The efficacy and tolerability of tarafenacin, a new muscarinic acetylcholine receptor M3 antagonist in patients with overactive bladder; randomised, double-blind, placebo-controlled phase 2 study

ObjectivesTo evaluate the dose-response relationship of tarafenacin, an antimuscarinic agent in development phase, for efficacy and safety, at daily doses of 0.2 and 0.4mg for the treatment of overactive bladder (OAB) Patients and methodsThis multicentre, placebo-controlled, randomised, double-blind, phase 2b study was conducted. Patients were randomised to tarafenacin 0.2mg, tarafenacin 0.4mg or placebo daily for 12weeks. Adult patients with OAB for at least 6months, with an average of 8 micturitions per day and 3 incontinence episodes or a total of 6 urgency episodes per 3days were enrolled. The primary objective was to compare the mean changes in the number of micturitions per 24h of the two doses of tarafenacin compared with placebo from baseline to 12weeks after treatment. ResultsA total of 334 patients were screened, of whom 235 patients were randomised. The mean decrease in the number of micturitions per 24h from baseline to 12weeks was statistically higher in the tarafenacin 0.4mg group (-2.432.21 times per day, p=0.033) and non-statistically significant in the tarafenacin 0.2mg group (-1.92 +/- 2.45 times per day, p=0.393) when compared with the placebo group (-1.77 +/- 2.95 times per day). There were no statistically significant differences in the mean change of urgency episodes per 24h among three groups. The most common adverse event was dry mouth. There were no significant differences in blurred vision and constipation compared with placebo. ConclusionsTarafenacin 0.4mg decreased the number of micturitions in patients with OAB after 12weeks compared with placebo, and the dose-response relationship of tarafenacin 0.2 and 0.4mg was confirmed. Both dose levels of tarafenacin were well tolerated.