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Fesoterodine – A New Treatment Option for Overactive Bladder
average baseline values for the number of micturitions per 24-hour period
Table 5: Efficacy Results from Trial SP583
were similar across groups, and fesoterodine treatment produced
statistically significant reductions in this parameter compared with placebo
Placebo Tolterodine Fesoterodine
(p<0.001) (see Table 4). Additional analysis did not reveal significant
Change from baseline to study end ER 4mg 4mg 8mg
differences between the two active treatments. Furthermore, both doses of
Primary end-points
Micturitions/24 hours (n=279) (n=283) (n=265) (n=276)
fesoterodine produced statistically significant reductions from baseline in the
Baseline mean 12.0 11.5 11.6 11.9
number of UUI episodes per 24-hour period compared with placebo
Median % change -11.1 -13.8 -16.7 -18.6
(p<0.001). Again, average baseline values were similar across groups (see
UUI episodes/24 hours (n=211) (n=223) (n=199) (n=223)
Table 4). The median percentage change in number of UUI episodes per Baseline mean 3.7 3.8 3.8 3.7
24-hour period from baseline to end of treatment was -67% with 4mg
Median % change -50.0 -70.0 -80.0 -87.5
fesoterodine, -82% with 8mg fesoterodine and -40% in the placebo group
% positive treatment responses (n=279) (n=283) (n=265) (n=276)
(see Figure 1a). Significantly more subjects receiving either dose of
53 72 75 79
Secondary end-points
fesoterodine reported treatment response than those taking placebo
MVV/micturition (n=278) (n=282) (n=265) (n=275)
(p<0.001 for both doses versus placebo) (see Table 4). In terms of secondary
Baseline mean (ml) 150.2 154.3 160.0 153.9
end-points, the 8mg dose of fesoterodine yielded statistically significant
LS mean change (ml) 9.4 23.6 27.7 33.6
increases in MVV per micturition compared with placebo (p<0.001), with a Urgency episodes/24 hours (n=279) (n=283) (n=265) (n=276)
four-fold (33.6ml) greater mean increase from baseline to end of treatment Baseline mean 11.4 11.0 11.0 11.5
compared with those in the placebo group (8.38ml)
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(see Table 4). In
Median % change -11.1 -16.0 -17.6 -19.1
addition, both doses of fesoterodine significantly improved the mean
Continent days/24 hours (n=211) (n=223) (n=199) (n=223)
Baseline mean 0.8 0.6 0.8 0.6
number of continent days per week (p<0.001 for both doses) (see Table 4).
LS mean change 2.1 2.5 2.8 3.3
The total number of urgency episodes per 24-hour period was also
LS = least square; MVV = mean voided volume; UUI = urgency urinary incontinence.
significantly reduced compared with placebo (p<0.001 for both doses of
Adapted from Chapple et al. 2007.
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fesoterodine) (see Figure 1b).
Figure 2: Reduction in Severe Urgency and Urgency Urinary
Incontinence Episodes with Fesoterodine 8mg
Efficacy Results from SP583
The second phase III study had an almost identical design to study SP584.
Placebo Tolterodine 4mg Fesoterodine 8mg
However, this trial included an extra treatment arm, tolterodine ER 4mg,
0
which served as an active control. Initially, 1,409 patients were screened and
enrolled in a two-week single-blind placebo run-in period. Of the 1,409
-10
patients enrolled, 1,135 met the randomisation criteria at the end of the
-20
run-in period and were randomised to 12 weeks of once-daily treatment
-30
with two tablets of placebo, one placebo tablet plus fesoterodine 4mg, one
-40
-33.3%
placebo tablet plus fesoterodine 8mg or one placebo tablet plus tolterodine
ER 4mg; a so-called double-dummy design was used to ensure blinding.
c
hange from baseline in severe
-50
-45.0%*
c
y and UUI episodes per 24 hours
As with SP584, treatment with either dose of fesoterodine produced -60
-54.5%*
Median %
urgen
-70
As with SP584, treatment with either
*p<0.005 versus placebo; † p<0.05 versus tolterodine 4mg. Average baseline values 5.7–6.0.
UUI = urgency urinary incontinence.
dose of fesoterodine produced Adapted from Chapple et al., 2008.
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statistically significant reductions from
In terms of secondary end-points, treatment with either dose of
baseline in the primary end-points
fesoterodine resulted in significant increases in MVV per micturition
compared with placebo.
(p<0.001 versus placebo). Tolterodine was also significantly better than
placebo, confirming the validity of the study design (see Table 5).
Fesoterodine 4 or 8mg significantly improved the mean number of
statistically significant reductions from baseline in the primary continent days per week compared with placebo (p=0.007 and p<0.001,
end-points compared with placebo (see Table 5). Both doses respectively). However, the tolterodine ER group did not differ significantly
of fesoterodine and tolterodine significantly reduced the number of from placebo treatment. Fesoterodine 4mg (p=0.003), fesoterodine 8mg
micturitions per 24-hour period compared with placebo (p<0.001 for (p<0.001) and tolterodine (p<0.001) produced statistically significant
both doses and for tolterodine). Treatment with either dose of improvement in the total number of urgency episodes (grades 2–4 on the
fesoterodine or tolterodine produced statistically significant reductions Urinary Urgency Scale) per 24 hours versus placebo.
from baseline in the number of UUI episodes per 24-hour period
compared with placebo (p≤0.001). Furthermore, by end of treatment Additional analysis was conducted to determine whether there were
(last observation carried forward [LOCF]), 75% patients on fesoterodine statistically significant differences in efficacy between fesoterodine 8mg
4mg, 79% patients receiving fesoterodine 8mg and 72% of patients on and tolterodine.
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A post hoc inferential analysis on the primary and
tolterodine reported treatment benefit compared with 53% of patients secondary end-points of SP583 was undertaken to test this hypothesis. In
receiving placebo (p<0.001 for all active groups). addition, pooled analyses of data from the two phase III trials were
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