Indacaterol is a novel once-daily (qd) inhaled β2-agonist in clinical development for COPD. This study compared the bronchodilator efficacy of indacaterol and the once-daily anticholinergic bronchodilator, tiotropium.
In an incomplete-block crossover design, patients received three of four treatments: indacaterol 150 αg or 300 αg qd, tiotropium 18 αg qd or placebo, each for 14 days. Study drug was supplied daily by blinded study personnel to maintain blinding of patients and investigators. The primary efficacy variable was FEV1 at 24 h post-dose (‘trough’) after 14 days, with the study powered to show non-inferiority between indacaterol and tiotropium.
169 patients with moderate-severe COPD (mean age 65 years, post-albuterol FEV1 57% predicted, FEV1/FVC 0.50) were randomized and 153 (90.5%) completed. For trough FEV1 after 14 days, indacaterol 150 αg and 300 αg provided statistically and clinically superior bronchodilation to placebo, with differences of 170 and 150 mL respectively (p<0.001; placebo mean value 1.36 L). Trough FEV1 after 14 days was 50 and 30 mL higher than tiotropium for indacaterol 150 αg and 300 αg, respectively. Non-inferiority was demonstrated, and the trough FEV1 increment achieved with indacaterol 150 αg was significantly higher than with tiotropium (p=0.043). At 5 min post-dose on Day 1, both doses of indacaterol increased FEV1 by 130 mL from baseline, more than double the increase with tiotropium of 60 mL. Adverse events were reported by similar proportions of patients: 31.4%, 29.5%, 28.3% and 28.5% for indacaterol 150 αg, 300 αg, tiotropium and placebo treatments, respectively.
Once-daily indacaterol provided clinically relevant 24-h bronchodilation which was at least as effective as tiotropium and numerically superior. Indacaterol had a faster onset of action (within 5 min) on the first day of dosing. Adverse events were similar across groups. Results confirm previous reports of a 26-week study using open-label tiotropium.
Indacaterol should prove useful in patients with moderate and severe COPD, where treatment with one or more classes of long-acting bronchodilator is recommended.
David Ramos-Barbon, University grant monies N/A; Grant monies (from sources other than industry) N/A; Grant monies (from industry related sources) N/A; Shareholder NA; Employee DJ, SP, RO, MH & BK are Novartis employees; Fiduciary position (of any organization, association, society, etc, other than ACCP N/A; Consultant fee, speaker bureau, advisory committee, etc. CV gave presentations at symposia sponsored by (in alphabetical order) Altana, Astra Zeneca, Aventis, Bayer, Boehringer, Chiesi, Glaxo Smith Kline, Merck Darmstadt, Novartis, Pfizer, Talecris. CV received fees for consulting from (in alphabetical order) Altana, Astra Zeneca, Bayer, Boehringer, Glaxo Smith Kline, Janssen-Cilag, Talecris. DRB was a speaker at conferences sponsored by AstraZeneca, Merck Sharp&Dohme and Pfizer and received consulting fees from GlaxoSmithKline.; Other N/A; No Product/Research Disclosure Information