PhRMA Web Synopsis
Protocol A0221006 – 4 June 2010 – 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 United States
Package Insert (USPI)NATIONAL CLINICAL TRIAL NO.: NCT00658684
PROTOCOL NO.: A0221006
PROTOCOL TITLE: An Open-Label, Multicenter, Long Term Study to Evaluate The
Safety, Tolerability and Efficacy of Fesoterodine in Patients With Overactive Bladder090177e18140339c\Approved\Approved On: 11-Jun-2010 15:39

Study Center(s): 12 centers in Japan
Study Initiation Date and Completion Dates: 01 February 2008 to 06 August 2009
Phase of Development: Phase 3
Study Objective(s):The primary objective of the study was to assess the long term safety and tolerability offesoterodine in patients with overactive bladder (OAB).
The secondary objective of the study was to assess the long term efficacy of fesoterodine inpatients with OAB.
METHODS
Study Design: This was an open-label, multicenter, long term study in Japanese patientswith OAB. Subjects were to be treated with fesoterodine for up to 52 weeks requiring a totalof 15 clinic visits during the study. The study design is presented in Figure S1.
Subjects were screened at Visit 1 (Screening/enrollment visit). Eligible subjects then entereda run-in phase during which they completed a 3-day micturition diary for 3 consecutive daysin 7 days prior to Visit 2 (Baseline visit). At Visit 2, the diary data and screening laboratory
data were checked against the entry criteria, and the eligible subjects received fesoterodine
4 mg/day for 4 weeks. At Visit 3, the investigator confirmed the efficacy of fesoterodine
4 mg by the diary data and interview. It was possible to increase the dose to 8 mg, if theinvestigator judged that the efficacy of 4 mg was insufficient and that there were nosafety/tolerability issues for the subject. This increase only occurred when requested by the
subject. The dose was allowed to be reduced from 8 mg to 4 mg at Visit 4, provided that theinvestigator judged that the continued treatment with 4 mg would be useful to the patient andPage 1PhRMA Web Synopsis
Protocol A0221006 – 4 June 2010 – Finalthat the continued treatment with 8 mg might result in tolerability issues and that the patient
requested continued treatment with fesoterodine 4 mg. Thereafter, all subjects remained on
the dose selected at Visit 4 until the end of the trial unless a safety/tolerability problem
occurred. If safety/tolerability problem occurred and the subject could not continue
treatment with 8 mg, the investigator could consider the discontinuing the patient’s
participation in the study.
Figure S1 Study Design
Day -21 to
Day -7Visit
1090177e18140339c\Approved\Approved On: 11-Jun-2010 15:39

Run-in peiord

Day 0

Day 28±3 daysDay 42±3 daysDay 56±3 days

VIsit
2

Visit
3

Phone
contact

Visit
4

Fesoterodine 4 mg

Visit 4 + every
28 days±7daysDay 364±7days/ET

Visits5 to 14

Visit

Fesoterodine 8 mg

Fesoterodine 8 mg

Fesoterodine 4 mg

Fesoterodine 4 mg

15

Visit 1: Screening/enrollment visit
Visit 2: Baseline visit
Visit 3: Week 4Visits 4 to 14: Every 4 weeks after Visit 3
Visit 15: End-of-trial visit (Week 52 or early termination [ET])Number of Subjects (Planned and Analyzed): A total of 150 subjects were planned and
153 subjects were assigned to treatment. As study drug administration could not be verified
for 1 subject, 152 subjects were analyzed for safety, and 150 subjects were analyzed for
efficacy.
Diagnosis and Main Criteria for Inclusion: Male or female outpatients 20 years or older
who exhibit signs or symptoms of OAB with urinary urgency and increased urinary
frequency (a known medical history  6 months prior to Visit 1). OAB patients with orwithout urgency urinary incontinence who exhibit, during the 3-day micturition diary periodprior to Visit 2 (Baseline visit), a total of at least 3 urinary urgency episodes and at least 8
micturitions per 24 hours, document the voided volume of each micturition during any 1 day
and the first micturition of the following day, and indicate at least moderate problems(moderate, severe or many severe problems) based on Patient Perception of Bladder
Condition (PPBC) at Visit 2. Patients who have a known neurological disease influencing
bladder function, a complication of lower urinary tract pathology potentially responsible forurgency or incontinence, clinically relevant lower urinary tract obstruction or pelvic organ
prolapse, or predominant symptoms of stress urinary incontinence based on the assessment of
the investigator were excluded.

