Trial Outcomes & Findings for Clinical Trial to Evaluate the Efficacy and Safety of Fesoterodine in Comparison to Tolterodine Extended Release(ER)in Patients With Overactive Bladder. (NCT NCT00611026)

Last Updated: 2011-02-02

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2417 participants

Primary outcome timeframe

Baseline, Week 12

Results posted on

2011-02-02

Participant Flow

Participants with urgency incontinence Overactive Bladder (OAB) symptoms who met all entrance criteria were randomized to the double-blind treatment period.

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.

Participant milestones

Participant milestones
Measure	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.	Tolterodine ER Capsules 4 mg PO QD for 12 weeks. Tolterodine Extended Release (ER).	Fesoterodine Tablets 4 mg PO QD for 1 week followed by a forced dose escalation to 8 mg PO QD for 11 weeks.
Randomized to Double-blind Treatment STARTED	480	974	963
Randomized to Double-blind Treatment COMPLETED	478	973	960
Randomized to Double-blind Treatment NOT COMPLETED	2	1	3
Double-blind Treatment Period STARTED	478	973	960
Double-blind Treatment Period COMPLETED	431	885	862
Double-blind Treatment Period NOT COMPLETED	47	88	98

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	Tolterodine ER Capsules 4 mg PO QD for 12 weeks. Tolterodine Extended Release (ER).	Fesoterodine Tablets 4 mg PO QD for 1 week followed by a forced dose escalation to 8 mg PO QD for 11 weeks.
Randomized to Double-blind Treatment Not treated	2	1	3
Double-blind Treatment Period Death	1	0	0
Double-blind Treatment Period Adverse Event	9	28	46
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 Withdrawal by Subject	7	19	16
Double-blind Treatment Period Other	13	20	18

Baseline Characteristics

Clinical Trial to Evaluate the Efficacy and Safety of Fesoterodine in Comparison to Tolterodine Extended Release(ER)in Patients With Overactive Bladder.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=478 Participants 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.	Tolterodine ER n=973 Participants Capsules 4 mg PO QD for 12 weeks. Tolterodine Extended Release (ER).	Fesoterodine n=960 Participants Tablets 4 mg PO QD for 1 week followed by a forced dose escalation to 8 mg PO QD for 11 weeks.	Total n=2411 Participants Total of all reporting groups
Age, Customized Between 18 and 44 years	70 participants n=5 Participants	157 participants n=7 Participants	156 participants n=5 Participants	383 participants n=4 Participants
Age, Customized Between 45 and 64 years	214 participants n=5 Participants	462 participants n=7 Participants	474 participants n=5 Participants	1150 participants n=4 Participants
Age, Customized ≥65 years	194 participants n=5 Participants	354 participants n=7 Participants	330 participants n=5 Participants	878 participants n=4 Participants
Sex: Female, Male Female	410 Participants n=5 Participants	818 Participants n=7 Participants	816 Participants n=5 Participants	2044 Participants n=4 Participants
Sex: Female, Male Male	68 Participants n=5 Participants	155 Participants n=7 Participants	144 Participants n=5 Participants	367 Participants n=4 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=448 Participants 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.	Tolterodine ER n=926 Participants Capsules 4 mg PO QD for 12 weeks. Tolterodine Extended Release (ER).	Fesoterodine n=908 Participants Tablets 4 mg PO QD for 1 week followed by a forced dose escalation to 8 mg PO QD for 11 weeks.
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	-1.74 episodes per 24 hours Standard Error 0.06	-1.95 episodes per 24 hours Standard Error 0.05

