Efficacy and Safety of Eliapixant in Overactive Bladder: The 12-Week, Randomised, Placebo-controlled Phase 2a OVADER Study

Background: Effective, well -tolerated novel treatments for overactive bladder (OAB) are lacking. The P2X3 receptor antagonist eliapixant demonstrated potential to reduce OAB symptoms in preclinical studies. Objective: To evaluate the safety, tolerability, and efficacy of eliapixant in patients with OAB with urgency urinary incontinence (UUI). Design, setting and participants: OVADER was a 12 -wk, randomised, placebo -controlled, double-blind, parallel -group, multicentre, phase 2a study (NCT04545580) conducted between 2020 and 2022 in private and institutional clinical practices. Eligible patients were aged >= 18 yr with wet OAB symptoms (urgency, urinary frequency, and urinary incontinence) for >= 3 mo before screening. Intervention: Randomisation (1:1 ratio) to oral eliapixant 125 mg or placebo twice daily. Outcome measurements and statistical analysis: The primary endpoint was the mean change from baseline in the mean number of UUI episodes/24 h over weeks 4, 8, and 12 according to an electronic bladder diary, evaluated using a repeated -measurement model in a Bayesian framework. Results and limitations: Of 202 patients enrolled, 85 were valid for per -protocol analysis. The primary efficacy endpoint was not met. The posterior probability for eliapixant superiority over placebo was 40% (point estimate 0.05, 95% credible interval -00 to 0.38), which did not meet the predefined criterion of >= 90% probability. Secondary and exploratory endpoints were not met. The incidence of adverse events was similar in the eliapixant (n = 32, 63%) and placebo (n = 27, 56%) groups; most were mild and five led to discontinuation of eliapixant. Conclusions: OVADER did not meet its clinical efficacy endpoints. Potential reasons include the nonspecific OAB symptom complex, the poorly understood pathophysiology, and the coinciding COVID-19 pandemic.