Indacaterol is a novel once-daily (qd) inhaled β2-agonist in development for COPD. This study evaluated long-term safety and efficacy of two doses of indacaterol versus placebo.
This was the third stage of a three-part adaptive, seamless, randomized, double-blind, parallel-group study. Following stage 1, an independent committee selected two of four indacaterol doses based on 2-week efficacy and safety data versus placebo, tiotropium and formoterol. In stage 2, the selected doses of indacaterol (150 and 300μg qd), placebo and open-label tiotropium were continued to 26 weeks. (Data from stages 1 and 2 have been reported previously: AJRCCM 2009;179:A4543/A4547.) In stage 3, indacaterol 150 or 300μg or placebo was inhaled once-daily for a further 26 weeks. Safety assessments included adverse events (AEs), electrocardiograms and laboratory evaluations. Efficacy assessments included 24-h post-dose (‘trough’) FEV1 after 52 weeks.
Stage 3 included 414 subjects (age 63 years) with moderate-severe COPD; 88% completed. Safety results are presented for indacaterol 150μg, 300μg and placebo, respectively. The overall AE incidence was 77%, 77% and 69%, with serious AEs in 10%, 13% and 11% of patients. For serum potassium, the frequency of changes from normal (at study start) to low (at any timepoint across the 52-week treatment period) was 4%, 9%, 10%. For blood glucose changes from normal to high (26%, 29%, 22%), frequencies were similar with indacaterol and placebo. There were two deaths, one each in placebo and indacaterol 300 μg groups, both due to myocardial infarction. There were no notable differences in newly occurring or worsening notable QTc values for indacaterol (6.9% 6.2% for 150 and 300μg) versus placebo (8.9%). Trough FEV1 after 52 weeks of treatment was 1.44 and 1.45L with indacaterol 150 and 300μg, respectively, clinically relevant differences from placebo of 170 and 180mL (both p<0.001).
Once-daily indacaterol provided clinically useful bronchodilation over 1 year with a safety profile similar to placebo.
Once-daily indacaterol should prove useful in the maintenance treatment of moderate-severe COPD.
Stephen Rennard, University grant monies N/A; Grant monies (from sources other than industry) N/A; Grant monies (from industry related sources) SIR and KRC have received research grants and fees from Novartis for consultancy/advisory boards and speaking, and have similar relationships with other pharmaceutical companies.; Shareholder NA; Employee AL, JS, CL, RO and BK are Novartis employees.; Fiduciary position (of any organization, association, society, etc, other than ACCP N/A; Consultant fee, speaker bureau, advisory committee, etc. N/A; Other N/A; No Product/Research Disclosure Information