PhRMA Web Synopsis
Protocol A0221005 – 13 August 2009 – Final

PFIZER INC.
These results are supplied for informational purposes only.
Prescribing decisions should be made based on the approved package insert.
For publications based on this study, see associated bibliography.
PROPRIETARY DRUG NAME®/GENERIC DRUG NAME: Toviaz® / Fesoterodine
THERAPEUTIC AREA AND FDA APPROVED INDICATIONS: See USPI.
NATIONAL CLINICAL TRIAL NO.: NCT 00561951
PROTOCOL NO.: A0221005

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PROTOCOL TITLE: A 12-Week, Randomized, Double-Blind, Placebo-Controlled,
Parallel-Group, Multicenter, Dose-Finding Study to Evaluate the Efficacy, Tolerability and
Safety of Fesoterodine in Comparison to Placebo in Patients with Overactive Bladder
Study Center(s): Subjects were randomized at 69 centers (Hong Kong 3 centers, Japan 55
centers, Korea 5 centers, Taiwan 6 centers). One center in Taiwan did not enroll subjects and1 center in Japan did not randomize subjects.
Study Initiation and Completion Dates: 27 November 2007 to 15 January 2009
Phase of Development: Phase 2
Study Objective(s):The primary objective of the study was to assess the efficacy of fesoterodine 4 mg and 8 mg
as compared to placebo in subjects with Overactive Bladder (OAB) syndrome after 12 weeks
of treatment and to determine the recommended dose in subjects with OAB.
The secondary objectives were the following: to assess the safety and tolerability offesoterodine 4 mg and 8 mg as compared to placebo in subjects with OAB after 12 weeks oftreatment; to investigate pharmacokinetics of 5-HMT, the active metabolite of fesoterodine inpatients with OAB who take fesoterodine 4 mg and 8 mg.
Comparisons of the results for efficacy and safety between this study and previous studies
conducted to support registration in the US and Europe were also planned.
METHODS
Study Design: This was a 12-week, multicenter, randomized, double-blind, placebocontrolled, parallel-group, dose-finding study. The trial consisted of a 2-week single-blind
placebo run-in period and a 12-week double-blind treatment period and required a total of 6
in-clinic visits (Figure S1).

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Subjects were initially screened at Visit 1 (Screening/Enrollment visit). Eligible subjects
were enrolled at the same visit into the run-in period and received single-blind placebo for 2
weeks. The subject completed a 3-day micturition diary for 3 consecutive days during the 7days prior to Visit 2 (Randomization/Baseline visit). The diary captured each micturition,
including urgency urinary incontinence (UUI) episodes and urgency episodes, along with thecorresponding time of the events. Each subject also measured and recorded the urine voided
volume of any 1 day and the first micturition of the next day during 3-day diary period.
At Visit 2, the diary data and screening laboratory data were checked against the
randomization criteria. Only OAB subjects with UUI defined as subjects with 3 UUI
episodes during the 3-day diary period prior to randomization, who met the criteria wererandomized to one of three treatment arms (fesoterodine 4 mg, fesoterodine 8 mg or placebo)in a 1:1:1 ratio. Randomized subjects received the assigned double-blind treatment for 12
weeks.
Placebo