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Protocol A0221006 – 4 June 2010 – Final

Study Treatment: This was an open-label study. Subjects took one fesoterodine 4-mg or 8mg tablet with water every morning with or without food. All enrolled subjects were treatedwith fesoterodine 4 mg for the first 4 weeks and were permitted a one-time dose increase to
8 mg at Visit 3 (at Week 4). The dose was allowed to be reduced from 8 mg to 4 mg at Visit
4 (at Week 8), and thereafter, all subjects remained on the dose selected at Visit 4 until theend of the trial. The decision to maintain, increase or decrease the dose was based on a
discussion between the subject and the investigator regarding drug efficacy and tolerability.
Efficacy Evaluations: A micturition diary was completed by subjects to evaluate changes
from baseline in mean number of urgency urinary incontinence (UUI) episodes per 24 hours,mean number of micturitions per 24 hours, mean number of incontinence episodes per 24hours, mean number of urgency episodes per 24 hours, mean number of nighttime
micturitions per 24 hours and mean voided volume per micturition at Weeks 4, 8, 28 and 52.
Subjects were also required to complete King’s Health Questionnaire (KHQ), Overactive
Bladder Questionnaire (OAB-q) and Patient Perception of Bladder Condition (PPBC) at
Weeks 28 and 52.

090177e18140339c\Approved\Approved On: 11-Jun-2010 15:39

Safety Evaluations: Adverse events, clinical laboratory test (hematological test, chemistry
test, urine test), vital signs (blood pressure, pulse rate), weight, 12-lead electrocardiogram(ECG) and residual urine volume (sonographic).
Statistical Methods:
Efficacy: The efficacy analysis set included all subjects who took at least one dose of study
drug and contribute data to baseline and at least one valid post-baseline efficacy assessment.
For micturition diary endpoints, actual value and change from baseline at each visit weresummarized with descriptive statistics (number of subjects, mean, standard deviation,
minimum, median, maximum and the 95% confidence interval for the mean). For KHQ,
OAB-p and PPBC, actual values and changes from baseline at each visit were summarizedusing descriptive statistics. Shift tables were also prepared for PPBC response from baseline
to Week 28 and 52.
Subgroup analyses by treatment dose history (fesoterodine 4 mg for the entire treatment
period; increased to fesoterodine 8 mg at Week 4 and reduced to 4 mg at Week 8; increased
to fesoterodine 8 mg at Week 4 and remained at 8 mg) were performed for the above efficacy
analyses.
Safety: The safety analysis set included all subjects who took at least one dose of study drug.
Standard tables were produced for adverse events, vital signs, ECG data and clinicallaboratory data in accordance with Pfizer Data Standards (PDS). For residual urinary volume(mL), actual sonographic values and change from the baseline values at each visit weresummarized using descriptive statistics. Subgroup analyses by treatment dose history for theabove analyses were performed.

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Protocol A0221006 – 4 June 2010 – Final

RESULTS
Subject Disposition and Demography: The disposition of subjects is summarized inTable S1. Of 152 treated subjects, 99 (65.1%) remained on a dose of fesoterodine 4 mg
throughout the study period (subjects who remained on a dose of 4 mg), and 53 (34.9%)
increased the dose to 8 mg at Week 4. Of 53 subjects whose dose was increased to 8 mg, thedose of 25 subjects (16.4% of 152 subjects) was reduced to 4 mg at Week 8 (subjects whose
dose was increased to 8 mg and then reduced to 4 mg) and 28 (18.4% of 152 subjects)
remained on a dose of 8 mg after Week 4 (increased to 8 mg and maintained).
Of 152 subjects, 19 subjects (12.5%) discontinued treatment. The most commonly reported
reasons for discontinuations were adverse events (10 subjects, 6.6%) and consent withdrawal(6 subjects, 3.9%).
Table S1