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=452 Participants 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.	Tolterodine ER n=930 Participants Capsules 4 mg PO QD for 12 weeks. Tolterodine Extended Release (ER).	Fesoterodine n=912 Participants Tablets 4 mg PO QD for 1 week followed by a forced dose escalation to 8 mg PO QD for 11 weeks.
Change From Baseline in Mean Voided Volume Per Micturition Week 1 (n=447, 917, 895)	9.80 mL Standard Error 1.92	15.65 mL Standard Error 1.43	18.63 mL Standard Error 1.55
Change From Baseline in Mean Voided Volume Per Micturition Week 4 [LOCF] (n=452, 927, 909)	14.27 mL Standard Error 2.28	26.43 mL Standard Error 1.76	32.26 mL Standard Error 1.94
Change From Baseline in Mean Voided Volume Per Micturition Week 12 [LOCF] (n=452, 930, 912)	17.34 mL Standard Error 2.40	28.43 mL Standard Error 1.82	34.47 mL Standard Error 2.06

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=454 Participants 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.	Tolterodine ER n=935 Participants Capsules 4 mg PO QD for 12 weeks. Tolterodine Extended Release (ER).	Fesoterodine n=916 Participants Tablets 4 mg PO QD for 1 week followed by a forced dose escalation to 8 mg PO QD for 11 weeks.
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	-1.0 micturitions per 24 hours Standard Error 0.1	-1.0 micturitions per 24 hours Standard Error 0.1
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	-1.8 micturitions per 24 hours Standard Error 0.1	-2.1 micturitions per 24 hours Standard Error 0.1
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	-2.3 micturitions per 24 hours Standard Error 0.1	-2.6 micturitions per 24 hours Standard Error 0.1

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Placebo n=454 Participants 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.	Tolterodine ER n=935 Participants Capsules 4 mg PO QD for 12 weeks. Tolterodine Extended Release (ER).	Fesoterodine n=916 Participants Tablets 4 mg PO QD for 1 week followed by a forced dose escalation to 8 mg PO QD for 11 weeks.
Percent Change From Baseline of Micturitions Per 24 Hours Week 4 [LOCF] (n=454, 931, 916)	-13.4 percent change Interval -64.4 to 118.8	-16.7 percent change Interval -67.9 to 64.0	-18.9 percent change Interval -68.8 to 96.2
Percent Change From Baseline of Micturitions Per 24 Hours Week 1 (n=448, 921, 908)	-7.1 percent change Interval -70.6 to 53.6	-9.4 percent change Interval -64.3 to 74.2	-9.0 percent change Interval -61.9 to 89.3
Percent Change From Baseline of Micturitions Per 24 Hours Week 12 [LOCF] (n=454, 935, 916)	-18.2 percent change Interval -66.7 to 118.8	-20.8 percent change Interval -67.5 to 70.8	-23.5 percent change Interval -75.3 to 64.3

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=445 Participants 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.	Tolterodine ER n=899 Participants Capsules 4 mg PO QD for 12 weeks. Tolterodine Extended Release (ER).	Fesoterodine n=892 Participants Tablets 4 mg PO QD for 1 week followed by a forced dose escalation to 8 mg PO QD for 11 weeks.
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	-0.3 nocturnal micturitions per 24 hours Standard Error 0.0	-0.3 nocturnal micturitions per 24 hours Standard Error 0.0
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	-0.5 nocturnal micturitions per 24 hours Standard Error 0.0	-0.5 nocturnal micturitions per 24 hours Standard Error 0.0
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	-0.6 nocturnal micturitions per 24 hours Standard Error 0.0	-0.7 nocturnal micturitions per 24 hours Standard Error 0.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=445 Participants 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.	Tolterodine ER n=899 Participants Capsules 4 mg PO QD for 12 weeks. Tolterodine Extended Release (ER).	Fesoterodine n=892 Participants Tablets 4 mg PO QD for 1 week followed by a forced dose escalation to 8 mg PO QD for 11 weeks.
Percent Change From Baseline of Nocturnal Micturitions Per 24 Hours Week 1 (n=432, 879, 871)	-7.7 percent change Interval -100.0 to 500.0	-14.3 percent change Interval -100.0 to 500.0	-12.5 percent change Interval -100.0 to 800.0
Percent Change From Baseline of Nocturnal Micturitions Per 24 Hours Week 4 [LOCF] (n=437, 888, 879)	-20.0 percent change Interval -100.0 to 600.0	-25.0 percent change Interval -100.0 to 400.0	-25.0 percent change Interval -100.0 to 1600.0
Percent Change From Baseline of Nocturnal Micturitions Per 24 Hours Week 12 [LOCF] (n=437, 892, 879)	-27.3 percent change Interval -100.0 to 800.0	-33.3 percent change Interval -100.0 to 350.0	-33.3 percent change Interval -100.0 to 500.0

