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Overactive Bladder
Table 6: Efficacy of Fesoterodine 4mg versus Fesoterodine 8mg Table 7: Patient-reported Outcomes Assessed Using the
at 12 Weeks King’s Health Questionnaire
Fesoterodine
Fesoterodine
Baseline Mean Placebo 4mg 8mg
Improvement versus baseline (absolute value) Placebo 4mg 8mg
(Median % Change)
Severity/coping behaviour 7.4 11.3* 13.7*
†
Micturitions/24 hours 12.0–12.2 -10.0 -15.5* 17.1*
Emotions 9.1 12.4* 15.3*
†
(n=545) (n=532) (n=543)
Role limitations 12.5 18.5* 21.4*
UUI episodes/24 hours 3.7–3.9 -42.9 -75.0* -83.3*
†
Physical limitations 11.4 17.2* 19.6*
(n=416) (n=427) (n=441)
Social limitations 7.9 11.6* 13.8*
% positive treatment 49 69* 77*
†
Sleep/energy 7.8 10.7* 12.3*
responses (n=545) (n=532) (n=543)
Personal relationship 5.9 7.8 9.6*
MVV/micturition 155–156 9.0 22.2* 33.6*
†
Incontinence impact 14.2 19.6* 22.5*
(n=543) (n=531) (n=542)
General health perception 2.4 2.9 2.6
Continent days/ 0.7–0.8 1.8 2.6* 3.1*
†
*p<0.01 versus placebo; † p<0.05 versus fesoterodine 4mg.
24 hours (n=416) (n=427) (n=441) Adapted from Kelleher et al., 2008.
20
*p<0.01 versus placebo; † p<0.05 versus fesoterodine 4mg.
MVV = mean voided volume; UUI = urgency urinary incontinence.
Table 8: Treatment-related Adverse Events Occurring in 2% of
Adapted from Khullar et al., 2008.
19
Patients and More Frequently than with Placebo
Figure 3: Fesoterodine Dose–Response Relationship in Adverse Events Placebo Tolterodine ER 4mg Fesoterodine 8mg
Reduction of Urgency Urinary Incontinence Episodes
(n=283) (n=290) (n = 287)
%% %
Dry mouth 7.1 16.9 33.8
Placebo
4 Fesoterodine 4mg
Constipation 1.4 2.8 4.5
Fesoterodine 8mg
Dry eye 0 <1 4.2
Fatigue <1 0 2.1
Nausea <1 2.1 1.4
3
Increased alanine <1 0 2.1
*
aminotransferase
*
2
*
Dry throat 0 1 2.8
*
Nasopharyngitis 2.5 3.4 1.7
Adapted from Chapple et al., 2008.
18
Number of UUI episodes per 24 hours
*
*
1
BL 2 weeks 8 weeks 12 weeks 8mg compared with tolterodine ER 4mg (p<0.05) (see Table 5).
EOT
Fesoterodine 8mg also augmented the response rate significantly
*p<0.001 versus placebo and two weeks and at end of treatment (EOT). † p<0.05 versus
compared with tolterodine ER 4mg (p<0.05), and significantly
fesoterodine 4mg.
BL = baseline; UUI = urgency urinary incontinence.
increased MVV/micturition compared with tolterodine ER 4mg
Adapted from Khullar et al., 2008.
19
(p<0.05). Finally, fesoterodine 8mg was significantly more efficacious
than tolterodine in elevating the number of continent days (p<0.05)
undertaken to determine whether there were statistically significant (see Table 5). Collectively, these findings clearly showed that the
differences in efficacy between the two doses (4 and 8mg) of
fesoterodine
19
and to evaluate the effects and possible differences
between the two doses of fesoterodine on HRQoL.
20
Notably, the fesoterodine 8mg dose
In SP583, patients with OAB in both the active treatment and active
performed significantly better than
control groups showed significant improvements in most bladder diary
fesoterodine 4mg in improving all
variables compared with placebo. Fesoterodine 8mg was statistically
diary variables (p<0.05), except the
better than tolterodine ER 4mg in improving diary variables such as
UUI episodes per 24 hours, UUI episodes per 24 hours, treatment frequency of micturitions.
response, MVV/micturition, continent days per week and severe
urgency with UUI (p<0.05 for all parameters).
18
Figure 2 shows the
median percentage change from baseline in severe urgency and UUI maximum recommended dose of fesoterodine (8mg) was significantly
episodes per 24 hours obtained with placebo, tolterodine ER 4mg and more effective than the recommended dose of tolterodine ER (4mg) in
fesoterodine 8mg. In the fesoterodine 8mg group, the median improving a number of OAB outcomes.
percentage change in number of severe urgency and UUI episodes per
24-hour period from baseline to end of treatment was significantly The pooled analysis that compared the efficacy of fesoterodine 4 and
greater than that seen with either tolterodine ER 4mg or placebo 8mg also yielded interesting results, which were recently published by
(p<0.05 for both) (see Figure 2). Khullar et al.
19
Both doses of fesoterodine achieved rapid and sustained
treatment response rates at two weeks, and this response was sustained
In addition, the median percentage change from baseline in UUI throughout the study. Notably, the fesoterodine 8mg dose performed
episodes per 24 hours was significantly reduced with fesoterodine significantly better than fesoterodine 4mg in improving all diary
66 EUROPEAN UROLOGICAL REVIEW