Once-daily indacaterol 75 μg in moderate- to-severe COPD: results of a Phase IV study assessing time until patients’ perceived onset of effect

Abstract

Background

Indacaterol 75 μg once daily is a long-acting β₂ agonist approved for maintenance bronchodilator treatment in patients with chronic obstructive pulmonary disease (COPD). The purpose of this study was to evaluate patients’ perception of onset of effect with a single dose.

Methods

In this double-blind, crossover, Phase IV study, 40 patients were randomized to receive a single dose of indacaterol 75 μg or placebo via a dry powder inhaler device. The primary variable was time until patient’s perception of onset of effect, using a simple self-administered (nonvalidated) questionnaire that patients answered at nine protocol-specified time points. Exploratory variables included change in forced expiratory volume in 1 second (FEV₁) and change in percent predicted FEV₁ from predose to postdose (determined 60–75 minutes postdose).

Results

The least-squares mean time to patient’s perception of onset of effect was 25.4 minutes and 23.9 minutes for indacaterol and placebo, respectively. There was no significant effect for treatment, period, or sequence on the time to patient’s perception. In addition, no statistically significant differences between treatments were observed for patient’s global satisfaction with onset of effect and global expectation of treatment adherence. For the exploratory variable change in FEV₁ from predose to postdose, indacaterol showed superiority over placebo with a clinically relevant least-squares mean treatment difference of 0.12 L (P<0.0001). There was little or no association between patient’s perception of time to onset of effect and change in FEV₁, or change in percent predicted FEV₁. Both treatments were well tolerated.

Conclusion

A single dose of indacaterol 75 μg did not separate from placebo in terms of patient perception of onset, although there was an improvement in FEV₁ for indacaterol compared with placebo. Development and use of a validated questionnaire may be needed to address the inconsistency in evaluating this patient-related outcome.

Keywords:

• bronchodilator
• long-acting
• perceived onset of action
• single dose

Acknowledgments

The authors thank the patients and staff at the participating study centers and David Young (Novartis, Horsham, UK) for critically reviewing the manuscript. The study was funded by Novartis Pharmaceuticals Corporation (East Hanover, NJ, USA); Anneliese LaRose was the clinical trial lead. Melanie Stephens, a professional medical writer (CircleScience, London, UK) funded by Novartis Pharmaceuticals Corporation, assisted in the preparation of the manuscript.

Disclosure

Thomas M Siler has received research support from Arena, Boehringer Ingelheim, Daiichi Sankyo, Dey Laboratories, Forest Research Institute, Genentech, GlaxoSmithKline, Johnson and Johnson, Merck, Novartis, Pearl Therapeutics, Schering, and Sunovion, and has received honoraria from AstraZeneca, Boehringer Ingelheim, Forest, Novartis, and UCB. Craig F LaForce is a consultant to Novartis and has received honoraria from Merck and Co. He is the principal investigator on trials with the following pharmaceutical companies: Array, Boehringer Ingelheim, GlaxoSmithKline, Merck Research Laboratories, Novartis, Pfizer, Roxane Laboratories, Teva, Sunovion, and Watson Pharmaceuticals. Selwyn Spangenthal has received honoraria from AstraZeneca, Forest, Mylan Labs, and Novartis. Farid Kianifard and James Williams are employees of Novartis Pharmaceuticals.