Cizolirtine citrate, an effective treatment for symptomatic patients with urinary incontinence secondary to overactive bladder: a pilot dose-finding study.

Abstract

A dose-finding study was performed as the first step in the clinical development of the new drug, cizolirtine citrate. To assess the efficacy and safety of cizolirtine citrate in overactive bladder with urinary incontinence. Seventy-nine outpatients with clinical overactive bladder and/or urodynamic diagnosis of detrusor overactivity were randomized in a multicentre, 12-wk, double-blind, pilot trial. Patients received cizolirtine citrate 400 mg bid (C400), cizolirtine citrate 200 mg bid (C200), or placebo. Patients recorded efficacy variables in 7- and 14-d bladder diaries: urinary incontinence episodes, voluntary micturitions, and urgency episodes. The primary efficacy endpoints were changes from baseline to week 12 in average 24-h frequencies of the efficacy variables. Average 24-h frequency of urinary incontinence episodes decreased by a median of 1.14 in C400 versus 0.21 in placebo (p=0.08). Urgency episodes decreased by a median of 3.00 in C400, by 1.29 in C200 and by 0.43 in placebo (p=0.004; C400 vs placebo). Cizolirtine showed a clear improvement regarding the percentage of patients free from urinary incontinence episodes at the end of the study, being 68.75% in C400, 45% in C200, and 30% in placebo (p=0.04; C400 vs placebo). The global efficacy assessment reported by patients showed a clearly favourable opinion ("excellent" or "good") given by 80% of the patients in C400 and 60% in C200 versus 39% in placebo. Patients reporting adverse events (AEs) were 37% in placebo, 68% in C200, and 81% in C400. The majority of AEs had mild to moderate severity and none was serious. The therapeutic potential of cizolirtine citrate 400mg bid in overactive bladder has been evidenced.