
Comparison: Treatment Difference Fesoterodine vs placebo: HRQL scale score total.p-value: <0.000195% CI: [3.4, 7.9]ANCOVA
Comparison: Treatment Difference Tolterodine ER vs Placebo: HRQL scale score total.p-value: 0.042995% CI: [0.1, 4.6]ANCOVA
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER: HRQL scale score total.p-value: 0.000395% CI: [1.5, 5.2]ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo: HRQL concern domain.p-value: <0.000195% CI: [4, 9.2]ANCOVA
Comparison: Treatment Difference Placebo vs Tolterodine ER: HRQL concern domain.p-value: 0.079595% CI: [-0.3, 4.9]ANCOVA
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER: HRQL concern domain.p-value: <0.000195% CI: [2.1, 6.3]ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo: HRQL coping domain.p-value: <0.000195% CI: [4.3, 9.6]ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo: HRQL coping domain.p-value: 0.022995% CI: [0.4, 5.7]ANCOVA
Comparison: Treatment Difference Fesoterodine vs Tolterodine ER: HRQL coping domain.p-value: 0.000495% CI: [1.7, 6]ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo: HRQL sleep domain.p-value: 0.000395% CI: [2, 6.9]ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo: HRQL sleep domain.p-value: 0.092395% CI: [-0.3, 4.5]ANCOVA
Comparison: Treatment Difference Tolterodine ER vs Fesoterodine: HRQL sleep domain.p-value: 0.01895% CI: [0.4, 4.4]ANCOVA
Comparison: Treatment Difference Fesoterodine vs placebo: HRQL social interaction domain.p-value: 0.001195% CI: [1.3, 5.1]ANCOVA
Comparison: Treatment Difference Tolterodine ER vs placebo: HRQL social interaction domain.p-value: 0.220895% CI: [-0.7, 3.1]ANCOVA
Comparison: Treatment Difference Tolterodine ER vs Fesoterodine: HRQL social interaction domain.p-value: 0.011795% CI: [0.4, 3.5]ANCOVA
Secondary
Change From Baseline in Overactive Bladder Questionnaire (OAB-q): Symptom Bother Score at 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 \[(Actual total raw score - lowest possible value of raw score)/range\]\*100. Higher scores values indicative of greater symptom bother. Negative change in Symptom Bother Score indicates improvement.
Time frame: Baseline, Week 12
Population: FAS; (n)=number of participants with non-missing numerical change from baseline to the respective post-baseline value (Week 12 \[LOCF\]) for placebo, tolterodine ER, and fesoterodine, respectively.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Overactive Bladder Questionnaire (OAB-q): Symptom Bother Score at Week 12 | -21.8 scores on a scale | Standard Error 1.3 |
| Tolterodine ER | Change From Baseline in Overactive Bladder Questionnaire (OAB-q): Symptom Bother Score at Week 12 | -24.3 scores on a scale | Standard Error 1 |
| Fesoterodine | Change From Baseline in Overactive Bladder Questionnaire (OAB-q): Symptom Bother Score at Week 12 | -28.9 scores on a scale | Standard Error 1.1 |
Comparison: Treatment difference fesoterodine vs placebo at Week 12.p-value: <0.000195% CI: [-9.5, -4.7]ANCOVA
Comparison: Treatment difference Tolterodine ER vs placebo at Week 12.p-value: 0.045895% CI: [-4.8, 0]ANCOVA
Comparison: Treatment difference Tolterodine ER vs Fesoterodine at Week 12.p-value: <0.000195% CI: [-6.6, -2.7]ANCOVA
Secondary
Change From Baseline in Patient Perception of Bladder Condition (PPBC)
Number of participants in 4-point category: ≥2 points improvement (major improvement; negative change from baseline); 1 point improvement (minor improvement); no change; deterioration (positive change from baseline), 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 participants 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 1 (n=452, 931, 913) ≥2 points improvement | 43 participants |
| Placebo | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 1: 1-point improvement | 144 participants |
| Placebo | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 1: no change | 210 participants |
| Placebo | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 4: 1-point improvement | 124 participants |
| Placebo | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 4: no change | 172 participants |
| Placebo | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 12: 1-point improvement | 106 participants |
| Placebo | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 12: no change | 133 participants |
| Placebo | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 12: deterioration | 50 participants |
