Prolonged bronchoprotection against inhaled methacholine by inhaled BI 1744, a long-acting β2-agonist, in patients with mild asthma - 12/08/11
, Just van der Linde, MD a, Donald W. Cockcroft, MD, FRCP(C) c, Gail M. Gauvreau, PhD a, John D. Brannan, PhD a, Mark FitzGerald, MD, FRCP(C) d, Richard M. Watson, BSc a, Joanne Milot, BSc b, Beth Davis, PhD c, Megan O’Connor, RN a, Lorna Hart, PhD e, Lawrence Korducki, MSc e, Alan L. Hamilton, PhD e, Louis-Philippe Boulet, MD, FRCP(C) b
Reprint requests: Paul M. O’Byrne, MB, FRCP(C), Department of Medicine, McMaster University Medical Center, 1200 Main St West, Hamilton, Ontario, Canada.Abstract |
Background |
Long-acting ß2-agonists are an established controller medication in asthma. BI 1744 is a novel L\long-acting ß2-agonist with a preclinical profile that suggests 24-hour bronchodilation and bronchoprotection may be achieved.
Objective |
To examine the bronchoprotective effects of single doses of BI 1744 against methacholine provocation in subjects with mild asthma.
Methods |
Thirty-one subjects with mild asthma were randomized to receive single doses of BI 1744 (2, 5, 10, 20 μg) or placebo on separate days according to a double-blind, 5-way crossover design. Methacholine challenges were performed at 30 minutes and at 4, 8, 24, and 32 hours after each single dose of medication, and the results were expressed as PC20 FEV1.
Results |
All doses of BI 1744 produced statistically significant increases in the methacholine PC20 compared with placebo as long as 32 hours. The mean (geometric SEM) methacholine PC20 24 hours after dosing with placebo was 1.73 (1.13) mg/mL, which increased after 2 μg to 3.86 (1.14) mg/mL, after 5 μg to 5.67 (1.14) mg/mL, after 10 μg to 9.42 (1.13) mg/mL, and after 20 μg to 13.71 (1.14) mg/mL (all P < .0001). After 32 hours, the methacholine PC20 value remained significantly increased for all doses. No safety or tolerability concerns were identified.
Conclusion |
BI 1744 provides significant bronchoprotection against inhaled methacholine for up to 32 hours after single-dose administration.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, long-acting inhaled β2-agonists, methacholine, functional antagonists, bronchodilators
Abbreviations used : AE, LABA
Plan
| Supported as part of the AllerGen Network of Centers of Excellence Clinical Investigator Collaborative and by Boehringer Ingelheim Inc. |
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| Disclosure of potential conflict of interest: P. M. O’Byrne is on the advisory board for AstraZeneca, GlaxoSmithKline, Topigen, Wyeth, and Schering; receives speakers’ honoraria from AstraZeneca and GlaxoSmithKline; and receives research support from AstraZeneca, GlaxoSmithKline, Merck, Wyeth, Schering, and Alexion. D. W. Cockcroft received a travel grant from Merck; receives honoraria from GlaxoSmithKline; is a consultant for Pharmoxis; receives research support from AllerGen, Wyeth Pharmaceuticals, and Genentech; and is a member of the ATS, CTS, CSACI, ACAAI, and ACCP. G. M. Gauvreau receives honoraria from Boehringer Ingelheim and Schering Plough and research support from Schering Plough, MedImmune, and Genentech. M. FitzGerald is on advisory boards for GlaxoSmithKline, AstraZeneca, Novartis, Pfizer, Boehringer Ingelheim, Altana, Merck, and Topigen; is on the speakers’ bureau for GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Pfizer, and Merck; receives research support from CIHR, AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Merck, Wyeth, Schering, Genentech, and Topigen; is a member of the GINA Executive Committee and CTS Asthma Committee; and is Chair of the GINA Science Committee. L.-P. Boulet is on advisory boards for AstraZeneca, Altana, GlaxoSmithKline, Merck Frosst, and Novartis; receives lecture fees from 3M, Altana, AstraZeneca, GlaxoSmithKline, Merck Frosst, and Novartis; receives research support from AstraZeneca, GlaxoSmithKline, Merck Frosst, Schering, 3M, Altana, AsthmaTx, Boehringer Ingelheim, Dynavax, Genentech, IVAX, MedImmune, Novartis, Roche, Topigen, and Wyeth; is an advisor for the Conseil du Medicament du Quebec; is a member of the Quebec Workmen Compensation Board Respiratory Committee; is chair of the Canadian Thoracic Society Guidelines Dissemination and Implementation Committee; is coleader of the Therapeutics Theme of the Canadian AllerGen Network of Centers of Excellence; is the holder of the Laval University Chair on Knowledge Transfer, Prevention, and Education in Respiratory and Cardiovascular Health; and is a member of the Asthma Committee of the World Allergy Organization. L. Hart, L. Korducki, and A. L. Hamilton are employed by Boehringer Ingelheim. The rest of the authors have declared that they have no conflict of interest. |
Vol 124 - N° 6
P. 1217-1221 - décembre 2009 Retour au numéro
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