Subject Disposition From the Start of the Trial to Week 52 [Number (%) of
Subjects]

090177e18140339c\Approved\Approved On: 11-Jun-2010 15:39

Total
a)

4 mg

Treatment dose history
4 mg> 8 mg> 4 mg

4 mg > 8 mg

99
97

25
25

28
28

Number of treated subjects
Efficacy analysis set

152
150b)

Safety analysis set
Discontinuations
Adverse events
Not related to treatment
Related to treatment
Consent withdrawal
Lack of efficacy
Othersc)152
19 (12.5)

99
15 (15.2)

25
3 (12.0)28

3 (2.0)7 (4.6)6 (3.9)1 (0.7)2 (1.3)2 (2.0)6 (6.1)4 (4.0)1 (1.0)2 (2.0)1 (4.0)1 (4.0)1 (4.0)0000
1 (3.6)0

1 (3.6)0a) Excluding 1 subject whose study drug administration could not be verifiedb) Excluding 2 subjects without any valid post-baseline micturition dairy assessmentc) Inclusion criteria not met (1 subject) and pregnancy (1 subject)
4 mg: Remained on a dose of fesoterodine 4 mg for the entire treatment period (subjects who remained on a dose of 4 mg)
4 mg > 8 mg > 4 mg: Increased to fesoterodine 8 mg at Week 4 and reduced to 4 mg at Week 8 (subjects whose dose wasincreased to 8 mg and then reduced to 4 mg)
4 mg > 8 mg: Increased to fesoterodine 8 mg at Week 4 and remained on a dose of 8 mg after Week 4 (subjects whose dose
was increased to 8 mg and maintained)

The mean age of the total of 152 subjects was 52.7 years, and approximately 20% of thesubjects were 65 years or older. Nineteen subjects (12.5%) were male, and 133 subjects(87.5%) were female. The mean weight was 56.3 kg, the mean BMI was 22.8 kg/m2, and themean height was 157.3 cm. The mean OAB duration (range) was 6.2 years (0.6 to 35.2
years), and 47 subjects (30.9%) received drug treatment for OAB within 4 weeks before thestart of the study.
Efficacy Results: The results of micturition diary endpoints are summarized in Table S2. In
all subjects, for all of the micturition diary endpoints (mean number of UUI episodes per 24hours, mean number of micturitions per 24 hours, mean number of incontinence episodes per

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PhRMA Web Synopsis
Protocol A0221006 – 4 June 2010 – Final

24 hours, mean number of urgency episodes per 24 hours, mean number of nighttime
micturitions per 24 hours and mean voided volume per micturition), most of the
improvement occurred by Week 8 and the level of improvement was maintained up to Week
52.

090177e18140339c\Approved\Approved On: 11-Jun-2010 15:39

For all of the diary endpoints by treatment dose history, the subjects who increased the doseto 8 mg at Week 4 (including those whose dose was reduced to 4 mg at Week 8) had more
severe symptoms of OAB at baseline than those who remained on a dose of 4 mg (subjects
who remained on a dose of 4 mg). The subjects who remained on a dose of 4 mg showedmarked improvement in all diary endpoints by Week 8, and the level of improvement wasmaintained up to Week 52. The subjects who increased the dose to 8 mg at Week 4 due toinsufficient efficacy showed marked improvement after a dose increase. Of these subjects,
those subjects whose dose was reduced to 4 mg mainly due to tolerability problems at Week
8 (increased to 8 mg and reduced to 4 mg) maintained the level of improvement even after
dose reduction. In subjects who continued a dose of 8 mg after Week 8 (increased to 8 mg
and maintained), a trend toward improvement over time was shown following dose increase
and the level of improvement was greater than that seen with subjects who remained on adose of 4 mg or whose dose was reduced to 4 mg.