| Placebo | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 1: deterioration | 55 participants |
| Placebo | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 4 (n=455, 937, 918) ≥2 points improvement | 111 participants |
| Placebo | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 4: deterioration | 48 participants |
| Placebo | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 12 (n=455, 937, 918) ≥2 points improvement | 166 participants |
| Tolterodine ER | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 12 (n=455, 937, 918) ≥2 points improvement | 379 participants |
| Tolterodine ER | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 1 (n=452, 931, 913) ≥2 points improvement | 138 participants |
| Tolterodine ER | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 12: no change | 249 participants |
| Tolterodine ER | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 12: 1-point improvement | 250 participants |
| Tolterodine ER | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 4: deterioration | 64 participants |
| Tolterodine ER | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 1: no change | 434 participants |
| Tolterodine ER | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 4 (n=455, 937, 918) ≥2 points improvement | 290 participants |
| Tolterodine ER | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 12: deterioration | 59 participants |
| Tolterodine ER | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 1: deterioration | 81 participants |
| Tolterodine ER | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 4: 1-point improvement | 298 participants |
| Tolterodine ER | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 1: 1-point improvement | 278 participants |
| Tolterodine ER | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 4: no change | 285 participants |
| Fesoterodine | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 1: deterioration | 61 participants |
| Fesoterodine | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 4: no change | 250 participants |
| Fesoterodine | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 12 (n=455, 937, 918) ≥2 points improvement | 440 participants |
| Fesoterodine | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 12: deterioration | 53 participants |
| Fesoterodine | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 12: 1-point improvement | 236 participants |
| Fesoterodine | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 12: no change | 189 participants |
| Fesoterodine | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 1: 1-point improvement | 280 participants |
| Fesoterodine | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 1 (n=452, 931, 913) ≥2 points improvement | 144 participants |
| Fesoterodine | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 1: no change | 428 participants |
| Fesoterodine | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 4: deterioration | 54 participants |
| Fesoterodine | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 4 (n=455, 937, 918) ≥2 points improvement | 334 participants |
| Fesoterodine | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Week 4: 1-point improvement | 280 participants |
Comparison: Treatment difference fesoterodine vs placebo at Week 1.p-value: 0.0009Cochran-Mantel-Haenszel
Comparison: Treatment difference Tolterodine ER vs placebo at Week 1.p-value: 0.0279Cochran-Mantel-Haenszel
Comparison: Treatment difference Tolterodine ER vs Fesoterodine at Week 1.p-value: 0.2817Cochran-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 Tolterodine ER vs Fesoterodine at Week 4.p-value: 0.0177Cochran-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: 0.0107Cochran-Mantel-Haenszel
Comparison: Treatment difference Tolterodine ER vs Fesoterodine at Week 12.p-value: 0.0005Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Urgency Perception Scale (UPS). UPS Formerly Known as Patient Perception of Urgency Scale (PPUS) in the Protocol.
Number of participants in 3-point category: improvement \[≥1-point improvement\]; no change; deterioration \[≥1-point decrease\], based on UPS score (rated on 3-point scale: 1=not able to hold urine; 3=able to finish what I am doing). Score change calculated as score at observation minus score at baseline; re-scaled to 3-point categorical variables.
