Staskin DR, ¹ Sand PK, ² Zinner NR ³

¹New York Presbyterian Hospital, Weill-Cornell Medical College, New York, NY; ²Feinberg School of Medicine, Northwestern University, Chicago, IL; ³UCLA School of Medicine, Los Angeles, CA

Introduction and Objectives: An extended-release formulation of trospium chloride (trospium XR) has recently been studied for the once-daily (QD) treatment of overactive bladder (OAB). The purpose of this multicenter trial was to investigate the safety, efficacy, and tolerability of trospium XR 60 mg QD in subjects with OAB with an urgency urinary incontinence (UUI) component.

Methods: Subjects with OAB and UUI were randomized (1:1) to receive trospium XR 60 mg once daily (QD) or placebo in this 12-week, multicenter, parallel-group, double-blind, placebo-controlled trial. The primary endpoints were change in the number of toilet voids/day and change in the number of UUI episodes/day. Secondary endpoints included UUI episodes/week, urgency severity associated with voids, volume voided/void, frequency of daily urgency voids, and OAB-Symptom Composite Score. Safety parameters collected during the study included clinical laboratory tests,
12-lead electrocardiograms, spontaneously reported adverse events, and vital signs.

Results: A total of 601 participants were randomized to receive trospium XR (n=298) or placebo (n=303). Trospium XR was associated with statistically significant improvements in both primary efficacy outcomes from as early as Week 1, with progressive improvement to Week 12. Subjects treated with trospium XR experienced a reduction in the mean number of daily voids from 12.8 at baseline to <10 at Week 12 (p<0.001). Similarly, subjects treated with trospium XR experienced a reduction in the mean number of daily UUI episodes from >4 at baseline to <2 at Week 12 (p<0.01). These improvements in the primary efficacy outcomes were reflected in the analysis of “normalization” (defined as no UUI episodes and a void frequency of ≤8 voids/day), such that nearly twice as many subjects treated with trospium XR (20.5%) achieved “normalization” at Week 12 (p<0.01) compared with those receiving placebo (11.3%). Treatment with trospium XR also resulted in significant benefits compared with placebo in the secondary outcome parameters as early as Week 1 onwards. Trospium XR was well tolerated. Dry mouth was reported in 8.7% versus 3% and constipation in 9.4% versus 1.3% of subjects administered trospium XR versus placebo, respectively. Central nervous system adverse effects, such as headache and dizziness, were reported with a higher incidence in the placebo group than in the trospium XR group.

Conclusions: Trospium XR provided early and sustained improvements in the key symptoms of OAB. Typical anticholinergic adverse events occurred at considerably lower levels with trospium XR than reported previously with twice-daily (BID) trospium, while efficacy remained comparable between the two formulations. Thus, in addition to the convenience of once-daily dosing, trospium XR maintained efficacy and improved tolerability compared with trospium BID and in this study demonstrated the lowest dry mouth rate of any current oral medication for OAB.

Acknowledgments: This study was supported by Esprit Pharma and Indevus Pharmaceuticals Inc.

UroToday.com Coverage of SUFU 2007

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