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Protocol A0221006 – 4 June 2010 – Final

Table S2

Changes From Baseline in Micturition Diary Endpoints: Total and by
Treatment Dose History

090177e18140339c\Approved\Approved On: 11-Jun-2010 15:39

Efficacy endpointsa)
Mean UUI episodes b)
Baseline
At Week 4
At Week 8
At Week 28
At Week 52
At Week 52 (LOCF)
Mean number of
micturition
Baseline
At Week 4
At Week 8
At Week 28
At Week 52
At Week 52 (LOCF)
Mean incontinence
episodesc)
Baseline
At Week 4
At Week 8
At Week 28
At Week 52
At Week 52 (LOCF)
Mean number ofurgency episodes
Baseline
At Week 4
At Week 8
At Week 28
At Week 52
At Week 52 (LOCF)
Mean number ofnighttime micturitionsd)
Baseline
At Week 4
At Week 8
At Week 28
At Week 52
At Week 52 (LOCF)

n
101
101
100
95
92
101

Total
(N=150)MeanSD
1.61.48-0.861.104-1.151.293-1.281.282-1.341.553-1.351.521

4 mg (N=97)n
MeanSD60
1.41.23
60-0.991.117
59-1.161.173
56-1.241.185
54-1.231.228
60-1.191.176

Treatment dose history
4mg > 8mg > 4mg (N=25)nMeanSD17
1.71.24
17-0.731.281
17-1.311.450
16-1.251.518
15-1.181.661
17-1.221.568

4 mg > 8 mg (N=28)nMeanSD24
2.12.04
24-0.630.918
24-1.001.491
23-1.411.385
23-1.712.097
24-1.822.120