Time frame: Baseline, Week 1, Week, 4, Week 12
Population: FAS; (n)=number of participants 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 Formerly Known as Patient Perception of Urgency Scale (PPUS) in the Protocol. | Week 1: deterioration | 29 participants |
| Placebo | Change From Baseline in Urgency Perception Scale (UPS). UPS Formerly Known as Patient Perception of Urgency Scale (PPUS) in the Protocol. | Week 4 (n=455, 938, 918) improvement | 161 participants |
| Placebo | Change From Baseline in Urgency Perception Scale (UPS). UPS Formerly Known as Patient Perception of Urgency Scale (PPUS) in the Protocol. | Week 4: no change | 271 participants |
| Placebo | Change From Baseline in Urgency Perception Scale (UPS). UPS Formerly Known as Patient Perception of Urgency Scale (PPUS) in the Protocol. | Week 4: deterioration | 23 participants |
| Placebo | Change From Baseline in Urgency Perception Scale (UPS). UPS Formerly Known as Patient Perception of Urgency Scale (PPUS) in the Protocol. | Week 12 (n=455, 938, 918) improvement | 183 participants |
| Placebo | Change From Baseline in Urgency Perception Scale (UPS). UPS Formerly Known as Patient Perception of Urgency Scale (PPUS) in the Protocol. | Week 12: deterioration | 33 participants |
| Placebo | Change From Baseline in Urgency Perception Scale (UPS). UPS Formerly Known as Patient Perception of Urgency Scale (PPUS) in the Protocol. | Week 1 (n=452, 932, 913) improvement | 97 participants |
| Placebo | Change From Baseline in Urgency Perception Scale (UPS). UPS Formerly Known as Patient Perception of Urgency Scale (PPUS) in the Protocol. | Week 1: no change | 326 participants |
| Placebo | Change From Baseline in Urgency Perception Scale (UPS). UPS Formerly Known as Patient Perception of Urgency Scale (PPUS) in the Protocol. | Week 12: no change | 239 participants |
| Tolterodine ER | Change From Baseline in Urgency Perception Scale (UPS). UPS Formerly Known as Patient Perception of Urgency Scale (PPUS) in the Protocol. | Week 4: deterioration | 51 participants |
| Tolterodine ER | Change From Baseline in Urgency Perception Scale (UPS). UPS Formerly Known as Patient Perception of Urgency Scale (PPUS) in the Protocol. | Week 12 (n=455, 938, 918) improvement | 440 participants |
| Tolterodine ER | Change From Baseline in Urgency Perception Scale (UPS). UPS Formerly Known as Patient Perception of Urgency Scale (PPUS) in the Protocol. | Week 12: deterioration | 43 participants |
| Tolterodine ER | Change From Baseline in Urgency Perception Scale (UPS). UPS Formerly Known as Patient Perception of Urgency Scale (PPUS) in the Protocol. | Week 1 (n=452, 932, 913) improvement | 264 participants |
| Tolterodine ER | Change From Baseline in Urgency Perception Scale (UPS). UPS Formerly Known as Patient Perception of Urgency Scale (PPUS) in the Protocol. | Week 12: no change | 455 participants |
| Tolterodine ER | Change From Baseline in Urgency Perception Scale (UPS). UPS Formerly Known as Patient Perception of Urgency Scale (PPUS) in the Protocol. | Week 1: deterioration | 49 participants |
| Tolterodine ER | Change From Baseline in Urgency Perception Scale (UPS). UPS Formerly Known as Patient Perception of Urgency Scale (PPUS) in the Protocol. | Week 1: no change | 619 participants |
| Tolterodine ER | Change From Baseline in Urgency Perception Scale (UPS). UPS Formerly Known as Patient Perception of Urgency Scale (PPUS) in the Protocol. | Week 4 (n=455, 938, 918) improvement | 376 participants |
