Pharmacokinetics (PK) of single doses of mometasone furoate (MF) delivered via the Breezhaler® (BH) and Twisthaler® (TH) devices in healthy subjects

Background: QMF149 is being developed as a fixed dose combination of the long-acting β 2 -agonist indacaterol and the inhaled corticosteroid MF for treatment of asthma and COPD. Indacaterol is approved in the single dose dry power inhaler (DPI), BH for treatment of COPD (Onbrez® Breezhaler®). MF is approved in the multiple-dose DPI, TH for treatment of asthma (Asmanex® Twisthaler®). Due to its low oral bioavailability, systemic exposure after inhalation of MF reflects the amount of drug delivered to and absorbed from the lung. Objective: To evaluate the PK of single doses of MF administered by oral inhalation via BH and to compare the systemic exposure to MF delivered via BH and TH devices. Methods: This open-label, single-dose, crossover study recruited 24 healthy subjects to sequentially receive MF TH (400µg) and escalating doses of MF BH (50, 100, 200, 400µg). PK data were obtained up to 72h post-dose. Results: Twenty subjects completed all treatments. Dose-normalized AUC last for MF was 1.8 to 1.9-fold higher when delivered via BH compared to TH. AUC and C max of MF increased in a dose proportional manner over the dose range 50-400µg for MF BH. Median T max was reached earlier for all doses of MF BH (0.375-2 h) compared to MF TH 400µg (3h). The terminal half-life was similar for all treatments (mean T 1/2 :12-13h). Conclusion: Systemic exposure of MF increased in a dose proportional manner over the dose range 50-400µg for the MF BH. The estimated average dose of MF BH expected to provide systemic exposure comparable to the approved MF TH dose of 400µg was 195µg [(90% CI: (175, 215)].