150
150
148
137
133
150

11.32.85-1.421.855-2.111.946-2.332.338-2.632.220-2.492.172

97
97
95
87
84
97

11.02.69-1.731.899-2.031.897-2.182.351-2.482.020-2.351.970

25
25
25
23
22
25

11.22.71-1.281.403-1.812.035-2.062.260-2.212.196-2.042.135

28
28
28
27
27
28

12.33.31-0.451.757-2.632.005-3.022.315-3.442.683-3.362.673

103
103
102
97
94
103

1.81.74-0.841.140-1.231.354-1.391.476-1.371.589-1.381.557

62
62
61
58
56
62

1.61.34-0.991.166-1.161.272-1.261.322-1.261.331-1.241.282

17
17
17
16
15
17

1.81.33-0.801.225-1.431.504-1.311.542-1.161.847-1.201.740

24
24
24
23
23
24

2.52.63-0.490.963-1.281.486-1.771.779-1.751.962-1.861.990

150
150
148
137
133
150

4.53.40-1.692.009-2.442.194-2.542.597-2.762.901-2.612.885

97
97
95
87
84
97

3.93.31-1.771.856-2.321.881-2.411.855-2.552.579-2.302.531

25
25
25
23
22
25

6.23.72-1.752.572-2.592.940-3.123.304-2.803.193-2.933.319

28
28
28
27
27
28

5.12.87-1.372.001-2.702.463-2.463.780-3.373.565-3.403.504

116
116
115
106
103
116

1.41.04-0.310.727-0.430.797-0.470.752-0.570.807-0.500.826

69
69
68
62
60
69

1.21.04-0.340.752-0.330.812-0.360.788-0.460.904-0.380.908

23
23
23
21
20
23

1.60.93-0.450.556-0.550.845-0.560.694-0.680.546-0.620.614

24
24
24
23
23
24

1.61.05-0.080.776-0.600.688-0.710.661-0.750.698-0.710.718

N, Efficacy analysis set; n, Number of subjects evaluated; SD, standard deviation; hrs, hoursa) Number of times per 24 hours is shown.
b) Of the efficacy analysis set, the subjects whose mean number of UUI episodes per 24 hours at baseline was greater than 0(OAB Wet subjects) were analyzed.
c) Of the efficacy analysis set, the subjects whose mean number of incontinence episodes per 24 hours at baseline wasgreater than 0 were analyzed.
d) Of the efficacy analysis set, the subjects whose mean number of nighttime micturitions per 24 hours at baseline wasgreater than 0 were analyzed.
4 mg: Remained on a dose of fesoterodine 4 mg for the entire treatment period (subjects who remained on a dose of 4 mg)
4 mg > 8 mg > 4 mg: Increased to fesoterodine 8 mg at Week 4 and reduced to 4 mg at Week 8 (subjects whose dose wasincreased to 8 mg and then reduced to 4 mg)
4 mg > 8 mg: Increased to fesoterodine 8 mg at Week 4 and remained on a dose of 8 mg after Week 4 (subjects whose dose
was increased to 8 mg and maintained)

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Protocol A0221006 – 4 June 2010 – Final

Table S2

Changes From Baseline in Micturition Diary Endpoints: Total and by
Treatment Dose History (continued)

Efficacy endpoints

Total(N=150)MeanSD

Treatment dose history
4mg > 8mg > 4mg (N=25)nMeanSD

4 mg > 8 mg (N=28)
Mean voided volume nnMeanSDper micturition (mL)
Baseline
150 158.148.09
97
25
28
162.848.78
156.142.75
143.648.73
At Week 4
150 16.6741.908
97
25
28
20.5844.357
12.1843.399
7.1629.231
At Week 8
148 22.3451.339
95
25
28
21.8658.194
23.0035.061
23.3738.273
At Week 28
137 32.5946.389
87
23
27
31.9850.365
40.2041.613
28.1036.431
At Week 52
133 35.9244.007
84
22
27
40.2147.646
33.0240.772
24.9532.414
At Week 52 (LOCF)
150 33.4245.175
97
25
28
37.0849.276
28.2240.693
25.3831.890
N, Efficacy analysis set; n, Number of subjects evaluated; SD, standard deviation; hrs, hours
4 mg: Remained on a dose of fesoterodine 4 mg for the entire treatment period (subjects who remained on a dose of 4 mg)
4 mg > 8 mg > 4 mg: Increased to fesoterodine 8 mg at Week 4 and reduced to 4 mg at Week 8 (subjects whose dose wasincreased to 8 mg and then reduced to 4 mg)
4 mg > 8 mg: Increased to fesoterodine 8 mg at Week 4 and remained on a dose of 8 mg after Week 4 (subjects whose dose
was increased to 8 mg and maintained)

090177e18140339c\Approved\Approved On: 11-Jun-2010 15:39

4 mg (N=97)n
MeanSD

The changes in KHQ, OAB-q and PPBC scores showed improvement in quality of life
(QOL) from baseline at Week 52. The KHQ and OAB-q scores improved particularly inthose who increased the dose to 8 mg and maintained the dose, whose QOL was more
severely impaired at baseline than those who remained on a dose of 4 mg or whose dose was
reduced to 4 mg.
Safety Results: Adverse events reported during the study period are summarized inTable S3. Of 152 subjects, 138 (90.8%) experienced 434 all causality adverse events, and
102 (67.1%) experienced 170 treatment-related adverse events. By treatment dose history,
the incidence of all causality adverse events was 91.9% in 4 mg-treated subjects (91/99) and
88.7% in subjects who increased the dose to 8 mg at Week 4 (47/53; including those whose
dose was reduced to 4 mg at Week 8). The incidence of all causality adverse events with orwithout dose increase was similar. The incidence of treatment-related adverse events was
61.6% in 4 mg-treated subjects (61/99) and 77.4% in subjects who increased the dose to 8 mg
at Week 4 (41/53; including those whose dose was reduced to 4 mg at Week 8). The
incidence of treatment-related adverse events was slightly higher for those who increased thedose to 8 mg at Week 4.