| Tolterodine ER | Change From Baseline in Urgency Perception Scale (UPS). UPS Formerly Known as Patient Perception of Urgency Scale (PPUS) in the Protocol. | Week 4: no change | 511 participants |
| Fesoterodine | Change From Baseline in Urgency Perception Scale (UPS). UPS Formerly Known as Patient Perception of Urgency Scale (PPUS) in the Protocol. | Week 4 (n=455, 938, 918) improvement | 421 participants |
| Fesoterodine | Change From Baseline in Urgency Perception Scale (UPS). UPS Formerly Known as Patient Perception of Urgency Scale (PPUS) in the Protocol. | Week 1: no change | 609 participants |
| Fesoterodine | Change From Baseline in Urgency Perception Scale (UPS). UPS Formerly Known as Patient Perception of Urgency Scale (PPUS) in the Protocol. | Week 12 (n=455, 938, 918) improvement | 495 participants |
| Fesoterodine | Change From Baseline in Urgency Perception Scale (UPS). UPS Formerly Known as Patient Perception of Urgency Scale (PPUS) in the Protocol. | Week 12: no change | 393 participants |
| Fesoterodine | Change From Baseline in Urgency Perception Scale (UPS). UPS Formerly Known as Patient Perception of Urgency Scale (PPUS) in the Protocol. | Week 4: deterioration | 30 participants |
| Fesoterodine | Change From Baseline in Urgency Perception Scale (UPS). UPS Formerly Known as Patient Perception of Urgency Scale (PPUS) in the Protocol. | Week 12: deterioration | 30 participants |
| Fesoterodine | Change From Baseline in Urgency Perception Scale (UPS). UPS Formerly Known as Patient Perception of Urgency Scale (PPUS) in the Protocol. | Week 1: deterioration | 37 participants |
| Fesoterodine | Change From Baseline in Urgency Perception Scale (UPS). UPS Formerly Known as Patient Perception of Urgency Scale (PPUS) in the Protocol. | Week 4: no change | 467 participants |
| Fesoterodine | Change From Baseline in Urgency Perception Scale (UPS). UPS Formerly Known as Patient Perception of Urgency Scale (PPUS) in the Protocol. | Week 1 (n=452, 932, 913) improvement | 267 participants |
Comparison: Treatment difference fesoterodine vs placebo at Week 1.p-value: 0.0011Cochran-Mantel-Haenszel
Comparison: Treatment difference Tolterodine ER vs placebo at Week 1.p-value: 0.0072Cochran-Mantel-Haenszel
Comparison: Treatment difference fesoterodine vs Tolterodine ER at Week 1.p-value: 0.3713Cochran-Mantel-Haenszel
Comparison: Treatment difference fesoterodine vs placebo at Week 4.p-value: 0.0002Cochran-Mantel-Haenszel
Comparison: Treatment difference Tolterodine ER vs placebo at Week 4.p-value: 0.1485Cochran-Mantel-Haenszel
Comparison: Treatment difference fesoterodine vs Tolterodine ER at Week 4.p-value: 0.004Cochran-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: 0.006Cochran-Mantel-Haenszel
Comparison: Treatment difference fesoterodine vs Tolterodine ER at Week 12.p-value: 0.0016Cochran-Mantel-Haenszel
Secondary
Diary Dry Rate: Percentage of Participants With no Urgency Urinary Incontinence (UUI) in the 3-day Bladder Diary
Diary dry rate: percentage of participants 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; (n)=number of participants with non-missing baseline and 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 | Diary Dry Rate: Percentage of Participants With no Urgency Urinary Incontinence (UUI) in the 3-day Bladder Diary | Week 1 (n=422, 911, 899) | 17.6 percentage of participants |
| Placebo | Diary Dry Rate: Percentage of Participants With no Urgency Urinary Incontinence (UUI) in the 3-day Bladder Diary | Week 12 [LOCF] (n=448, 926, 908) | 53.8 percentage of participants |
| Placebo | Diary Dry Rate: Percentage of Participants With no Urgency Urinary Incontinence (UUI) in the 3-day Bladder Diary | Week 4 [LOCF] (n=448, 922, 908) | 39.5 percentage of participants |