Figure S1Fesoterodine 4 mg QD

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PlaceboFesoterodine 8 mg QD

Day -14+/- 3 days

Visit 1
Screening/
Enrollment

Day14+/- 3 days

Day28+/- 3 days

Day56+/- 3 days

Day84+/- 3 days

Visit 3
Visit 2
Randomization/ Week 2
Baseline

Visit 4
Week 4

Visit 5
Week 8

Visit 6
Week 12/Endof Treatment

Day0

Number of Subjects (Planned and Analyzed): In this trial, 900 subjects were required forthe analysis population. Six hundred subjects in Japan and 300 subjects in other Asian
countries were planned to be enrolled. In total 951 subjects were analyzed for safety and 929
subjects met the required criteria to contribute to the efficacy analysis.
Diagnosis and Main Criteria for Inclusion: Adult males and females with a 6-month
history of symptoms or signs of OAB syndrome with urinary urgency and increased urinary
frequency were included in this study. Subjects had symptoms of UUI for 1 month prior to
Visit 1. At least 3 UUI episodes documented during the 3-day micturition diary period and8 micturitions per 24 hours confirmed on each day of the 3-day micturition diary periodprior to Visit 2 were required for participation in the study.
Study Treatment: Fesoterodine 4 mg, 8 mg and a matching placebo were used.
Fesoterodine placebo tablets were indistinguishable in appearance from fesoterodine 4 mg
and 8 mg tablets. Subjects received one single blind fesoterodine placebo tablet orally for 2
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Protocol A0221005 – 13 August 2009 – Final

weeks from the morning of the day after Visit 1 with water every morning with or without
food. Eligible subjects then received one double blind fesoterodine 4 mg tablet, 8 mg tablet,or placebo tablet orally from the morning of the day after Visit 2 with water every morningwith or without food for a total of 12 weeks.
Efficacy Evaluations: Subjects completed a micturition diary for 3 consecutive days during
the 7 days preceding each visit. In this diary, “a day” was defined as the period between thetime subjects woke up in the morning to actively start the day through the time the subjects
woke up the next morning. Subjects were also required to complete questionnaires including
KHQ, OAB-q, and PPBC at Visits 2 and 6.

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Pharmacokinetic Evaluations: For pharmacokinetic analysis, blood samples (4 mL) werecollected in tubes containing lithium heparin at Visits 4 and 6. At each visit, 2 blood samples
were taken at least 30 minutes apart. The investigator was to confirm the dosing time of the
3 administrations immediately prior to blood sampling at each visit.
Safety Evaluations: Adverse events were recorded on the case report form (CRF) from thetime the subject took at least one dose of study treatment after randomization through the last
subject visit. Serious adverse events required immediate notification to the sponsor or its
designated representative beginning from the time that the subject provided informed
consent, through and including 28 calendar days after the last administration of the study
treatment. Clinical laboratory tests were performed by the central laboratory at Visits 1, 4,
and 6. Blood pressure and pulse rate were recorded at all clinic visits. Twelve-leadelectrocardiogram and residual urine volume measurements were performed at Visits 1, 2, 4,
and 6.
Statistical Methods: The full analysis set (FAS) was the primary analysis set for theefficacy analyses. The FAS included all subjects who took at least one dose of study drug
after randomization and had efficacy observations at both baseline and post baseline. The
primary endpoint was change from baseline in mean number of UUI episodes per 24 hours at
Week 12. The comparisons of fesoterodine 8 mg with placebo and fesoterodine 4 mg withplacebo were tested by using analysis of covariance (ANCOVA) model with the treatmentgroup, region (Japan, Korea, Taiwan and Hong Kong) as fixed effects and baseline values asa covariate. A closed testing procedure was used in order to control the probability of a type1 error. Significance level was =0.05. Last observation carried forward (LOCF) was used
to impute missing data at Week 12 for the FAS analysis. The same analyses were performed
for change from baseline in mean number of micturitions, urgency episodes, incontinence
episodes, and night-time micturitions per 24 hours at Week 12. The descriptive statistics forthe change from baseline to Week 12 were performed the primary endpoint and all secondary
endpoints including micturition diary, KHQ, OAB-q, and PPBC.
The pharmacokinetic analysis set consisted of the safety set subjects who had
pharmacokinetic data recorded. For each subject, 4 plasma samples to measure plasma 5HMT concentration were obtained during the trial. Two samples were taken at each of thefollowing visits: Visit 4 (Day 28 ± 3), and Visit 6/early termination (Day 84 ± 3). Allconcentration data collected during the trial were listed. Population pharmacokinetic analysisof 5-HMT was planned.
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The safety analysis set included all subjects who took at least one dose of study drug after
randomization. The safety assessment was based on the incidence, severity and nature oftreatment emergent adverse events recorded during the treatment period. However, subjects
who were not randomized but received the randomized study drug were included in thesafety analysis set, if they have post-dosing safety data. Safety data were evaluated using
descriptive statistics. Standard output tables were produced for adverse events, vital signs,
ECG data and lab data in accordance with Pfizer Data Standards (PDS). The Medical
Dictionary for Regulatory Activities (MedDRA), version 11.1 was used for coding of adverse
events.
The analysis plan and report for comparisons of the results for efficacy and safety between
this study and previous studies conducted to support registration in the US and Europe which
was one of the objectives of this study were generated separately from this report.

