Pharmacokinetic Pilot Study on Budesonide/Formoterol Device-metered Dry Powder Inhalers

In order to reduce variability, a crossover design is chosen. An open study design is regarded appropriate because the study is a pilot and the primary study variables are pharmacokinetic(PK) parameters derived from drug concentrations in plasma. Wash-out period of at least 3 days between the study treatment administration days is considered sufficient for the elimination of budesonide and formoterol. The single dose study is suitable for this kind of study, where the aim is to compare products and the therapeutic response is not measured. The dose level selected is 2 inhalations (single dose) for all products. The administration of 2 inhalations enables the determination of budesonide and formoterol concentrations in plasma. In this study the investigational products are administered concomitantly with oral charcoal to block the GI absorption and to assess the pulmonary deposition of the active substances. Comparison of pulmonary deposition between the products is considered more relevant than systemic exposure at this point of product development. In the pivotal PK study total systemic exposure will also be assessed. Blood samples for formoterol analysis will be collected up to 24 hours and for budesonide analysis up to 12 hours after dosing to cover at least 80% of the total area under the concentration-time curve from time zero extrapolated to infinity (AUC∞).