A Randomised, Double-blind, Placebo-controlled Phase II Study to Investigate the Efficacy and Safety of the EP-1 Receptor Antagonist, ONO-8539, in Patients with Non-Neurogenic Overactive Bladder Syndrome
Chapple CR, Abrams P, Andersson KE, Radziszewski P, Masuda T, Small M, Kuwayama T, Deacon S. J Urol. 2013 Sep 6. pii: S0022-5347(13)05329-9. doi: 10.1016/j.juro.2013.08.082. [Epub ahead of print]

Source

Royal Hallamshire Hospital, Sheffield, UK. Electronic address: c.r.chapple@sheffield.ac.uk.

Abstract

PURPOSE:

To evaluate for the first time the efficacy, safety and tolerability of ONO-8539, an EP1 receptor antagonist, in patients with overactive bladder (OAB) syndrome.

MATERIALS AND METHODS:

Twelve-week, randomised, double-blind, placebo-controlled, parallel-group, multicentre study with a 2-week single-blind placebo run-in phase. Patients (n=435) were randomised to receive twice-daily ONO-8539 (30 mg, 100 mg, 300 mg), placebo or once-daily tolterodine 4 mg.

RESULTS:

At the end of the 12-week treatment, no statistically significant difference was found between ONO-8539 and placebo for change from baseline in number of micturitions/24 hours (primary endpoint; ONO-8539 30 mg: -1.02; 100 mg: -1.53; 300 mg: -1.31; placebo: -1.40). There were no statistically significant differences between any ONO-8539 group and placebo for change from baseline in the number of urgency episodes/24 hours, urinary urgency incontinence episodes/24 hours and mean volume voided/micturition (secondary endpoints). Statistically significant differences for tolterodine versus placebo were observed for change from baseline in the number of micturitions (p=0.045), urgency episodes (p=0.04) and mean volume voided/micturition (p<0.001). The percentage of adverse events was 54.1% in the placebo group, 43.0-54.0% in the ONO-8539 groups and 46.6% in the tolterodine group. The intensity of adverse events was similar between treatment groups. The most frequently reported adverse events after ONO-8539, similar to other treatments, were nasopharyngitis and diarrhoea.

CONCLUSIONS:

The results of this study, which evaluated ONO-8539 for the first time in patients with OAB, suggest a minimal role for EP1 receptor antagonism in the management of patients with OAB syndrome.