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RESULTS
Subject Disposition and Demography: A total of 1232 subjects were enrolled and entered
the placebo run-in period. Out of them, 951 subjects were assigned to the double-blind
treatment. All 951 subjects were treated. There was 1 subject (ID 10051026) who was not
randomized but took the study drugs for the double-blind treatment period. This subject wascounted as being assigned to the double-blind treatment and was also included in the safety
analysis set. All other 950 subjects were randomized (Table S1).

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Table S1. Subject Disposition and Subjects Evaluated [Number (%) of Subjects]
Enrolled in placebo run-in= 1232
Assigned to double-blind treatmenta
TreatedCompleted study
Discontinued study
Adverse eventsb
Lack of efficacy
Lost to follow-up
Subject no longer willing to participate in study
Other
Analyzed for efficacy
FAS
Analyzed for pharmacokinetics
Analyzed for safety
Adverse events
Laboratory data

PlaceboFesoterodine 4 mg

Fesoterodine 8 mg

318
318
285 (89.6)
33 (10.4)
12 (3.8)
5 (1.6)
1 (0.3)10 (3.1)
5 (1.6)320320
286 (89.4)
34 (10.6)
15 (4.7)
3 (0.9)1 (0.3)9 (2.8)6c (1.9)313
313
281 (89.8)
32 (10.2)
15 (4.8)
2 (0.6)0
10 (3.2)
5 (1.6)309 (97.2)
312 (98.1)

314 (98.1)
312 (97.5)

306 (97.8)
310 (99.0)

318 (100.0)
315 (99.1)

320 (100.0)
314 (98.1)

313 (100.0)
312 (99.7)

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aIncluded the subjects who were randomized and took at least 1 dose of study drug and 1 subject in the placebogroup who was not randomized but took the study drugs for the double-blind treatment period during the run-in
period due to being wrongly dispensed.
bConsisted of subjects who discontinued due to no treatment emergent adverse event (1 subject each in alltreatment groups) and treatment emergent adverse event.
c
One subject (fesoterodine 4 mg) who met a withdrawal criterion was counted as discontinuation due to ‘Other
reason’. This event was also reported as treatment emergent adverse event (ie. electrocardiogram QT
prolonged). Therefore, the study drug action for this adverse event was reported as permanently discontinued.

All demographic characteristics were comparable across the 3 treatment groups (Table S2)

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Table S2. Demographic Characteristics in the Safety Analysis Set [Number (%) of
Subjects]
Sex [n (%)]
Male
FemaleAge (years)
<18
18-44
45-64
65
Mean (SD)
Range
Race [n (%)]
AsianRegion [n (%)]
Japan
Korea
TaiwanHong Kong
Weight (kg)
Mean (SD)
Range
Height (cm)Mean (SD)
Range
Body Mass Index
Mean (SD)
Range

PlaceboFesoterodine 4 mg

Fesoterodine 8 mg

Total

318
67 (21.1)
251 (78.9)

320
69 (21.6)
251 (78.4)

313
58 (18.5)
255 (81.5)

951
194 (20.4)
757 (79.6)

062 (19.5)
165 (51.9)
91 (28.6)
56.7 (13.5)
20-88

073 (22.8)
144 (45.0)
103 (32.2)
57.2 (14.2)
21-86

0
41 (13.1)
155 (49.5)
117 (37.4)
58.8 (13.4)
20-87

0
176 (18.5)
464 (48.8)
311 (32.7)
57.6 (13.7)
20-88

318 (100.0)

