Onset of action of formoterol versus salmeterol via dry powder inhalers in moderate chronic obstructive pulmonary disease: a randomized, placebo-controlled, double-blind, crossover study.

Abstract

BACKGROUND:

Bronchodilator therapy is central to the symptomatic management of chronic obstructive pulmonary disease (COPD), and treatment with short-acting bronchodilators is recommended in patients with mild COPD.

OBJECTIVE:

This study aimed to evaluate the onset of effect of single-dose formoterol 9 μg versus single-dose salmeterol 50 μg in patients with moderate COPD.

METHODS:

In this multicentre, double-blind, double-dummy, placebo-controlled, three-way single-dose crossover study, patients ≥40 years of age with moderate COPD were randomized to single-dose formoterol 9 μg via Turbuhaler® plus placebo via Diskus®, single-dose salmeterol 50 μg via Diskus® plus placebo via Turbuhaler® or placebo via Turbuhaler® and Diskus® (washout period 2-7 days). Terbutaline 0.5 mg/actuation via Turbuhaler® was used as reliever medication throughout. The primary endpoint was forced expiratory volume in 1 second (FEV₁) at 5 minutes post-dose. Secondary endpoints included proportion of patients achieving ≥12% increase in FEV₁ at 5 minutes post-dose.

RESULTS:

109 patients were randomized, and 108 completed the study. The increase in FEV₁ 5 minutes post-dose versus pre-dose was 7.2% for formoterol, 4.1% for salmeterol and 0.7% for placebo, and significantly greater for formoterol versus salmeterol (ratio of treatment effects: 1.030; 95% CI 1.008, 1.052; p = 0.009), for formoterol versus placebo (1.064, 95% CI 1.041, 1.087; p < 0.001) and for salmeterol versus placebo (1.033, 95% CI 1.011, 1.056; p = 0.003). The proportions of patients with ≥12% increase in FEV₁ 5 minutes post-dose were 23.1%, 9.2% and 6.4% for formoterol, salmeterol and placebo, respectively; this was statistically significantly larger after formoterol than salmeterol (p = 0.008) or placebo (p < 0.001). All treatments were well tolerated.

CONCLUSION:

In COPD patients, formoterol 9 μg has an onset of bronchodilatory effect that is more rapid than salmeterol 50 μg based on FEV₁ at 5 minutes post-dose.

CLINICAL TRIAL REGISTRATION:

Clinicaltrials.gov identifier: NCT01048333; AstraZeneca study code: D5127C00001.

• Authors: Mario Cazzola, Pierluigi Paggiaro, Paolo Palange, Leif Bjermer, Pilar Ausin, Lars-Goran Carlsson, Jan Ekelund, Jan Lotvall
• Journal: Clinical drug investigation (Clin Drug Investig) Vol. 32 Issue 3 Pg. 147-55 (Mar 01 2012) ISSN: 1179-1918 [Electronic] New Zealand
• PMID: 22235841 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Bronchodilator Agents
• Ethanolamines
• Salmeterol Xinafoate
• Albuterol
• Formoterol Fumarate

Topics

• Adult
• Aged
• Aged, 80 and over
• Albuterol (administration & dosage, analogs & derivatives)
• Bronchodilator Agents (administration & dosage)
• Cross-Over Studies
• Double-Blind Method
• Dry Powder Inhalers
• Ethanolamines (administration & dosage)
• Female
• Forced Expiratory Volume
• Formoterol Fumarate
• Humans
• Male
• Middle Aged
• Pulmonary Disease, Chronic Obstructive (drug therapy, physiopathology)
• Salmeterol Xinafoate