Therapeutic equivalence of budesonide/formoterol delivered via breath-actuated inhaler vs pMDI

Abstract

Rationale To assess equivalence of twice daily (bid) budesonide/formoterol (BUD/FM) 160/4.5 μg via breath-actuated metered-dose inhaler (BAI) versus pressurized metered-dose inhaler (pMDI). Methods This 12-week, double-blind, multicenter, parallel-group study, randomized adolescents and adults (aged ≥12 years) with asthma (and ≥3 months daily use of inhaled corticosteroids) to BUD/FM BAI 2 × 160/4.5 μg bid, BUD/FM pMDI 2 × 160/4.5 μg bid, or BUD pMDI 2 × 160 μg bid. Inclusion required prebronchodilator forced expiratory volume in one second (FEV1) ≥45 to ≤85% predicted, and reversibility of ≥12% in FEV (ages 12 to <18 years) or ≥12% and 200 mL (ages ≥18 years). Confirmation that 60-min postdose FEV response to BUD/FM pMDI was superior to BUD pMDI was required before equivalence testing. Therapeutic equivalence was shown by treatment effect ratio of BUD/FM BAI vs BUD/FM pMDI on 60-min postdose FEV and predose FEV within confidence intervals (CIs) of 80-125%. Results Mean age of 214 randomized patients was 42.7 years. BUD/FM pMDI was superior to BUD pMDI (60-min postdose FEV treatment effect ratio, 1.10; 95% CI, 1.06-1.14; p < 0.001). Treatment effect ratios for BUD/FM BAI versus pMDI for 60-min postdose FEV (1.01; 95% CI, 0.97-1.05) and predose FEV (1.03; 95% CI, 0.99-1.08) were within predetermined CIs for therapeutic equivalence. Adverse event profiles, tolerability, and patient-reported ease of use were similar. Conclusions BUD/FM 2 × 160/4.5 μg bid BAI is therapeutically equivalent to BUD/FM conventional pMDI. The introduction of BUD/FM BAI would expand options for delivering inhaled corticosteroid/long-acting β-agonist combination therapy to patients with moderate-to-severe asthma. ClinicalTrials.gov NCT01360021.