Pharmacodynamics (PD) of low and high strength budesonide plus formoterol (BF) Spiromax® and BF Turbuhaler® in healthy volunteers (HV)

Objective: To evaluate the PD effects of BF (inhaled corticosteroid/long-acting β 2 -agonist combination) administered as cumulative delivered doses (1+1+2+4 inhalations) by a dry powder inhaler(DPI) DuoResp (BF) Spiromax® and by Symbicort® (BF) Turbuhaler® DPI in HV. Methods: This was a single centre, double-blind, double-dummy, cumulative dose, 4-period crossover study. HVs were randomised to one of four treatment sequences containing: BF Spiromax 80/4.5mcg + placebo (P) Turbuhaler (+cuml F:36mcg), BF Turbuhaler 100/6mcg + P Spiromax (+cuml F:48mcg), BF Spiromax 320/9mcg + P Turbuhaler (+cuml F:72mcg) and BF Turbuhaler 400/12mcg + P Spiromax (+cuml F:96mcg). Primary endpoint was mean change from baseline (BL) in corrected QTcF interval at 5min after each of the four cumulative F doses. Secondary endpoints included change from baseline in QTcB, treatment-emergent adverse events (TEAE), vital signsand lab outputs. Results: The 90% CIs for the difference in change from BL in QTcF for both low and high strength BF at 5min were within equivalence bounds (±10msec) (low diff. −0.631 to 2.031; high diff. −3.448 to 0.285). Similar results were observed at 15min for QTcF and at 5 and 15min for QTcB. Each treatment period was completed by 52/56 HVs. Seventy-six TEAEs were reported by 27 HVs (most mild in intensity; most common was tremor) with no serious TEAEs. No clinically significant changes in lab outputs or vital signswere reported. Conclusions: PD effects of BF Spiromax and BF Turbuhaler at corresponding strengths were bioequivalentin this study. Both treatments were well tolerated and the safety profile between them similar. EudraCT No. 2010-021655-64.