Effect of antistatic AeroChamber Plus® Flow-Vu® spacer on the systemic bioavailability of CHF5993 a novel triple pMDI

Abstract

Background: This study evaluated the effect of antistatic AeroChamber Plus® Flow-Vu® spacer on the systemic exposure to extrafine CHF5993 pMDI, a new fixed dose combination of Beclometasone Dipropionate (BDP), Formoterol Fumarate (FF), and Glycopyrronium Bromide (GB), being developed as a twice-daily treatment in COPD and asthma. Methods: Randomised, open-label, placebo-controlled, single dose, 3-way crossover study in moderate/severe COPD patients. They received 4 inhalations of CHF5993 pMDI (BDP/FF/GB total dose 400/24/100 µg) with or without spacer. Results: Thirty-five randomised patients completed the study. Compared with pMDI alone, the spacer increased GB Cmax and AUC0-30min by 60% and AUC0-t by 45%, reflecting higher lung deposition and the limited contribution of oral absorption to GB total systemic exposure. The spacer also increased B17MP and formoterol Cmax and AUC0-30min (by 20% for B17MP and by 55% for formoterol) and decreased AUC0-t by 37% and 24%, respectively, reflecting a higher lung deposition and prevention of oral absorption, counterbalancing increased lung absorption. The effect of the spacer was mainly observed in patients with inadequate inhalation technique due to poor coordination. CHF5993 pMDI showed a good and similar safety profile with and without spacer and in comparison with placebo. Conclusion: The observed changes in terms of total exposure and the observed safety profile support the use of the spacer with CHF5993 pMDI. These changes are not expected to have an impact on efficacy since as expected the spacer increases the lung deposition of all CHF5993 pMDI components.