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


METHODS
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.


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


METHODS
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.


CONCLUSIONS
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.
Martínez-García
Roberto
R
Hospital Clínico, Universidad de Valencia, Spain.
Abadías
Montserrat
M
Arañó
Pere
P
Perales
Lorenzo
L
Ruíz
José Luis
JL
Sust
Mariano
M
Conejero
Juan
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015740:Calcitonin Gene-Related Peptide / Q000187:drug effects / Q000378:metabolism; D004244:Dizziness / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D010865:Pilot Projects; D011720:Pyrazoles / Q000008:administration & dosage*; D013373:Substance P / Q000187:drug effects / Q000378:metabolism; D053201:Urinary Bladder, Overactive / Q000150:complications / Q000188:drug therapy*; D014549:Urinary Incontinence / Q000188:drug therapy* / Q000209:etiology; D014563:Urodynamics / Q000187:drug effects; D014786:Vision Disorders / Q000139:chemically induced; D014839:Vomiting / Q000139:chemically induced; D055815:Young Adult
D011720:Pyrazoles; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide; C075798:cizolirtine