320 (100.0)

313 (100.0)

951 (100.0)

248 (78.0)
45 (14.2)
21 (6.6)
4 (1.3)250 (78.1)
46 (14.4)
21 (6.6)
3 (0.9)249 (79.6)
44 (14.1)
19 (6.1)
1 (0.3)747 (78.5)
135 (14.2)
61 (6.4)
8 (0.8)57.6 (10.6)
34.0-104.0

57.2 (10.4)
34.7-93.5

57.9 (10.6)
31.2-107.0

57.6 (10.5)
31.2-107.0

157.2 (8.3)
137.0-186.1

158.1 (8.0)
137.0-177.8

156.1 (7.5)
133.1-177.5

157.2 (8.0)
133.1-186.1

23.3 (3.8)
15.5-38.2

22.8 (3.5)
14.7-35.0

23.7 (3.9)
14.6-39.7

23.3 (3.7)
14.6-39.7

Descriptive summaries of the mean number of UUI episodes and micturitions per 24 hours atbaseline are provided in Table S3. Those values at baseline were comparable across the 3treatment groups.
Table S3. Mean Number of UUI Episodes and Micturitions per 24 hours at Baseline,
FAS

Number of UUI Episodes per 24 hours
Number of Micturitions per 24 hours

N
309
309

Placebo
Mean (SD)2.24 (1.872)
11.13 (2.494)

Fesoterodine 4 mg
N
Mean (SD)314
2.23 (1.814)
314
11.32 (2.576)

N
306
306

Fesoterodine 8 mg
Mean (SD)2.26 (1.788)
11.36 (2.560)

SD= standard deviation, UUI= urgency urinary incontinence.

Efficacy Results: Both fesoterodine 4 mg/day and 8 mg/day demonstrated statisticallysignificant decreases in the mean number of UUI episodes per 24 hours at Week 12 (primary
endpoint) compared to placebo. Dose dependent responses to fesoterodine 4 mg/day and8 mg/day were also observed (Table S4).

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Table S4. ANCOVA of Change from Baseline in Mean Number of UUI Episodes per
24 Hours at Week 12, FAS-LOCF
Treatment (N)Placebo (309)−1.01

95% CI for the
LS Mean(−1.31, −0.71)

Fesoterodine 4 mg (314)−1.35(−1.65, −1.05)

4 mg vs Placebo−0.34(−0.56, −0.13)

0.002

Fesoterodine 8 mg (306)−1.40(−1.70, −1.09)

8 mg vs Placebo−0.39(−0.60, −0.17)<0.001LS Mean―Treatment
difference―

95% CI for
the difference―

Contrast

p-valuea―

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ANCOVA=analysis of covariance, CI=confidence interval, FAS=full analysis set, LOCF=last observation
carried forward, LS=least squares, UUI= urgency urinary incontinence, vs=versus.
Baseline value for each subject was defined as a value of Week 0.
Analysis of covariance model with the treatment group, region as fixed effects and baseline values as acovariate was used.
a
The closed testing procedure was used in order to control the probability of a type 1 error. The significancelevel was 0.05 (2-sided).

Both fesoterodine 4 mg/day and 8 mg/day demonstrated statistically significant decreases in
the mean number of micturitions per 24 hours at Week 12 compared to placebo. Dosedependent responses to fesoterodine 4 mg/day and 8 mg/day were also observed. Numericalimprovements were observed with fesoterodine 4 mg/day and 8 mg/day in other secondary
micturition diary endpoints compared to placebo. Out of them, the mean numbers of urgency
and incontinence episodes per 24 hours at Week 12 were statistically significant (Table S5).
Fesoterodine 4 mg/day and 8 mg/day increased (improved) mean voided volume per
micturition in a dose-dependent manner during this study.

