Background: A once-daily (QD), extended-release formulation of trospium chloride has been developed for the treatment of overactive bladder syndrome (OAB). The effect of treatment on the core OAB symptoms of urgency, frequency, and urgency urinary incontinence (UUI) can be assessed using the OAB-symptom composite score (OAB-SCS) which reflects subjects’ experience of OAB as a whole rather than as a collection of individual symptoms. Analyses are presented of pooled OAB-SCS data from two Phase III studies of trospium 60 mg QD in subjects with OAB.
Methods: Subjects aged ≥18 years with OAB of ≥6 months’ duration were eligible for enrollment in these multicenter, parallel-group, double-blind, placebo-controlled trials. Three-day bladder diary data were used to identify subjects with urinary urgency, frequency, and an average of ≥1 UUI episode per day, who were then randomized (1:1) to receive trospium 60 mg QD or placebo for 12 weeks. The OAB-SCS was included prospectively in these studies and comprised subject-reported diary data, including urgency (as measured using the validated Urgency Severity Scale), 24-hour voiding frequency, and UUI episode frequency. Subjects’ OAB-SCS were derived from 3-day bladder diary data collected prior to study visits at Weeks 1, 4, and 12.
Results: In total, 1165 subjects were randomized (trospium QD, 578; placebo, 587). Decreases from baseline in average daily OAB-SCS following administration of trospium QD were significant vs placebo from Week 1 and persisted to Week 12 (p<0.001; Table). Reverse stepwise analyses revealed that subjects in the trospium QD group demonstrated statistically significant reductions in OAB-SCS from baseline within Week 1 at Days 5, 6, and 7 vs the placebo group.
Table. Change in average daily OAB-SCS (ITT population; LOCF)

OAB-SCS	Placebo (n=576)	Trospium QD (n=559)	p-valuea
Baseline (Week 0)	37.46	37.10	NS
Score change from baseline (%)
Week 1	-4.47 (-10.51)	-6.52 (-16.78)	<0.001
Week 4	-6.22 (-15.32)	-9.50 (-25.03)	<0.001
Week 12	-7.17 (-17.56)	-10.55 (-28.13)	<0.001

^aRank analysis of variance model.
ITT, intent to treat; LOCF, last observation carried forward; NS, not significant.
Conclusions: Trospium QD demonstrated a statistically significant decrease in OAB-SCS from as early as Day 5 continuing through Week 12 vs placebo. Trospium QD provided rapid and sustained relief from urinary urgency, frequency and UUI - the core symptoms of OAB.
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