Multicenter, Randomized, Double-Blind, Parallel, Active Control, Phase III Clinical Study to Assess the Efficacy and Safety of THVD-201 (Combination of Tolterodine and Pilocarpine) in Patients with Overactive Bladder Including an Open-Label, Extension Study.

Purpose: We evaluated the efficacy and safety of a combination of 2 mg tolterodine and 9 mg pilocarpine, vs tolterodine monotherapy in patients with overactive bladder. Materials and Methods: We enrolled patients with overactive bladder symptoms in a multicenter, randomized, double-blind, parallel, active control study. Patients were randomized to the combination or 2 mg tolterodine twice daily for 12 weeks. After the double-blind period finished all patients were started on the combination for 12 weeks. Study co-primary end points were the change from baseline in the mean number of daily micturitions and cumulative incidence of dry mouth at the end of 12 weeks. Secondary end points were other overactive bladder symptoms, the total xerostomia inventory score and results of a visual analogue scale for dry mouth at the end of 12 and 24 weeks. Results: The mean change in the number of daily micturitions from baseline to 12 weeks was -1.49 and -1.74 in the combination and tolterodine monotherapy groups, respectively. The mean difference was -0.26 (95% CI -0.79-0.27), confirming noninferiority. At 12 weeks the incidence of dry mouth was lower in the combination group than in the tolterodine monotherapy group (30.0% vs 42.9%, p = 0.009). All secondary and other efficacy outcomes related to overactive bladder symptoms improved in each group with no significant differences between the groups at 12 weeks. Changes from baseline in the total xerostomia inventory score and the visual analogue scale for dry mouth were significantly lower in the combination group than in the tolterodine monotherapy group. Conclusions: Tolterodine and pilocarpine alleviated dry mouth in patients with overactive bladder while maintaining anticholinergic efficacy similar to that of tolterodine.