Pharmacokinetics (PK) and safety of budesonide plus formoterol (BF) (160/4.5mcg) Spiromax® and BF (200/6mcg) Turbuhaler® following two inhalations (+/- charcoal [char] block) in healthy volunteers (HV)

Objective: This open-label, single-dose, randomised, 5-way crossover study evaluated the comparative PK and safety of BF (an inhaled corticosteroid/long-acting b2-agonist combination) administered as two inhalations via a dry powder inhaler (DPI) DuoResp (BF) Spiromax® and by Symbicort® (BF) Turbuhaler® DPI in HV. Methods: HVs were randomised to five treatments: BF Spiromax 160/4.5mcg -char, BF Turbuhaler 200/6mcg -char (repeated to evaluate intrasubject variability), BF Spiromax 160/4.5mcg +char and BF Turbuhaler 200/6mcg +char. The washout period was 7(±2) days. The primary endpoints were AUC0-t (h∗pg/mL), and Cmax (pg/mL) for B and F. Results: Eighty-six HVs completed each treatment period. The 90% CIs of the geometric mean ratios for AUC0-t and Cmax of B and F with BF Spiromax and BF Turbuhaler were bioequivalent (within range 0.8000-1.2500; with or without char). Ten treatment-emergent AEs were reported (3, BF Turbuhaler -char; 2, BF Spiromax +char; 5, BF Turbuhaler +char). All were mild-to-moderate in intensity with headache the most common. There were no clinically significant findings in vital signs, laboratory results or ECG. Conclusions: In this study BF Spiromax was bioequivalent to BF Turbuhaler for both B and F when administered with or without charcoal. Treatments were well tolerated and the safety profile between BF Spiromax and BF Turbuhaler was similar. These observations indicate that the two products should have comparable efficacy and safety.