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Placebo n=456 Participants 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.	Tolterodine ER n=932 Participants Capsules 4 mg PO QD for 12 weeks. Tolterodine Extended Release (ER).	Fesoterodine n=920 Participants Tablets 4 mg PO QD for 1 week followed by a forced dose escalation to 8 mg PO QD for 11 weeks.
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	-0.95 episodes per 24 hours Standard Error 0.05	-1.03 episodes per 24 hours Standard Error 0.05
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	-1.52 episodes per 24 hours Standard Error 0.05	-1.68 episodes per 24 hours Standard Error 0.05

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=456 Participants 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.	Tolterodine ER n=932 Participants Capsules 4 mg PO QD for 12 weeks. Tolterodine Extended Release (ER).	Fesoterodine n=920 Participants Tablets 4 mg PO QD for 1 week followed by a forced dose escalation to 8 mg PO QD for 11 weeks.
Percent Change From Baseline of UUI Episodes Per 24 Hours Week 1 (n=442, 911, 899)	-40.8 percent change Interval -100.0 to 966.7	-50.0 percent change Interval -100.0 to 366.7	-50.0 percent change Interval -100.0 to 633.3
Percent Change From Baseline of UUI Episodes Per 24 Hours Week 4 [LOCF] (n=448, 922, 908)	-75.0 percent change Interval -100.0 to 1000.0	-88.9 percent change Interval -100.0 to 900.0	-100.0 percent change Interval -100.0 to 666.7
Percent Change From Baseline of UUI Episodes Per 24 Hours Week 12 [LOCF] (n=448, 926, 908)	-100.0 percent change Interval -100.0 to 612.5	-100.0 percent change Interval -100.0 to 687.5	-100.0 percent change Interval -100.0 to 500.0

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Placebo n=461 Participants 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.	Tolterodine ER n=940 Participants Capsules 4 mg PO QD for 12 weeks. Tolterodine Extended Release (ER).	Fesoterodine n=928 Participants Tablets 4 mg PO QD for 1 week followed by a forced dose escalation to 8 mg PO QD for 11 weeks.
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	-1.0 episodes per 24 hours Standard Error 0.1	-1.2 episodes per 24 hours Standard Error 0.2
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	-2.5 episodes per 24 hours Standard Error 0.2	-3.1 episodes per 24 hours Standard Error 0.2
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	-3.5 episodes per 24 hours Standard Error 0.2	-4.2 episodes per 24 hours Standard Error 0.2

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=461 Participants 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.	Tolterodine ER n=940 Participants Capsules 4 mg PO QD for 12 weeks. Tolterodine Extended Release (ER).	Fesoterodine n=928 Participants Tablets 4 mg PO QD for 1 week followed by a forced dose escalation to 8 mg PO QD for 11 weeks.
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 Interval -100.0 to 385.7	-12.0 percent change Interval -100.0 to 325.0	-11.8 percent change Interval -100.0 to 433.3
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 Interval -100.0 to 457.1	-26.3 percent change Interval -100.0 to 350.0	-32.1 percent change Interval -100.0 to 433.3
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 Interval -100.0 to 385.7	-37.5 percent change Interval -100.0 to 475.0	-45.5 percent change Interval -100.0 to 266.7

