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

Abstract

Background: A dose-finding study was performed as the first step in the clinical development of the new drug, cizolirtine citrate.

Objective: To assess the efficacy and safety of cizolirtine citrate in overactive bladder with urinary incontinence.

Design, setting, and participants: 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.

Interventions: Patients received cizolirtine citrate 400 mg bid (C400), cizolirtine citrate 200 mg bid (C200), or placebo.

Measurements: 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.

Results and limitations: 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.

Conclusions: The therapeutic potential of cizolirtine citrate 400mg bid in overactive bladder has been evidenced.