Mirabegron did not prolong the QTcI interval at 50-mg or 100-mg doses in either sex, but the 200-mg supratherapeutic dose prolonged QTcI in females (upper one-sided 95% CI >10 ms).
RCT (n=352)
Double-blind
eight treatment sequences
Does mirabegron cause QTcI prolongation in healthy subjects?
Mirabegron does not prolong the QTc interval at therapeutic (50 mg) or supratherapeutic (100 mg) doses, though it may cause prolongation at 200 mg in females.
Potential effects of the selective β(3)-adrenoceptor agonist mirabegron on cardiac repolarization were studied in healthy subjects. The four-arm, parallel, two-way crossover study was double-blind and placebo- and active (moxifloxacin)-controlled. After 2 baseline ECG days, subjects were randomized to one of eight treatment sequences (22 females and 22 males per sequence) of placebo crossed over with once-daily (10 days) 50, 100, or 200 mg mirabegron or a single 400-mg moxifloxacin dose on day 10. In each period, continuous ECGs were recorded at two baselines and on the last drug administration day. The lower one-sided 95% confidence interval for moxifloxacin effect on QTcI was >5 ms, demonstrating assay sensitivity. According to ICH E14 criteria, mirabegron did not cause QTcI prolongation at the 50-mg therapeutic and 100-mg supratherapeutic doses in either sex. Mirabegron prolonged QTcI interval at the 200-mg supratherapeutic dose (upper one-sided 95% CI >10 ms) in females, but not in males.
Malík et al. (Wed,) conducted a rct in Healthy subjects (n=352). Mirabegron vs. Placebo and moxifloxacin was evaluated on QTcI prolongation. Mirabegron did not prolong the QTcI interval at 50-mg or 100-mg doses in either sex, but the 200-mg supratherapeutic dose prolonged QTcI in females (upper one-sided 95% CI >10 ms).