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Protocol A0221006 – 4 June 2010 – Final

Table S3

Overall Summary of Treatment-Emergent Adverse Events: Total and by
Treatment Dose History [Number (%) of Subjects]

152

4 mg
99

Treatment dose history
4 mg > 8 mg > 4 mg
25

4 mg > 8 mg
28

138 (90.8)
102 (67.1)

91 (91.9)
61 (61.6)

25 (100)
25 (100)

22 (78.6)
16 (57.1)

434
170
1 (0.7)0269
94
1 (1.0)
0

92
48
0
0

73
28
0
0

10 (6.6)
7 (4.6)8 (8.1)6 (6.1)2 (8.0)1 (4.0)0030 (19.7)
23 (15.1)

6 (6.1)023 (92.0)
23 (92.0)

1 (3.6)0

Total090177e18140339c\Approved\Approved On: 11-Jun-2010 15:39

Subjects evaluable for safety
Number of subjects with adverse events
All causality
Treatment-related
Number of adverse events
All causality
Treatment-related
Subjects with serious adverse events
Subjects with severe adverse events
Number of subjects who discontinued treatment
due to adverse events
All causality
Treatment-related
Number of subjects with dose reduction or
temporary discontinuation due to adverse events
All causality
Treatment-related

4 mg: Remained on a dose of fesoterodine 4 mg for the entire treatment period (subjects who remained on a dose of 4 mg)
4 mg > 8 mg > 4 mg: Increased to fesoterodine 8 mg at Week 4 and reduced to 4 mg at Week 8 (subjects whose dose wasincreased to 8 mg and then reduced to 4 mg)
4 mg > 8 mg: Increased to fesoterodine 8 mg at Week 4 and remained on a dose of 8 mg after Week 4 (subjects whose dose
was increased to 8 mg and maintained)

All causality adverse events reported in 2% of subjects are summarized in Table S4. The
majority of adverse events observed were mild, and no severe adverse events were reported.

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Protocol A0221006 – 4 June 2010 – Final

Table S4. Adverse Events Reported by  2% of Subjects: Total and by Treatment
Dose History [Number (%) of Subjects]

090177e18140339c\Approved\Approved On: 11-Jun-2010 15:39

MedDRA System Organ Class
Preferred Term (ver. 11.1)

Total(N=152)4 mg(N=99)

Treatment dose history
4 mg > 8 mg > 4 mg
(N=25)

4 mg > 8 mg
(N=28)

