Double-blind, double-dummy, multinational, multicenter, parallel-group design clinical trial of clinical non-inferiority of formoterol 12 microg/unit dose in a b.i.d. regimen administered via an HFA-propellant-pMDI or a dry powder inhaler in a 12-week treatment period of moderate to severe stable persistent asthma in adult patients

Respiration. 2005:72 Suppl 1:20-7. doi: 10.1159/000083689.

Abstract

Background: Pressurized metered-dose inhalers (pMDIs) have traditionally used CFCs as propellants. However, the worldwide phase-out of CFCs has necessitated the development of new pMDIs that use alternative propellants. One such replacement is the hydrofluoroalkane HFA-134a.

Objectives: This study sought to establish the clinical non-inferiority of a new HFA-134a-containing pMDI to a conventional dry powder inhaler (DPI) in the administration of formoterol to adult patients with moderate-to-severe, stable persistent asthma. The secondary aim was to collect safety data in a multiple-dose long-term study.

Methods: During this multicenter, double-blind, parallel study, 500 patients were randomized to receive 12 microg of formoterol twice daily for 12 weeks via either an HFA pMDI or a DPI. If necessary, the dose could be increased to 24 microg twice daily. At baseline, all patients (aged 18-70 years) had an FEV1 40-80% of predicted and a documented positive response to the reversibility test.

Results: After 12 weeks' therapy, the adjusted mean morning PEFR was 343.69 l/min in the formoterol HFA pMDI group and 344.56 l/min in the formoterol DPI group. Because the lower limit of the 95% CI for the between-group difference (-11.64 l/min) was well within the non-inferiority margin (-20 l/min), the HFA device was deemed clinically non-inferior to the DPI device. This finding was confirmed when evening PEFR and FEV1 were assessed. Both formulations of formoterol were well tolerated during prolonged multiple dosing.

Conclusions: This study provides evidence that the new HFA-formulated formoterol pMDI has a similar efficacy and safety profile to the conventional formoterol DPI in the treatment of patients with moderate-to-severe asthma.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aerosol Propellants*
  • Aged
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Bronchodilator Agents / administration & dosage*
  • Bronchodilator Agents / adverse effects
  • Bronchodilator Agents / therapeutic use
  • Double-Blind Method
  • Drug Administration Schedule
  • Ethanolamines / administration & dosage*
  • Ethanolamines / adverse effects
  • Ethanolamines / therapeutic use
  • Female
  • Forced Expiratory Volume / drug effects
  • Formoterol Fumarate
  • Humans
  • Hydrocarbons, Fluorinated*
  • Male
  • Metered Dose Inhalers
  • Middle Aged
  • Nebulizers and Vaporizers
  • Peak Expiratory Flow Rate / drug effects
  • Powders
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Aerosol Propellants
  • Bronchodilator Agents
  • Ethanolamines
  • Hydrocarbons, Fluorinated
  • Powders
  • Formoterol Fumarate