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Placebo n=460 Participants 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.	Tolterodine ER n=937 Participants Capsules 4 mg PO QD for 12 weeks. Tolterodine Extended Release (ER).	Fesoterodine n=924 Participants Tablets 4 mg PO QD for 1 week followed by a forced dose escalation to 8 mg PO QD for 11 weeks.
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	-1.34 severe urgency episodes per 24 hours Standard Error 0.10	-1.58 severe urgency episodes per 24 hours Standard Error 0.11
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	-2.71 severe urgency episodes per 24 hours Standard Error 0.12	-3.21 severe urgency episodes per 24 hours Standard Error 0.12
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	-3.39 severe urgency episodes per 24 hours Standard Error 0.13	-4.08 severe urgency episodes per 24 hours Standard Error 0.13

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Placebo n=460 Participants 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.	Tolterodine ER n=937 Participants Capsules 4 mg PO QD for 12 weeks. Tolterodine Extended Release (ER).	Fesoterodine n=924 Participants Tablets 4 mg PO QD for 1 week followed by a forced dose escalation to 8 mg PO QD for 11 weeks.
Percent Change From Baseline of Severe Urgency Episodes Per 24 Hours Week 1 (n=446, 915, 902)	-19.7 percent change Interval -100.0 to 575.0	-24.1 percent change Interval -100.0 to 500.0	-25.0 percent change Interval -100.0 to 475.0
Percent Change From Baseline of Severe Urgency Episodes Per 24 Hours Week 4 [LOCF] (n=452, 926, 911)	-41.7 percent change Interval -100.0 to 533.3	-55.6 percent change Interval -100.0 to 800.0	-61.1 percent change Interval -100.0 to 433.3
Percent Change From Baseline of Severe Urgency Episodes Per 24 Hours Week 12 [LOCF] (n=452, 930, 911)	-61.0 percent change Interval -100.0 to 1850.0	-69.2 percent change Interval -100.0 to 600.0	-79.3 percent change Interval -100.0 to 440.0

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Placebo n=453 Participants 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.	Tolterodine ER n=933 Participants Capsules 4 mg PO QD for 12 weeks. Tolterodine Extended Release (ER).	Fesoterodine n=915 Participants Tablets 4 mg PO QD for 1 week followed by a forced dose escalation to 8 mg PO QD for 11 weeks.
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 0.0	-0.2 scores on a scale Standard Error 0.0	-0.2 scores on a scale Standard Error 0.0
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 0.0	-0.4 scores on a scale Standard Error 0.0	-0.5 scores on a scale Standard Error 0.0
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 0.0	-0.6 scores on a scale Standard Error 0.0	-0.7 scores on a scale Standard Error 0.0

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Placebo n=453 Participants 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.	Tolterodine ER n=933 Participants Capsules 4 mg PO QD for 12 weeks. Tolterodine Extended Release (ER).	Fesoterodine n=915 Participants Tablets 4 mg PO QD for 1 week followed by a forced dose escalation to 8 mg PO QD for 11 weeks.
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	-4.8 scores on a scale Standard Error 0.5	-5.5 scores on a scale Standard Error 0.5
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	-10.1 scores on a scale Standard Error 0.6	-12.0 scores on a scale Standard Error 0.6
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	-13.2 scores on a scale Standard Error 0.6	-15.6 scores on a scale Standard Error 0.6

