Pharmacokinetics (PK) and safety of budesonide plus formoterol (BF) (320/9mcg) Spiromax® and BF (400/12mcg) Turbuhaler® following two inhalations (+/- charcoal [char] block) in healthy volunteers (HV)

Objective: This was an open-label, single-dose, randomised, 5-way crossover study that evaluated the comparative PK and safety of BF (an inhaled corticosteroid/long-acting β 2 -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 320/9mcg –char, BF Turbuhaler 400/12mcg –char (repeated to evaluate intrasubject variability), BF Spiromax 320/9mcg +char and BF Turbuhaler 400/12mcg +char. The washout period was 7(±2) days. The primary endpoints were AUC 0-t (h*pg/mL) and C max (pg/mL) for B and F. Results: Eighty-seven HVs completed each treatment period. The 90% CIs of the geometric mean ratios for AUC 0-t and C max of B and F with BF Spiromax and BF Turbuhaler were bioequivalent (within range 0.8000–1.2500; with or without char). Nineteen treatment-emergent AEs were reported (3, BF Spiromax –char; 7, BF Turbuhaler –char; 5, BF Spiromax +char; 4, 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: PK effects of BF Spiromax were 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. EudraCT No: 2012-000485-37.