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Table S5. ANCOVA of Change from Baseline in Mean Number of Micturitions,
Urgency Episodes, Incontinence Episodes, and Night-Time Micturitions per
24 Hours at Week 12, FAS-LOCF
Treatment (N)Contrast

Treatment
difference

95% CI for thedifference

p-value a

LS Mean

95% CI for
the LS Mean

Placebo (309)−0.59(−1.08, −0.10)

―

―

―

―

Fesoterodine 4 mg (314)Fesoterodine 8 mg (306)

−1.15
−1.25

(−1.64, −0.67)(−1.75, −0.76)

4 mg vs Placebo
8 mg vs Placebo

−0.56
−0.66

(−0.91, −0.22)(−1.01, −0.32)

0.002<0.001

Urgency Episodes
Placebo (309)−1.00(−1.60, −0.40)

―

―

―

―

Fesoterodine 4 mg (314)−1.65(−2.25, −1.05)

4 mg vs Placebo−0.65(−1.07, −0.22)

0.003

Fesoterodine 8 mg (306)−1.66(−2.27, −1.05)

8 mg vs Placebo−0.66(−1.09, −0.23)

0.002

Incontinence Episodes
Placebo (309)−0.88(−1.22, −0.54)

―

―

―

―

Fesoterodine 4 mg (314)Fesoterodine 8 mg (306)

−1.27
−1.15

(−1.61, −0.93)(−1.50, −0.80)

4 mg vs Placebo
8 mg vs Placebo

−0.39
−0.27

(−0.63, −0.14)(−0.52, −0.03)

0.002
0.030

Night-Time Micturitions
Placebo (243)−0.18(−0.41, 0.06)

―

―

―

―

Fesoterodine 4 mg (256)
Fesoterodine 8 mg (257)

−0.21
−0.29

(−0.44, 0.02)(−0.52, −0.05)

4 mg vs Placebo
8 mg vs Placebo

−0.04
−0.11

(−0.18, 0.11)(−0.26, 0.03)

0.624
0.129

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Micturitions

ANCOVA=analysis of covariance, CI=confidence interval, FAS=full analysis set, LOCF=last observation
carried forward, LS=least squares, vs=versus.
Baseline value for each subject was defined as a value of Week 0.
Analysis of covariance model with the treatment group, region as fixed effects and baseline values as acovariate was used.
a
The significance level was 0.05 (2-sides).

In each domain of KHQ, subjects receiving fesoterodine demonstrated improvement frombaseline that was greater than that of placebo, except for general health perception. In eachdomain of OAB-q, the improvement in the symptom bother score was more marked in the
fesoterodine 4 and 8 mg groups than the placebo group. An improvement in all 4 HRQL
domains (coping, concern, sleep, and social) and total HRQL score was also more marked in
the fesoterodine 4 and 8 mg groups than the placebo group. The minimum PPBC score atbaseline was “some moderate problems, score 4” across the 3 treatment groups due to one of
the inclusion criteria. At Week 12, “some minor problems, score 3” or “some very minor
problems, score 2” or even “no problems at all, score 1” were found in 71.2% in the placebogroup, and in 77.7% and 78.1% in the fesoterodine 4 and 8 mg/day groups, respectively.
Pharmacokinetic Results: Population pharmacokinetic analysis results will be summarized
in a separate report.
Safety Results: Overall summary of adverse events is shown in Table S6.

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Table S6. Overall Summary of Treatment-Emergent Adverse Events

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Number of adverse events
All causality
Treatment-related
Number (%) of subjects
Adverse events
All causality
Treatment-related
Serious adverse events
All causality
Treatment-related
Severe adverse events
All causality
Treatment-related
Discontinuations due to adverse events
All causality
Treatment-related
Temporary discontinuations due to adverse events
All causality
Treatment-related

Placebo
N=318

Fesoterodine 4 mg
N=320

Fesoterodine 8 mg
N=313

215
112

320
203

397
304

130 (40.9)
81 (25.5)

192 (60.0)
150 (46.9)

222 (70.9)
192 (61.3)

5 (1.6)2 (0.6)3 (0.9)1 (0.3)00

4 (1.3)2 (0.6)6 (1.9)4 (1.3)3 (1.0)3 (1.0)11 (3.5)
8 (2.5)15 (4.7)
9 (2.8)14 (4.5)
13 (4.2)

1 (0.3)0

6 (1.9)2 (0.6)6 (1.9)2 (0.6)

Subjects were counted only once per treatment in each row, except for the number of adverse events.
One subject, who was not randomized but took the study drugs for the double-blind treatment period during the
run-in period due to being wrongly dispensed, was summarized in the actual treatment (placebo group).

