Double-blind, double-dummy, multinational, multicenter, parallel-group design clinical trial of clinical non-inferiority of formoterol 12 μg/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

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, doubleblind, parallel study, 500 patients were randomized to receive 12 mu g of formoterol twice daily for 12 weeks via either an HFA pMDI or a DPI. If necessary, the dose could be increased to 24 mu g 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. Copyright (C) 2005 S. Karger AG, Basel.