Comparison of the effect of beclometasone/formoterol in asthma patients after methacholine-induced bronchoconstriction: A noninferiority study using metered dose vs. dry powder inhaler

Br J Clin Pharmacol. 2019 Apr;85(4):729-736. doi: 10.1111/bcp.13847. Epub 2019 Feb 3.

Abstract

Aims: To demonstrate the noninferiority of extrafine beclomethasone/formoterol fumarate (BDP/FF) dry powder inhaler (DPI) vs. extrafine BDP/FF pressurized metered dose inhaler (pMDI; Foster® 100/6 μg NEXThaler and pMDI, respectively) in the onset of reliever effect after methacholine induced bronchospasm in asthmatic patients, evaluated in terms of forced expiratory volume in 1 s (FEV1 ) at 5 min postdose. The DPI provides an alternative device option for patients who cannot use a pMDI properly during an acute asthma attack.

Methods: Sixty-five patients received one inhalation of BDP/FF DPI, BDP/FF pMDI or placebo after methacholine challenge, according to a double-blind, double-dummy, cross-over design. Lung function and Borg dyspnoea score were assessed up to 30 min postdose.

Results: FEV1 adjusted mean difference between BDP/FF DPI and BDP/FF pMDI at 5 min postdose was 2 ml (95% confidence interval: -0.060; 0.065). A similar result was observed at the other time points. Median time to 85% recovery in FEV1 was 8 min for BDP/FF DPI, 7.5 min for BDP/FF pMDI and 28 min for placebo (P = 0.554 DPI vs. pMDI). The Borg score improved after treatment with both BDP/FF DPI and pMDI and the effect was greater than after placebo. Median time to reach 50% recovery was 4.2 min for BDP/FF DPI, 4.0 min for BDP/FF pMDI and 10.0 min for placebo (P = 0.609 DPI vs. pMDI).

Conclusions: Extrafine Foster® NEXThaler, a flow-independent DPI, is comparable to extrafine Foster® pMDI when administered as reliever therapy after methacholine challenge, thus supporting the maintenance and reliever therapy approach also with Foster® NEXThaler.

Keywords: Clinical Trials; asthma; inhalation.

Publication types

  • Equivalence Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adult
  • Anti-Asthmatic Agents / administration & dosage*
  • Asthma / drug therapy*
  • Beclomethasone / administration & dosage*
  • Bronchoconstriction / drug effects
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Combinations
  • Dry Powder Inhalers
  • Female
  • Formoterol Fumarate / administration & dosage*
  • Humans
  • Male
  • Metered Dose Inhalers
  • Methacholine Chloride / administration & dosage
  • Middle Aged
  • Placebos / administration & dosage
  • Powders
  • Treatment Outcome

Substances

  • Anti-Asthmatic Agents
  • Drug Combinations
  • Placebos
  • Powders
  • Methacholine Chloride
  • Beclomethasone
  • Formoterol Fumarate