Estudio de indacaterol en epoc

Allergology International. 2010;59:
DOI: 10.2332! allergolint.10-OA-0173

-

ORIGINAL ARTICLE

Bronchodilator Efficacy of Single Doses of Indacaterol in Japanese Patients with COPD: A Randomised, Double-Blind, Placebo-Controlled Trial
Motokazu Kato1, Hironi Makita2, Koji Uemura3, Yoshinosuke Fukuchi4, Motoi Hosoe5, Charlotte Emery6, Mark Higgins6 and Benjamin Kramer7
ABSTRACT Background:Indacaterol is an investigational, novel, inhaled once-daily ultra-long-acting beta-2 agonist for
the treatment of chronic obstructive pulmonary disease (COPD). This study evaluated the 24-h bronchodilatory efficacy and safety of indacaterol in Japanese patients with COPD. Methods: This Phase-II, randomised, placebo-controlled, crossover study comprised four double-blind, single-dose treatmentperiods (washout between periods: 14-28 days). Japanese patients aged 40-75 years with moderate-to-severe COPD were randomised to receive single doses of indacaterol (150, 300, or 600 μg) or placebo via a single-dose dry-powder inhaler. Efficacy (primary endpoint: standardised FEV1AUC22-24h) and safety were assessed for 24 h post-dose in each treatment period. Results: Of the 50 patients randomised(92% male; mean age, 67.2 years), 45 completed the study. Standardised FEV1AUC22-24h was significantly higher for all indacaterol doses as compared with placebo, with clinically relevant differences of 130, 160, and 170 mL for 150, 300, and 600 μg, respectively (P < 0.001). The improvement in FEV1 was seen as early as 5 min post-dose with indacaterol and sustained for 24 h (P < 0.001 vs placeboat all time points). All indacaterol doses were well tolerated and showed no clinically meaningful effect on pulse rate, blood pressure, QTc interval, and laboratory parameters when compared with placebo. Conclusions: In the Japanese COPD population studied, single doses of indacaterol (150, 300, and 600 μg) provided sustained 24-h bronchodilation, with onset of action within 5 min post-dose. Alldoses were well tolerated. These results are consistent with data from Caucasian populations.

KEY WORDS
beta2-agonists, bronchodilator, COPD, efficacy, indacaterol

INTRODUCTION
Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality
City Hospital, Osaka, 2Makita Hospital, 3Kita 13-jo Naika Clinic, Hokkaido, 4Juntendo University, 5Novartis PharmaKK, Tokyo, Japan, 6Novartis Horsham Research Centre, Horsham, West Sussex, UK and 7Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. Authors’ contributions: MK, HM, KU and YF were involved in the acquisition and interpretation of data. MHo and MHi contributed to the study design, oversaw the conduct of the study and were involved in the analysis and interpretation of the data. CEcontributed to the study design (including the statistical methodology), and analysis and interpretation of data. BK oversaw the conduct,
1Kishiwada

worldwide, accounting for a loss of approximately 30 million disability-adjusted life years in 2001.1 The prevalence of COPD in Japan in adults aged "40 years is estimated to be at least 8.6%.2 The increase in
analysis, and interpretation of data. Allauthors substantially contributed in drafting and revision of the manuscript for important intellectual content and have read and approved the final manuscript. Correspondence: Motoi Hosoe, Novartis Pharma KK, 4−17−30 Nishi-Azabu, Minato-ku, Tokyo 106−8618, Japan. Email: motoi.hosoe@novartis.com Received 6 January 2010. Accepted for publication 11 March 2010. !2010 Japanese Society of AllergologyAllergology International Vol 59, No3, 2010 www.jsaweb.jp!

1

Kato M et al.

Randomisation Washout Period I

Washout

Washout Period IV

METHODS
This was a multicentre, randomised, double-blind, placebo-controlled, crossover, dose-ranging, Phase II study conducted between December 2006 and October 2007 at 11 specialised respiratory care units in Japan (ClinicalTrials.gov...