Relative pulmonary bioavailability (BA) of fluticasone propionate/formoterol (FP/FORM) via pressurised metered-dose inhaler (pMDI) and a novel breath-triggered inhaler (BTI)

Background: This study aimed to show that pulmonary BA of FP and FORM via the BTI (Flutiform® K‑haler®) was no less than via pMDI without a spacer, to establish a bridge from the efficacy of the pMDI to the BTI (EudraCT: 2012-003728-19). Methods: Single-dose, randomised, open-label, 3 treatment, 3 period, cross-over study in healthy adults. Treatments were FP/FORM 125/5µg, 2 puffs via BTI, pMDI or pMDI with spacer (pMDI+S). To measure pulmonary BA only, all subjects ingested charcoal suspension pre-dose and at 15min and 1h post-dose. The primary objective was to compare relative BA of FP and FORM via BTI and pMDI (secondary objectives included BTI vs pMDI+S). Acceptable pulmonary BA was concluded if the lower limit of the confidence intervals (CIs) of the BAI/pMDI ratios were ≥80%. Blood samples were taken pre-dose and for 36h post-dose. Results: Of 47 subjects randomised, 45 (95.7%) completed. The AUCt and Cmax ratios of BTI:pMDI for both FP and FORM analytes were between 107-131%. As the lower limits of the CIs of all BTI:pMDI ratios were >80% the study goal was met (Table). Conclusion: Pulmonary BA of FP/FORM via BTI was no less than via pMDI without spacer, indicating that the Flutiform K-haler product would be at least as effective as pMDI. Sponsor: Mundipharma Research Ltd Table. BA comparisons