All-causality adverse events that occurred in 2% of subjects in any treatment group aresummarized in Table S7.
Table S7 Adverse Events Reported by ≥2% of Subjects in Any Treatment Group[Number (%) of Subjects]
MedDRA System Organ Classes
Preferred Term (version 11.1)
Gastrointestinal disorders
Constipation
Diarrhoea
Dry mouth
Infections and infestations
Cystitis
Nasopharyngitis
Nervous system disorders
Dizziness
HeadacheRenal and urinary disorders
Dysuria
Residual urine

Placebo
N=318

Fesoterodine 4 mg
N=320

Fesoterodine 8 mg
N=313

15 (4.7)
3 (0.9)31 (9.7)

17 (5.3)
7 (2.2)93 (29.1)

33 (10.5)
3 (1.0)158 (50.5)

4 (1.3)21 (6.6)

12 (3.8)
19 (5.9)

7 (2.2)22 (7.0)

1 (0.3)5 (1.6)7 (2.2)10 (3.1)

2 (0.6)4 (1.3)0
5 (1.6)2 (0.6)7 (2.2)14 (4.5)
2 (0.6)

If the same subject in a given treatment had more than one occurrence in the same preferred term event category,
only the most severe occurrence was taken. Subjects were counted only once per treatment in each row.

Most of the all-causality adverse events were mild or moderate in severity. The percentage
of subjects with severe adverse events was low and similar among groups. The percentage ofsubjects who permanently discontinued the study due to adverse events was similar among
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the treatment groups. The adverse events leading to discontinuation are summarized in Table
S8.

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Table S8 Adverse Events Leading to Discontinuation [Number (%) of Subjects]
MedDRA System Organ Classes
Preferred Term (version 11.1)
Cardiac disorders
Palpitations
Eye disorders
Vision blurred
Visual acuity reduced
Gastrointestinal disorders
Abdominal discomfort
Abdominal pain
Diarrhoea
Dry mouth
NauseaVomiting
General disorders and administration site conditions
Chest pain
MalaisePain
Hepatobiliary disorders
Hepatic function abnormal
Infections and infestations
Cystitis
Tinea pedis
Urinary tract infection
Injury, poisoning and procedural complications
Pelvic fracture
Investigations
Alanine aminotransferase increased
Aspartate aminotransferase increased
Blood creatine phosphokinase increased
Electrocardiogram QT prolonged
Nervous system disorders
Autonomic nervous system imbalance
Cerebral infarction
Dizziness
HeadacheSomnolence
Psychiatric disorders
Depression
Renal and urinary disorders
Dysuria
Respiratory, thoracic and mediastinal disorders
AsthmaDyspnoea
Skin and subcutaneous tissue disorders
EczemaPlacebo
N=318

Fesoterodine 4 mg
N=320

Fesoterodine 8 mg
N=313

1 (0.3)00

2 (0.6)00
0

0
1 (0.3)1 (0.3)1 (0.3)1 (0.3)2 (0.6)000
0
2 (0.6)
1 (0.3)1 (0.3)1 (0.3)00
1 (0.3)7 (2.2)000
1 (0.3)0

1 (0.3)00

00
1 (0.3)00

1 (0.3)0
1 (0.3)0

1 (0.3)0
2 (0.6)00
0

0

1 (0.3)0

2 (0.6)
1 (0.3)00

00
1 (0.3)2 (0.6)

1 (0.3)000

1 (0.3)1 (0.3)0
1 (0.3)1 (0.3)00
2 (0.6)
1 (0.3)
0

0
0
0
0
0

0

2 (0.6)00

0

2 (0.6)0
1 (0.3)1 (0.3)
0

0
0

0

0

1 (0.3)The serious adverse events are summarized in Table S9.

