Bioequivalence of budesonide plus formoterol (BF) Spiromax® and BF Turbohaler® (with and without charcoal block) in healthy volunteers.

Abstract Budesonide formoterol (BF) Spiromax® is a breath-actuated dry-powder inhaler designed to deliver similar combinations of budesonide and formoterol as Symbicort® Turbohaler®. We performed two studies to demonstrate pharmacokinetic (PK) equivalence of BF Spiromax with BF Turbohaler. Two single-center, open-label, randomized, 5-period crossover studies were performed. The first study compared BF Spiromax 160/4.5 μg with BF Turbohaler 200/6 μg, while the second study compared BF Spiromax 320/9 μg with BF Turbohaler 400/12 μg. All treatments were administered with and without charcoal. PK parameters were calculated by measuring plasma drug concentrations from blood samples taken pre-dose and up to 24 hours post-dose. In each study, 90 healthy volunteers were randomized. Bioequivalence of BF Spiromax with BF Turbohaler was demonstrated for budesonide and formoterol (AUC0-t and Cmax (90% confidence intervals of the geometric mean between-device ratios for both parameters were within the predefined range of 0.80-1.25 in both studies)). Equivalence was observed without use of charcoal (overall absorption post-inhalation) and with charcoal (pulmonary absorption). There were no major differences between treatments in tmax for either budesonide or formoterol. All study treatments were well tolerated (one treatment-emergent adverse event (TEAE) in the medium-dose study and four TEAEs in the high-dose study). These studies indicate that BF Spiromax (±charcoal block) is bioequivalent to BF Turbohaler with respect to the PK parameters assessed. Single doses of BF Spiromax were well tolerated; the overall safety profile of BF Spiromax and BF Turbohaler was similar.