Cardiac safety of indacaterol in healthy subjects: a randomized, multidose, placebo- and positive-controlled, parallel-group thorough QT study
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Khindri, Sanjeev, Woessner, Ralph, Sabo, Ronald, Drollmann, Anton Franz, Harris, Stuart and Jennings, Simon (2011) Cardiac safety of indacaterol in healthy subjects: a randomized, multidose, placebo- and positive-controlled, parallel-group thorough QT study. BMC Pulmonary Medicine, 11. p. 31. ISSN 1471-2466
Abstract
Background
Indacaterol is a novel once-daily ultra long-acting β2-agonist for the treatment of chronic obstructive pulmonary disease. It is known that β2-agonists, like other adrenergic compounds, can prolong the QT-interval. This thorough QT/QTc study (as per ICH E14 guideline) evaluated the effect of indacaterol on the QT interval in healthy subjects.
Methods
In this randomized, double-blind, parallel-group, placebo- and positive-controlled (open-label moxifloxacin) study, non-smoking healthy subjects (18–55 years, body mass index: 18.5–32.0 kg/m2) were randomized (4:4:2:4:1) to 14-day treatment with once-daily indacaterol (150 µg, 300 µg, or 600 µg), placebo, or placebo/moxifloxacin (double-blind 14-day treatment with placebo and a single open-label dose of 400 mg moxifloxacin on Day 14). The primary endpoint was the change from baseline on Day 14 in QTcF (QT interval corrected for heart rate using Fridericia’s formula).
Results
In total, 404 subjects were randomized to receive indacaterol (150 [n=108], 300 [n=108], 600 µg [n=54]), placebo (n=107), or placebo/moxifloxacin (n=27); 388 subjects completed the study. Maximal time-matched mean (90% confidence intervals) treatment differences from placebo in QTcF change from baseline on Day 14 were 2.66 (0.55, 4.77), 2.98 (1.02, 4.93) and 3.34 (0.80, 5.82) ms for indacaterol 150 µg, 300 µg and 600 µg, respectively. Study sensitivity was confirmed with moxifloxacin demonstrating a significant maximal time-matched QTcF prolongation of 13.90 (10.58, 17.22) ms compared to placebo. All indacaterol doses were well tolerated.
Conclusion
Indacaterol, at doses up to 600 μg once daily (2–4 times the therapeutic dose) does not have any clinically relevant effect on the QT interval.
| Item Type: | Article |
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| Date Deposited: | 13 Oct 2015 13:15 |
| Last Modified: | 13 Oct 2015 13:15 |
| URI: | https://oak.novartis.com/id/eprint/3893 |