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Table S9 Serious Adverse Events [Number (%) of Subjects]
MedDRA System Organ Classes
Preferred Term (version 11.1)

Placebo
N=318

Fesoterodine
4 mg
N=320

Fesoterodine
8 mg
N=313

1 (0.3)1 (0.3)1 (0.3)

0
0
0

0
0
0

1 (0.3)00

1 (0.3)1 (0.3)000
1 (0.3)

0
0
0

0
0

1 (0.3)1 (0.3)00

1 (0.3)00

1 (0.3)000

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Gastrointestinal disorders
Abdominal pain
Diarrhoea
Vomiting
General disorders and administration site conditions
Pyrexia
Infections and infestations
Abscess
Cellulitis
Urinary tract infection
Injury, poisoning and procedural complications
Pelvic fracture
Road traffic accident
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix carcinoma
Nervous system disorders
Cerebral infarction
Reproductive system and breast disorders
Pelvic pain

Only 1 serious adverse event (urinary tract infection) out of the 3 serious adverse events that
occurred in the fesoterodine treated subjects was considered to be treatment-related by theinvestigator. This event resolved. No deaths were reported in this study.
Overall, the frequency of laboratory test abnormalities was low and similar among thetreatment groups. The number of subjects who permanently discontinued the study due toadverse events associated with laboratory test abnormalities was small and similar among thetreatment groups (2 subjects in the placebo group, and 1 subject each in the fesoterodine 4
and 8 mg groups, respectively). There were no adverse events leading to temporary
discontinuations or serious adverse events, which were associated with laboratory test
abnormalities.
No clinically relevant changes or trends were apparent in the mean changes from baseline forsystolic blood pressure and diastolic blood pressure. A small increase from baseline in themean pulse rate and heart rate at Week 12 was observed in subjects receiving fesoterodine.
An increase in heart rate is a known effect of antimuscarinic drugs. ECG results did notsuggest evidence of an increased risk following treatment with fesoterodine. The mean
increases in residual urine volume were small and not clinically significant in each treatmentgroup (3.54 mL in the placebo group, and 8.62 mL and 10.47 mL in the fesoterodine 4 and
8 mg groups, respectively).
CONCLUSION(S): This was a 12-week, multicenter, randomized, double-blind, placebocontrolled, parallel-group, dose-finding study in subjects with OAB.
Both fesoterodine 4 mg/day and 8 mg/day demonstrated statistically significant decreases in
the mean number of UUI episodes (primary endpoint) and micturitions per 24 hours at Week
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PhRMA Web Synopsis
Protocol A0221005 – 13 August 2009 – Final

12 compared to placebo and dose dependent responses to fesoterodine 4 mg/day and8 mg/day were observed. Fesoterodine 4 mg/day and 8 mg/day were also found to be more
effective in most of the secondary endpoints compared to placebo.
Fesoterodine 4 mg/day and 8 mg/day had a favorable safety profile and were generally welltolerated compared to placebo in this study. The percentage of subjects who permanently
discontinued study due to adverse events was similar among the treatment groups and wasless than 5%. Most of the adverse events were mild or moderate in severity. The mostfrequently reported adverse events included known adverse events for antimuscarinic drugs
including dry mouth and constipation. These adverse events were more common in subjects
treated with fesoterodine than placebo and were more frequently reported in the fesoterodine
8 mg group than the 4 mg group.

090177e180d31d3c\0.11\Draft\Versioned On:02-Sep-2009 00:14

Overall, both fesoterodine 4 mg/day and 8 mg/day demonstrated a greater treatment effectthan placebo. Both fesoterodine doses were generally well tolerated compared to placebo inthis study. The safety and efficacy results in this study support the conclusion thatfesoterodine 4 mg/day and fesoterodine 8 mg/day could be recommended for OAB patients.

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