Critical analysis of phase 2 and 3 randomized control trials (RCTs) evaluating efficacy and tolerability of a ß3 -adrenoceptor agonist (Mirabegron) for overactive bladder (OAB).

BJU international

PubMedID: 24602031

Rossanese M, Novara G, Challacombe B, Iannetti A, Dasgupta P, Ficarra V. Critical analysis of phase 2 and 3 randomized control trials (RCTs) evaluating efficacy and tolerability of a ß3 -adrenoceptor agonist (Mirabegron) for overactive bladder (OAB). BJU Int. 2014;.
INTRODUCTION AND OBJECTIVES
A new class of oral drug inducing a direct relaxation of detrusor smooth muscle via stimulation of bladder ß3 -adrenoceptor (ß3 -AR) is currently available for the treatment of overactive bladder symptoms. The objective of the present review is to perform a critical analysis of available phase II-III RCTs reporting clinical data concerning the effectiveness and tolerability of Mirabegron in the treatment of OAB syndrome EVIDENCE ACQUISITION: A review of the literature was performed in September 2013 using the MEDLINE database. A ''free text'' protocol was employed for the search strategy using "overactive bladder" and "Mirabegron" as key words. Subsequently, the searches were pooled and limited to phase II and III RCTs.

EVIDENCE SYNTHESIS
Two phase II randomized controlled trials (RCTs) and 5 phase III RCTs were selected and analyzed. Available phase II studies demonstrated the efficacy and tolerability of different doses of Mirabegron compared with the placebo. Moreover, a dose-ranging study demonstrated that 50 mg once daily should be considered the most promising dose for clinical use. 12-weeks phase III studies confirmed the efficacy of Mirabegron to significantly reduce the mean number of incontinence episodes per 24 hours and the mean number of micturitions per 24 hours in comparison with placebo. A post-hoc analysis confirmed that favourable results with Mirabegron were reported both in OAB patients who were antimuscarinic naïve and who had discontinued prior antimuscarinic therapy. Moreover, a phase III trial demonstrated the safety and tolerability of 12-mo treatment of Mirabegron. Discontinuation due to adverse events was low both using 50 and 100 mg dose of Mirabegron.

CONCLUSIONS
Mirabegron is the first of a new class of drugs for the treatment of OAB able to influence non-voiding activity and producing an increased storage capacity and inter-void interval. Recently published phase 2 and 3 RCTs demonstrated that the ß3 -adrenoceptor selective agonist Mirabegron is an effective and safe drug for the symptomatic treatment of OAB syndrome. Mirabegron represents a valid medical option both for naïve OAB patients as well as in those where antimuscarinics are ineffective or not tolerated.