Tolerability of indacaterol, a novel once-daily beta2-agonist, in patients with asthma: a randomized, placebo-controlled, 28-day safety study.

Abstract

BACKGROUND:

Indacaterol is a novel, inhaled, once-daily beta2-agonist.

OBJECTIVE:

To investigate the safety and tolerability of indacaterol at doses of 400 and 800 microg/d.

METHODS:

Randomized, double-blind, placebo-controlled, parallel-group, multicenter, 28-day study. Patients with persistent asthma (forced expiratory volume in 1 second [FEV1] > or =-60% predicted, < or =1,600 microg of beclomethasone dipropionate or equivalent daily) received indacaterol, 400 microg (n = 59) or 800 microg (n = 59), or placebo (n = 26) once daily via a single-dose dry powder inhaler. Safety assessments were performed before and after dosing on days 1, 14, and 28, with particular attention to key beta2-agonist safety variables.

RESULTS:

A total of 144 patients were randomized, with 135 (93.8%) completing the study. Indacaterol was well tolerated: the incidence of adverse events (AEs) was similar between the active and placebo groups, and AEs, when they occurred, were mild or moderate for most (98.2%). There was no dose-response relationship between indacaterol and the incidence of AEs (400 microg, 40.7%; 800 microg, 37.3%; and placebo, 38.5%). Few AEs considered as beta2-agonist class effects occurred (none leading to withdrawal). Small differences between indacaterol and placebo in mean serum potassium (< or =-0.29 mmol/L) and glucose (< or =0.93 mmol/L) levels were occasionally statistically significant (P < .05) but not regarded as clinically meaningful. As expected for a beta2-agonist, there was some indication of a trend in QTc prolongation with increasing exposure (maximum mean change, 8.9 milliseconds; P < .05 vs placebo). Significant increases in FEV1 (P < .05) were seen at all postbaseline time points for both indacaterol doses vs placebo, with indacaterol-placebo differences 30 minutes after dosing of 0.21 to 0.25 L and before dosing on days 14 and 28 (approximately 24 hours after the previous dose) of 0.15 to 0.23 L.

CONCLUSION:

Indacaterol had a good overall safety profile and was well tolerated at both doses, with predose FEV1 results on days 14 and 28 indicating 24-hour bronchodilator efficacy.

• Authors: William H Yang, Jean Benoit Martinot, Petr Pohunek, Jutta Beier, Daniel Magula, Ray Cameron, Roger Owen, Mark Higgins
• Journal: Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (Ann Allergy Asthma Immunol) Vol. 99 Issue 6 Pg. 555-61 (Dec 2007) ISSN: 1081-1206 [Print] United States
• PMID: 18219838 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic beta-Agonists
• Blood Glucose
• Indans
• Quinolones
• indacaterol
• Potassium

Topics

• Adolescent
• Adrenergic beta-Agonists (administration & dosage, adverse effects)
• Adult
• Aged
• Asthma (blood, drug therapy, physiopathology)
• Blood Glucose (metabolism)
• Child
• Double-Blind Method
• Drug Administration Schedule
• Electrocardiography (drug effects)
• Female
• Forced Expiratory Volume (drug effects)
• Heart Rate (drug effects)
• Humans
• Indans (administration & dosage, adverse effects)
• Male
• Middle Aged
• Potassium (blood)
• Quinolones (administration & dosage, adverse effects)