Safety and tolerability of indacaterol in asthma: A randomized, placebo-controlled 28-day study

Abstract

The safety and tolerability of indacaterol, a novel once-daily beta(2)-agonist bronchodilator with a fast onset of action, were assessed in 156 asthma patients in a multicentre, randomized, double-blind, placebo-controlled study. Patients received indacaterol 200, 400 or 600 microg or placebo once daily for 28 days. Adverse events (AEs), laboratory assessments, vital signs, electrocardiograms, spirometry and physical examinations were monitored. Indacaterol pharmacokinetics were assessed. There was no evidence of dose-related increases in AE incidence or clinically significant hypokalaemia or hyperglycaemia in indacaterol-treated patients. Mean pulse rate changes were minor in any group, with maximum 1-h post-dose changes from baseline of -3.7, -3.3 and -2.2 bpm for indacaterol 200, 400 and 600 microg, respectively, and -2.9 bpm for placebo. Mean QTc interval was similar between groups; change from baseline >60 ms occurred in only two patients. Mean FEV(1) increased after the first indacaterol dose; baseline-adjusted pre-dose (trough) values remained >or=166 mL higher than placebo at all subsequent visits, supporting a 24-h bronchodilator effect. Pre-dose (but not post-dose) serum indacaterol concentrations indicated a slight trend for accumulation. Once-daily indacaterol 200-600 microg has a favourable therapeutic index. It is well tolerated, and is not associated with any adverse cardiac or metabolic effects, while providing effective 24-h bronchodilation.

Indacaterol: a new once daily long-acting beta2 adrenoceptor agonist

“…Of the doses evaluated, 200 mcg once daily appeared to be optimum as shown by trough FEV 1 24 hours postdose on days 1 and 7. This was further supported by a multiple-dose, dose-ranging study by Kanniess et al18 and a 28-day safety study by Chuchalin et al 19 Finally, indacaterol 200 mcg was also superior to salbutamol 200 mcg and salmeterol 50 mcg in a single-dose study in persistent asthmatics20 Peak bronchodilation in these studies was observed between 2–4 hours postdose.…”

“…However, in the study by Yang et al26 only few patients had potassium or glucose levels outside the normal range. In the study by Chuchalin et al19 in asthmatics, no effect of once daily indacaterol 200, 400, and 600 mcg on potassium and glucose levels was observed. In this study, there were also no changes in pulse rate, blood pressure, or mean QTc interval after 28 days’ exposure to indacaterol.…”

“…The most common adverse event associated with indacaterol use was cough, which was reported in 16.9% and 15.3% of patients in the indacaterol 400 and 800 mcg groups, respectively, in the study by Yang et al 26 in 8.1%, 17.1%, and 10.3% of patients in the indacaterol 600, 400, and 200 mcg groups, respectively, in the study by Chuchalin et al19 and finally in 14.7% and 28.4% of patients in the 400 and 800 mcg groups, respectively, in the study by Beier et al25 This cough was, however, mild in severity, transient in nature and duration, and tended to decline with the duration of treatment. Further, treatment-associated cough did not lead to discontinuation of the study in any patients.…”

“…Three trials primarily evaluating safety and tolerability of indacaterol have been published, two in asthma,19,26 and one in COPD 25. All three trials incorporated a treatment duration of 28 days.…”

Emerging inhaled bronchodilators: an update

“…The safety and tolerability of indacaterol were assessed in 156 asthma patients in a multicentric randomised double-blind placebo-controlled study [21]. Patients received 200, 400 or 600 mg indacaterol or placebo once daily for 28 days.…”