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Placebo n=448 Participants 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.	Tolterodine ER n=926 Participants Capsules 4 mg PO QD for 12 weeks. Tolterodine Extended Release (ER).	Fesoterodine n=908 Participants Tablets 4 mg PO QD for 1 week followed by a forced dose escalation to 8 mg PO QD for 11 weeks.
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	46.7 percentage of participants	51.1 percentage of participants
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	24.5 percentage of participants	25.1 percentage of participants
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	58.1 percentage of participants	63.2 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=455 Participants 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.	Tolterodine ER n=937 Participants Capsules 4 mg PO QD for 12 weeks. Tolterodine Extended Release (ER).	Fesoterodine n=918 Participants Tablets 4 mg PO QD for 1 week followed by a forced dose escalation to 8 mg PO QD for 11 weeks.
Change From Baseline in Patient Perception of Bladder Condition (PPBC) Week 1 (n=452, 931, 913) ≥2 points improvement	43 participants	138 participants	144 participants
Change From Baseline in Patient Perception of Bladder Condition (PPBC) Week 1: 1-point improvement	144 participants	278 participants	280 participants
Change From Baseline in Patient Perception of Bladder Condition (PPBC) Week 1: no change	210 participants	434 participants	428 participants
Change From Baseline in Patient Perception of Bladder Condition (PPBC) Week 1: deterioration	55 participants	81 participants	61 participants
Change From Baseline in Patient Perception of Bladder Condition (PPBC) Week 4 (n=455, 937, 918) ≥2 points improvement	111 participants	290 participants	334 participants
Change From Baseline in Patient Perception of Bladder Condition (PPBC) Week 4: 1-point improvement	124 participants	298 participants	280 participants
Change From Baseline in Patient Perception of Bladder Condition (PPBC) Week 4: no change	172 participants	285 participants	250 participants
Change From Baseline in Patient Perception of Bladder Condition (PPBC) Week 4: deterioration	48 participants	64 participants	54 participants
Change From Baseline in Patient Perception of Bladder Condition (PPBC) Week 12 (n=455, 937, 918) ≥2 points improvement	166 participants	379 participants	440 participants
Change From Baseline in Patient Perception of Bladder Condition (PPBC) Week 12: 1-point improvement	106 participants	250 participants	236 participants
Change From Baseline in Patient Perception of Bladder Condition (PPBC) Week 12: no change	133 participants	249 participants	189 participants
Change From Baseline in Patient Perception of Bladder Condition (PPBC) Week 12: deterioration	50 participants	59 participants	53 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=455 Participants 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.	Tolterodine ER n=938 Participants Capsules 4 mg PO QD for 12 weeks. Tolterodine Extended Release (ER).	Fesoterodine n=918 Participants Tablets 4 mg PO QD for 1 week followed by a forced dose escalation to 8 mg PO QD for 11 weeks.
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	264 participants	267 participants
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	619 participants	609 participants
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	49 participants	37 participants
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	376 participants	421 participants
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	511 participants	467 participants
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	51 participants	30 participants
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	440 participants	495 participants
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	455 participants	393 participants
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	43 participants	30 participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=436 Participants 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.	Tolterodine ER n=897 Participants Capsules 4 mg PO QD for 12 weeks. Tolterodine Extended Release (ER).	Fesoterodine n=876 Participants Tablets 4 mg PO QD for 1 week followed by a forced dose escalation to 8 mg PO QD for 11 weeks.
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	-24.3 scores on a scale Standard Error 1.0	-28.9 scores on a scale Standard Error 1.1

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=435 Participants 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.	Tolterodine ER n=894 Participants Capsules 4 mg PO QD for 12 weeks. Tolterodine Extended Release (ER).	Fesoterodine n=875 Participants Tablets 4 mg PO QD for 1 week followed by a forced dose escalation to 8 mg PO QD for 11 weeks.
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	19.5 scores on a scale Standard Error 1.0	22.9 scores on a scale Standard Error 1.0
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	22.5 scores on a scale Standard Error 1.1	26.8 scores on a scale Standard Error 1.1
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	22.0 scores on a scale Standard Error 1.1	25.9 scores on a scale Standard Error 1.2
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	18.7 scores on a scale Standard Error 1.1	21.0 scores on a scale Standard Error 1.1
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 1.0	12.0 scores on a scale Standard Error 0.8	13.9 scores on a scale Standard Error 0.8