| Tolterodine ER | Diary Dry Rate: Percentage of Participants With no Urgency Urinary Incontinence (UUI) in the 3-day Bladder Diary | Week 1 (n=422, 911, 899) | 24.5 percentage of participants |
| Tolterodine ER | Diary Dry Rate: Percentage of Participants With no Urgency Urinary Incontinence (UUI) in the 3-day Bladder Diary | Week 4 [LOCF] (n=448, 922, 908) | 46.7 percentage of participants |
| Tolterodine ER | Diary Dry Rate: Percentage of Participants With no Urgency Urinary Incontinence (UUI) in the 3-day Bladder Diary | Week 12 [LOCF] (n=448, 926, 908) | 58.1 percentage of participants |
| Fesoterodine | Diary Dry Rate: Percentage of Participants With no Urgency Urinary Incontinence (UUI) in the 3-day Bladder Diary | Week 1 (n=422, 911, 899) | 25.1 percentage of participants |
| Fesoterodine | Diary Dry Rate: Percentage of Participants With no Urgency Urinary Incontinence (UUI) in the 3-day Bladder Diary | Week 12 [LOCF] (n=448, 926, 908) | 63.2 percentage of participants |
| Fesoterodine | Diary Dry Rate: Percentage of Participants With no Urgency Urinary Incontinence (UUI) in the 3-day Bladder Diary | Week 4 [LOCF] (n=448, 922, 908) | 51.1 percentage of participants |
Comparison: Treatment difference in continent rate for fesoterodine vs placebo at Week 1.p-value: 0.0008Cochran-Mantel-Haenszel
Comparison: Treatment difference in continent rate for Tolterodine ER vs placebo at Week 1.p-value: 0.0024Cochran-Mantel-Haenszel
Comparison: Treatment difference in continent rate for fesoterodine vs Tolterodine ER at Week 1.p-value: 0.6514Cochran-Mantel-Haenszel
Comparison: Treatment difference in continent rate for fesoterodine vs placebo at Week 4.p-value: <0.0001Cochran-Mantel-Haenszel
Comparison: Treatment difference in continent rate for Tolterodine ER vs placebo at Week 4.p-value: 0.0063Cochran-Mantel-Haenszel
Comparison: Treatment difference in continent rate for fesoterodine vs Tolterodine ER at Week 4.p-value: 0.0494Cochran-Mantel-Haenszel
Comparison: Treatment difference in continent rate for fesoterodine vs placebo at Week 12.p-value: 0.0003Cochran-Mantel-Haenszel
Comparison: Treatment difference in continent rate for Tolterodine ER vs placebo at Week 12.p-value: 0.0991Cochran-Mantel-Haenszel
Comparison: Treatment difference in continent rate for fesoterodine vs Tolterodine ER at Week 12.p-value: 0.0169Cochran-Mantel-Haenszel
Secondary
Percent Change From Baseline in Mean Number of Urgency Urinary Episodes Per 24 Hours (Urinary Sensation Scale ≥3 in the Diary)
Percent change from baseline in mean number of Urgency Urinary episodes per 24 hours (Urinary Sensation Scale ≥3 in the diary). 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; (n)=number of participants with baseline urgency episodes \>0 per 24 hours and 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 (MEDIAN) |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Mean Number of Urgency Urinary Episodes Per 24 Hours (Urinary Sensation Scale ≥3 in the Diary) | Week 1 (n=447, 918, 906) | -9.4 percent change |
| Placebo | Percent Change From Baseline in Mean Number of Urgency Urinary Episodes Per 24 Hours (Urinary Sensation Scale ≥3 in the Diary) | Week 12 [LOCF] (n=453, 933, 915) | -31.0 percent change |
| Placebo | Percent Change From Baseline in Mean Number of Urgency Urinary Episodes Per 24 Hours (Urinary Sensation Scale ≥3 in the Diary) | Week 4 [LOCF] (n=453, 929, 915) | -17.2 percent change |
