RT Journal Article
SR Electronic
T1 Pharmacokinetic interaction of glycopyrronium bromide pMDI and formoterol pMDI: A randomized, open-label, single-dose, 4-way cross-over study
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP PA2961
DO 10.1183/13993003.congress-2015.PA2961
VO 46
IS suppl 59
A1 Fabrizia Mariotti
A1 Sara Collarini
A1 Anna Compagnoni
A1 Dario Cuomo
A1 Annamaria Muraro
A1 Daniela Acerbi
YR 2015
UL http://erj.ersjournals.com/content/46/suppl_59/PA2961.abstract
AB Background: As part of the development program for an inhaled triple combination (CHF 5993 pMDI) as a twice-daily therapy for the treatment of COPD and asthma, with extrafine inhaled corticosteroid, Glycopyrronium bromide (GB), and Formoterol Fumarate (FF), this study investigated the pharmacokinetic (PK) interaction between GB and formoterol, the bronchodilator components of the combination.Methods: This was a randomized, open-label, placebo controlled, single-dose, 4-way cross-over study in healthy volunteers. They received a single dose of GB (total dose 100 μg) and FF (total dose 24 μg, Atimos®) as free combination (Test) or as single components (References).Results: 44 subjects, mean age (range) 42.3 years (20-65), 39% males, were randomised.GB had no impact on Formoterol exposure since the 90% CI of the geometric mean ratio for Formoterol Cmax and AUCt were within the equivalence interval of 80-125%.Similarly, the 90% CI for GB AUCt was within the pre-defined range. Higher maximum GB exposure (Cmax P.E. 119%, 90% CI 105%-134%) was observed after administration of the free combination in comparison with GB alone. However the higher exposure to GB immediately after inhalation was transient as indicated by the AUC0-30min confidence intervals which were within the 80-125% equivalence limits. In addition comparable cardiovascular profiles between treatments were observed.Conclusion: Study results supported the absence of clinically relevant pharmacokinetic interactions between extrafine GB and FF. The administered treatments were safe and well tolerated.