OAB agent demonstrates efficacy, tolerability in phase III trial

The selective beta3-adrenoceptor agonist mirabegron effectively improves symptoms of overactive bladder and is very safe and well tolerated, according to results of a North American phase III study presented yesterday.

The pivotal trial was conducted at 132 sites in the U.S. and Canada and randomized 1,328 patients 1:1:1 to receive placebo, mirabegron, 50 mg, or mirabegron, 100 mg daily for 12 weeks.

Using data from patient diaries, change from baseline to final visit in the mean number of incontinence episodes per 24 hours and micturitions per 24 hours were analyzed as co-primary efficacy endpoints, and the results showed statistically significant differences favoring both mirabegron, 50 mg and 100 mg, versus placebo for both variables (incontinence: −1.47, −1.63, and −1.13, respectively; micturition: −1.66, −1.75, and −1.05, respectively).

Secondary efficacy analyses showed mirabegron was significantly more effective than placebo for reducing both micturition and incontinence frequency at the first measured time point at 4 weeks. Both doses of mirabegron were also favored over placebo in analyses of changes from baseline to final visit in volume voided/micturition, level of urgency, number of urgency incontinence episodes/24 hours, number of grade 3/4 urgency episodes/24 hours, and number of nocturia episodes/24 hours.

Rates of treatment-emergent adverse events were similar in all groups (~50%), as were study withdrawals due to adverse events (~4%). Rates of serious adverse events, dry mouth, and constipation were also low and similar in mirabegron patients and controls, and the beta3-adrenoceptor agonist was not associated with any major cardiovascular events.

Other data showed treatment benefits in patient-reported outcomes, and the objective findings are consistent with outcomes from the second phase III study conducted in Europe, Australia, and Japan, reported first author Victor W. Nitti, MD, of New York University Langone Medical Center, New York.

"With its efficacy and favorable safety profile, mirabegron appears to be a promising alternative to antimuscarinics to include in our armamentarium for OAB," Dr. Nitti said.

Dr. Nitti is a consultant/adviser to Allergan, Astellas, and Pfizer.