| Tolterodine ER | Percent Change From Baseline in Mean Number of Urgency Urinary Episodes Per 24 Hours (Urinary Sensation Scale ≥3 in the Diary) | Week 4 [LOCF] (n=453, 929, 915) | -26.3 percent change |
| Tolterodine ER | Percent Change From Baseline in Mean Number of Urgency Urinary Episodes Per 24 Hours (Urinary Sensation Scale ≥3 in the Diary) | Week 12 [LOCF] (n=453, 933, 915) | -37.5 percent change |
| Tolterodine ER | Percent Change From Baseline in Mean Number of Urgency Urinary Episodes Per 24 Hours (Urinary Sensation Scale ≥3 in the Diary) | Week 1 (n=447, 918, 906) | -12.0 percent change |
| Fesoterodine | Percent Change From Baseline in Mean Number of Urgency Urinary Episodes Per 24 Hours (Urinary Sensation Scale ≥3 in the Diary) | Week 12 [LOCF] (n=453, 933, 915) | -45.5 percent change |
| Fesoterodine | Percent Change From Baseline in Mean Number of Urgency Urinary Episodes Per 24 Hours (Urinary Sensation Scale ≥3 in the Diary) | Week 1 (n=447, 918, 906) | -11.8 percent change |
| Fesoterodine | Percent Change From Baseline in Mean Number of Urgency Urinary Episodes Per 24 Hours (Urinary Sensation Scale ≥3 in the Diary) | Week 4 [LOCF] (n=453, 929, 915) | -32.1 percent change |
Comparison: Treatment difference fesoterodine vs placebo at Week 1.p-value: 0.0828ANCOVA
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: 0.0008ANCOVA
Comparison: Treatment difference Tolterodine ER vs Fesoterodine at Week 4.p-value: 0.0022ANCOVA
Comparison: Treatment difference fesoterodine vs placebo at Week 12.p-value: <0.0001ANCOVA
Comparison: Treatment difference Tolterodine ER vs Fesoterodine at Week 12.p-value: 0.0008ANCOVA
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 1 or 4 or 12 - baseline)/baseline).
Time frame: Baseline, Week 1, Week 4, Week 12
Population: FAS; (n)=number of participants 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=454, 931, 916) | -13.4 percent change |
| Placebo | Percent Change From Baseline of Micturitions Per 24 Hours | Week 1 (n=448, 921, 908) | -7.1 percent change |
| Placebo | Percent Change From Baseline of Micturitions Per 24 Hours | Week 12 [LOCF] (n=454, 935, 916) | -18.2 percent change |
| Tolterodine ER | Percent Change From Baseline of Micturitions Per 24 Hours | Week 4 [LOCF] (n=454, 931, 916) | -16.7 percent change |
| Tolterodine ER | Percent Change From Baseline of Micturitions Per 24 Hours | Week 1 (n=448, 921, 908) | -9.4 percent change |
| Tolterodine ER | Percent Change From Baseline of Micturitions Per 24 Hours | Week 12 [LOCF] (n=454, 935, 916) | -20.8 percent change |
| Fesoterodine | Percent Change From Baseline of Micturitions Per 24 Hours | Week 1 (n=448, 921, 908) | -9.0 percent change |
| Fesoterodine | Percent Change From Baseline of Micturitions Per 24 Hours | Week 12 [LOCF] (n=454, 935, 916) | -23.5 percent change |
| Fesoterodine | Percent Change From Baseline of Micturitions Per 24 Hours | Week 4 [LOCF] (n=454, 931, 916) | -18.9 percent change |
Comparison: Treatment difference fesoterodine vs placebo at Week 1.p-value: 0.0217ANCOVA
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: 0.002ANCOVA
Comparison: Treatment difference fesoterodine vs Tolterodine ER at Week 4.p-value: 0.0217ANCOVA
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: 0.0421ANCOVA
Comparison: Treatment difference fesoterodine vs Tolterodine ER at Week 12.p-value: 0.0023ANCOVA
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 1 or 4 or 12 - baseline)/baseline). Nocturnal micturitions are those recorded in the Bedtime section of the diary. Nocturnal (Bedtime) was defined as the time the participant went to bed until he/she arose to start the next day.