Number of subjects with138 (90.8)
91 (91.9)25 (100)
22 (78.6)
adverse events
Number of adverse events
434
269
92
73
Ear and labyrinth disorders
Vertigo3 (2.0)2 (2.0)0
1 (3.6)Eye disorders
Vision blurred
3 (2.0)2 (2.0)1 (4.0)0
Gastrointestinal disorders
Abdominal pain upper
5 (3.3)3 (3.0)1 (4.0)1 (3.6)
Constipation
20 (13.2)
11 (11.1)
7 (28.0)
2 (7.1)
Diarrhoea
11 (7.2)
5 (5.1)
3 (12.0)
3 (10.7)
Dry mouth
77 (50.7)
43 (43.4)
21 (84.0)
13 (46.4)
Gastritis
9 (5.9)8 (8.1)1 (4.0)0
Nausea4 (2.6)
1 (1.0)2 (8.0)1 (3.6)
Periodontitis
3 (2.0)0
1 (4.0)2 (7.1)
Stomatitis
4 (2.6)3 (3.0)0
1 (3.6)
Infections and infestations
Cystitis
12 (7.9)8 (8.1)1 (4.0)3 (10.7)
Gastroenteritis
3 (2.0)3 (3.0)00Nasopharyngitis
50 (32.9)
35 (35.4)
7 (28.0)
8 (28.6)
Upper respiratory tract infection
12 (7.9)8 (8.1)2 (8.0)2 (7.1)
Injury, poisoning andprocedural complications
Contusion
3 (2.0)1 (1.0)2 (8.0)
0
Joint sprain
3 (2.0)3 (3.0)00Investigations
ALT increased
4 (2.6)3 (3.0)1 (4.0)0
AST increased
4 (2.6)3 (3.0)1 (4.0)0Musculoskeletal andconnective tissue disorders
Arthralgia
6 (3.9)5 (5.1)1 (4.0)0
Back pain
16 (10.5)
12 (12.1)
1 (4.0)3 (10.7)
Nervous system disorders
Dizziness
6 (3.9)3 (3.0)2 (8.0)1 (3.6)
Headache
5 (3.3)5 (5.1)00Somnolence
5 (3.3)
1 (1.0)2 (8.0)2 (7.1)
Psychiatric disorders
Insomnia
3 (2.0)2 (2.0)0
1 (3.6)
Renal and urinary disorders
Dysuria
6 (3.9)2 (2.0)3 (12.0)
1 (3.6)
Residual urine
3 (2.0)1 (1.0)2 (8.0)0Urine flow decreased
4 (2.6)
1 (1.0)2 (8.0)1 (3.6)
Respiratory, thoracic andmediastinal disorders
Rhinitis allergic
7 (4.6)4 (4.0)1 (4.0)2 (7.1)Skin and subcutaneous tissue
disordersEczema4 (2.6)3 (3.0)0
1 (3.6)
4 mg: Remained on a dose of fesoterodine 4 mg for the entire treatment period (subjects who remained on a dose of 4 mg)
4 mg > 8 mg > 4 mg: Increased to fesoterodine 8 mg at Week 4 and reduced to 4 mg at Week 8 (subjects whose dose wasincreased to 8 mg and then reduced to 4 mg)
4 mg > 8 mg: Increased to fesoterodine 8 mg at Week 4 and remained on a dose of 8 mg after Week 4 (subjects whose dose
was increased to 8 mg and maintained)
N: Safety analysis set, ALT: alanine aminotransferase, AST: aspartate aminotransferase

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Protocol A0221006 – 4 June 2010 – Final

The adverse events leading to discontinuation are summarized in Table S5. A total of 10
subjects (6.6%) discontinued treatment due to adverse events.
Table S5

Summary of Adverse Events Leading to Discontinuations [Number (%) of
Subjects]

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MedDRA System Organ Class
Preferred Term (ver. 11.1)

Total(N=152)Ear and labyrinth disorders
Tinnitus
1 (0.7)
Gastrointestinal disorders
Chapped lips
1(0.7)
Dry mouth2(1.3)
Gastritis1(0.7)
Nausea1(0.7)
Investigations
ALT increased
3(2.0)
AST increased
1(0.7)
Gamma-glutamyltransferase increased
1(0.7)
Urobilin urine present
1(0.7)
Musculoskeletal and connective tissue disorders
Intervertebral disc disorder1(0.7)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer1(0.7)
Renal and urinary disorders
Dysuria1(0.7)
N: Safety analysis set, ALT: alanine aminotransferase, AST: aspartate aminotransferase

One serious adverse event (Intervertebral disc disorder) was reported in 1 patient, but nocausality to the study drug was identified. No deaths were reported in this study.
Overall, there were no clinically significant findings observed in clinical laboratory tests,
blood pressure, pulse rate or 12 lead ECG, and no clinically significant changes wereobserved in residual urinary volume.
CONCLUSIONS:
Based on the results of the open-label, multicenter, long term study of fesoterodine 4 mg or 8
mg once daily in patients with OAB for 52 weeks, the following overall conclusions wereobtained;

The majority of adverse events reported was mild in severity and were those related toantimuscarinic action such as dry mouth.

The treatment with fesoterodine for 52 weeks in patients with OAB was safe and welltolerated.

Fesoterodine demonstrated sustained efficacy throughout 52 weeks of treatment inpatients with OAB.

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Protocol A0221006 – 4 June 2010 – Final

OAB symptoms were improved by increasing the dose to 8 mg in subjects who had
insufficient efficacy at a dose of 4 mg.



The subjects who experienced tolerability problems after a dose increase to 8 mg wereable to continue treatment by reducing the dose back to 4 mg, thereby maintaining thelevel of improvement in OAB symptoms.

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