The safety of TOVIAZ was evaluated in Phase 2 and 3 controlled trials in a total
of 2859 patients with overactive bladder of which 2288 were treated with fesoterodine.
Of this total, 782 received TOVIAZ 4 mg/day, and 785 received TOVIAZ 8 mg/day in
Phase 2 or 3 studies with treatment periods of 8 or 12 weeks. Approximately 80%
of these patients had >10 weeks exposure to TOVIAZ in these trials.
A total of 1964 patients participated in two 12-week, Phase 3 efficacy and safety
studies and subsequent open-label extension studies. In these 2 studies combined,
554 patients received TOVIAZ 4 mg/day and 566 patients received TOVIAZ 8 mg/day.
In Phase 2 and 3 placebo-controlled trials combined, the incidences of serious adverse
events in patients receiving placebo, TOVIAZ 4 mg, and TOVIAZ 8 mg were 1.9%, 3.5%,
and 2.9%, respectively. All serious adverse events were judged to be not related
or unlikely to be related to study medication by the investigator, except for four
patients receiving TOVIAZ who reported one serious adverse event each: angina, chest
pain, gastroenteritis, and QT prolongation on ECG.
The most commonly reported adverse event in patients treated with TOVIAZ was dry
mouth. The incidence of dry mouth was higher in those taking 8 mg/day (35%) and
in those taking 4 mg/day (19%), as compared to placebo (7%). Dry mouth led to discontinuation
in 0.4%, 0.4%, and 0.8% of patients receiving placebo, TOVIAZ 4 mg, and TOVIAZ 8
mg, respectively. For those patients who reported dry mouth, most had their first
occurrence of the event within the first month of treatment.
The second most commonly reported adverse event was constipation. The incidence
of constipation was 2% in those taking placebo, 4% in those taking 4 mg/day, and
6% in those taking 8 mg.
Table 3 lists adverse events, regardless of causality, that were reported in the
combined Phase 3, randomized, placebo-controlled trials at an incidence greater
than placebo and in 1% or more of patients treated with TOVIAZ 4 or 8 mg once daily
for up to 12 weeks.
Table 3 Adverse events with an incidence exceeding the placebo rate and reported
by ≥1% of patients from double-blind, placebo-controlled Phase 3 trials of 12 weeks
treatment duration
Patients also received TOVIAZ for up to three years in open-label extension phases
of one Phase 2 and two Phase 3 controlled trials. In all open label trials combined,
857, 701, 529, and 105 patients received TOVIAZ for at least 6 months, 1 year, 2
years, and 3 years respectively. The adverse events observed during long-term, open-label
studies were similar to those observed in the 12-week, placebo-controlled studies,
and included dry mouth, constipation, dry eyes, dyspepsia and abdominal pain. Similar
to the controlled studies, most adverse events of dry mouth and constipation were
mild to moderate in intensity. Serious adverse events, judged to be at least possibly
related to study medication by the investigator, and reported more than once during
the open-label treatment period of up to 3 years included urinary retention (3 cases),
diverticulitis (3 cases), constipation (2 cases), irritable bowel syndrome (2 cases),
and electrocardiogram QT corrected interval prolongation (2 cases).