POST_HOC outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=1 Participants 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.	Tolterodine ER n=1 Participants Capsules 4 mg PO QD for 12 weeks. Tolterodine Extended Release (ER).	Fesoterodine Tablets 4 mg PO QD for 1 week followed by a forced dose escalation to 8 mg PO QD for 11 weeks.
Post-hoc Adverse Events (AEs) Constipation	1 events	0 events	—
Post-hoc Adverse Events (AEs) Fingers tingling	0 events	1 events	—
Post-hoc Adverse Events (AEs) Finger numbness	0 events	1 events	—
Post-hoc Adverse Events (AEs) Hypertension	0 events	2 events	—
Post-hoc Adverse Events (AEs) Diabetes mellitus	0 events	2 events	—
Post-hoc Adverse Events (AEs) Abdominal distension and discomfort	0 events	1 events	—
Post-hoc Adverse Events (AEs) Tina pedis	0 events	1 events	—
Post-hoc Adverse Events (AEs) Tingling sensation/decreased sensation of fingers	0 events	1 events	—
Post-hoc Adverse Events (AEs) Dyspepsia	0 events	1 events	—
Post-hoc Adverse Events (AEs) Abdominal bloating	0 events	1 events	—

Adverse Events

Placebo

Serious events: 8 serious events

Other events: 83 other events

Deaths: 0 deaths

Tolterodine ER

Serious events: 6 serious events

Other events: 261 other events

Deaths: 0 deaths

Fesoterodine

Serious events: 13 serious events

Other events: 375 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=478 participants at risk 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.	Tolterodine ER n=973 participants at risk Capsules 4 mg PO QD for 12 weeks. Tolterodine Extended Release (ER).	Fesoterodine n=960 participants at risk Tablets 4 mg PO QD for 1 week followed by a forced dose escalation to 8 mg PO QD for 11 weeks.
Gastrointestinal disorders Constipation	1.5% 7/478 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	3.1% 30/973 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	4.4% 42/960 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.
Gastrointestinal disorders Diarrhoea	0.63% 3/478 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	1.1% 11/973 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	1.1% 11/960 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.
Gastrointestinal disorders Dry mouth	5.4% 26/478 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	13.4% 130/973 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	27.6% 265/960 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.
Gastrointestinal disorders Dyspepsia	0.42% 2/478 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	1.0% 10/973 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	2.2% 21/960 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.
Gastrointestinal disorders Nausea	0.63% 3/478 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	1.3% 13/973 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	1.1% 11/960 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.
General disorders Oedema peripheral	1.0% 5/478 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	1.4% 14/973 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	0.42% 4/960 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.
Infections and infestations Bronchitis	1.3% 6/478 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	1.0% 10/973 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	0.31% 3/960 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.
Infections and infestations Influenza	0.21% 1/478 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	1.2% 12/973 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	0.52% 5/960 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.
Infections and infestations Nasopharyngitis	1.3% 6/478 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	0.92% 9/973 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	0.83% 8/960 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.
Infections and infestations Sinusitis	0.42% 2/478 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	1.1% 11/973 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	0.42% 4/960 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.
Infections and infestations Urinary tract infection	1.0% 5/478 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	1.2% 12/973 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	1.5% 14/960 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.
Musculoskeletal and connective tissue disorders Back pain	1.3% 6/478 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	0.92% 9/973 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	0.83% 8/960 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.
Nervous system disorders Headache	1.3% 6/478 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	2.1% 20/973 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	2.8% 27/960 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.
Renal and urinary disorders Dysuria	0.42% 2/478 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	0.82% 8/973 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	1.0% 10/960 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.
Renal and urinary disorders Polyuria	2.1% 10/478 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	2.5% 24/973 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	3.0% 29/960 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.
Respiratory, thoracic and mediastinal disorders Cough	0.63% 3/478 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	0.41% 4/973 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	1.2% 12/960 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.
Respiratory, thoracic and mediastinal disorders Dry throat	0.00% 0/478 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	0.21% 2/973 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	1.1% 11/960 An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.