Time frame: Baseline, Week 1, Week 4, Week 12
Population: FAS; (n)=number of participants with baseline nocturnal micturitions \>0 per 24 hours and 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 12 [LOCF] (n=437, 892, 879) | -27.3 percent change |
| Placebo | Percent Change From Baseline of Nocturnal Micturitions Per 24 Hours | Week 1 (n=432, 879, 871) | -7.7 percent change |
| Placebo | Percent Change From Baseline of Nocturnal Micturitions Per 24 Hours | Week 4 [LOCF] (n=437, 888, 879) | -20.0 percent change |
| Tolterodine ER | Percent Change From Baseline of Nocturnal Micturitions Per 24 Hours | Week 12 [LOCF] (n=437, 892, 879) | -33.3 percent change |
| Tolterodine ER | Percent Change From Baseline of Nocturnal Micturitions Per 24 Hours | Week 1 (n=432, 879, 871) | -14.3 percent change |
| Tolterodine ER | Percent Change From Baseline of Nocturnal Micturitions Per 24 Hours | Week 4 [LOCF] (n=437, 888, 879) | -25.0 percent change |
| Fesoterodine | Percent Change From Baseline of Nocturnal Micturitions Per 24 Hours | Week 12 [LOCF] (n=437, 892, 879) | -33.3 percent change |
| Fesoterodine | Percent Change From Baseline of Nocturnal Micturitions Per 24 Hours | Week 4 [LOCF] (n=437, 888, 879) | -25.0 percent change |
| Fesoterodine | Percent Change From Baseline of Nocturnal Micturitions Per 24 Hours | Week 1 (n=432, 879, 871) | -12.5 percent change |
Comparison: Treatment difference fesoterodine vs placebo at Week 4.p-value: 0.0021ANCOVA
Comparison: Treatment difference fesoterodine vs placebo at Week 12.p-value: 0.02ANCOVA
Secondary
Percent Change From Baseline of Severe Urgency Episodes Per 24 Hours
Percent change calculated as change in severe urgency episodes (USS rating ≥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; (n)=number of participants with baseline severe urgency episodes \>0 per 24 hours and 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 12 [LOCF] (n=452, 930, 911) | -61.0 percent change |
| Placebo | Percent Change From Baseline of Severe Urgency Episodes Per 24 Hours | Week 1 (n=446, 915, 902) | -19.7 percent change |
| Placebo | Percent Change From Baseline of Severe Urgency Episodes Per 24 Hours | Week 4 [LOCF] (n=452, 926, 911) | -41.7 percent change |
| Tolterodine ER | Percent Change From Baseline of Severe Urgency Episodes Per 24 Hours | Week 12 [LOCF] (n=452, 930, 911) | -69.2 percent change |
| Tolterodine ER | Percent Change From Baseline of Severe Urgency Episodes Per 24 Hours | Week 1 (n=446, 915, 902) | -24.1 percent change |
| Tolterodine ER | Percent Change From Baseline of Severe Urgency Episodes Per 24 Hours | Week 4 [LOCF] (n=452, 926, 911) | -55.6 percent change |
| Fesoterodine | Percent Change From Baseline of Severe Urgency Episodes Per 24 Hours | Week 12 [LOCF] (n=452, 930, 911) | -79.3 percent change |
| Fesoterodine | Percent Change From Baseline of Severe Urgency Episodes Per 24 Hours | Week 4 [LOCF] (n=452, 926, 911) | -61.1 percent change |
| Fesoterodine | Percent Change From Baseline of Severe Urgency Episodes Per 24 Hours | Week 1 (n=446, 915, 902) | -25.0 percent change |
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: 0.0003ANCOVA
Comparison: Treatment difference Tolterodine ER vs Fesoterodine at Week 4.p-value: 0.0302ANCOVA
Comparison: Treatment difference fesoterodine vs placebo at Week 12.p-value: <0.0001ANCOVA
Comparison: Treatment difference Tolterodine ER vs Fesoterodine at Week 12.p-value: 0.0007ANCOVA
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; (n)=number of participants with baseline UUI \>0 per 24 hours and 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=448, 922, 908) | -75.0 percent change |
| Placebo | Percent Change From Baseline of UUI Episodes Per 24 Hours | Week 1 (n=442, 911, 899) | -40.8 percent change |
