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

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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 µg of formoterol twice daily for 12 weeks via either an HFA pMDI or a DPI. If necessary, the dose could be increased to 24 µg 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.