| Placebo | Percent Change From Baseline of UUI Episodes Per 24 Hours | Week 12 [LOCF] (n=448, 926, 908) | -100.0 percent change |
| Tolterodine ER | Percent Change From Baseline of UUI Episodes Per 24 Hours | Week 4 [LOCF] (n=448, 922, 908) | -88.9 percent change |
| Tolterodine ER | Percent Change From Baseline of UUI Episodes Per 24 Hours | Week 1 (n=442, 911, 899) | -50.0 percent change |
| Tolterodine ER | Percent Change From Baseline of UUI Episodes Per 24 Hours | Week 12 [LOCF] (n=448, 926, 908) | -100.0 percent change |
| Fesoterodine | Percent Change From Baseline of UUI Episodes Per 24 Hours | Week 1 (n=442, 911, 899) | -50.0 percent change |
| Fesoterodine | Percent Change From Baseline of UUI Episodes Per 24 Hours | Week 12 [LOCF] (n=448, 926, 908) | -100.0 percent change |
| Fesoterodine | Percent Change From Baseline of UUI Episodes Per 24 Hours | Week 4 [LOCF] (n=448, 922, 908) | -100.0 percent change |
Comparison: Treatment difference fesoterodine vs placebo at Week 1.p-value: 0.0012ANCOVA
Comparison: Treatment difference Tolterodine ER vs placebo at Week 1.p-value: 0.0205ANCOVA
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: 0.0038ANCOVA
Comparison: Treatment difference Tolterodine ER vs Fesoterodine at Week 4.p-value: 0.0219ANCOVA
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: 0.0805ANCOVA
Comparison: Treatment difference Tolterodine ER vs Fesoterodine at Week 12.p-value: 0.0093ANCOVA
Post Hoc
Post-hoc Adverse Events (AEs)
An adverse event is any untoward medical occurrence in a clinical investigation in which the participant was administered a product or medical device; the event does not necessarily need to have a causal relationship with the treatment or usage.
Time frame: Baseline up to Week 12
Population: Safety population included all participants who were randomized and received at least 1 dose of study treatment. N=number of participants with AEs noted in other unreviewed medical chart records as performed at other departments during the clinical trial but were not included as AEs in Case Report Forms; reported post-hoc.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Post-hoc Adverse Events (AEs) | Abdominal bloating | 0 events |
| Placebo | Post-hoc Adverse Events (AEs) | Fingers tingling | 0 events |
| Placebo | Post-hoc Adverse Events (AEs) | Finger numbness | 0 events |
| Placebo | Post-hoc Adverse Events (AEs) | Hypertension | 0 events |
| Placebo | Post-hoc Adverse Events (AEs) | Tina pedis | 0 events |
| Placebo | Post-hoc Adverse Events (AEs) | Diabetes mellitus | 0 events |
| Placebo | Post-hoc Adverse Events (AEs) | Abdominal distension and discomfort | 0 events |
| Placebo | Post-hoc Adverse Events (AEs) | Tingling sensation/decreased sensation of fingers | 0 events |
| Placebo | Post-hoc Adverse Events (AEs) | Dyspepsia | 0 events |
| Placebo | Post-hoc Adverse Events (AEs) | Constipation | 1 events |
| Tolterodine ER | Post-hoc Adverse Events (AEs) | Dyspepsia | 1 events |
| Tolterodine ER | Post-hoc Adverse Events (AEs) | Constipation | 0 events |
| Tolterodine ER | Post-hoc Adverse Events (AEs) | Diabetes mellitus | 2 events |
| Tolterodine ER | Post-hoc Adverse Events (AEs) | Fingers tingling | 1 events |
| Tolterodine ER | Post-hoc Adverse Events (AEs) | Tingling sensation/decreased sensation of fingers | 1 events |
| Tolterodine ER | Post-hoc Adverse Events (AEs) | Finger numbness | 1 events |
| Tolterodine ER | Post-hoc Adverse Events (AEs) | Abdominal distension and discomfort | 1 events |
| Tolterodine ER | Post-hoc Adverse Events (AEs) | Tina pedis | 1 events |
| Tolterodine ER | Post-hoc Adverse Events (AEs) | Abdominal bloating | 1 events |
| Tolterodine ER | Post-hoc Adverse Events (AEs) | Hypertension | 2 events |