Pharmacokinetics of indacaterol acetate and mometasone furoate delivered alone or in a free or fixed dose combination in healthy volunteers

Purpose: QMF149 is a fixed-dose combination of the long-acting β2 agonist, indacaterol acetate and the corticosteroid, mometasone furoate that is currently under development for treatment of patients with asthma and chronic obstructive pulmonary disease. We describe here a study designed to assess any pharmacokinetic and/or biopharmaceutical interaction between indacaterol and mometasone furoate when administered via the Breezhaler® device, either alone or in a free or fixed combination (QMF149) in healthy adult volunteers. Methods: In this randomized, open-label, four-way crossover study, volunteers were randomised to receive indacaterol 150 µg, mometasone furoate 320 µg, alone and as free combination of the individual components, or QMF149 (indacaterol 150 μg /mometasone furoate 320 μg) once daily for 14 days in each period, followed by a 7-day washout between periods. Pharmacokinetic parameters were characterised on Day 14 up to 168 h post-dose. Results: Indacaterol AUC0-24h,ss and Cmax,ss after administration of QMF149 were 13% [ratio: 1.13; 90%CI: 1.09, 1.17] and 18% [ratio: 1.18; 90%CI: 1.12, 1.25] higher, respectively, than indacaterol monotherapy. Mometasone furoate AUC0-24h,ss and Cmax,ss after administration of QMF149 were 14% [ratio: 1.14; 90%CI: 1.09, 1.20] and 19% [ratio: 1.19; 90%CI: 1.13, 1.26], , higher, respectively than mometasone furoate monotherapy. The majority of the 90% confidence intervals of the between-treatment ratios for AUC0-24h,ss and Cmax,ss were within the 0.8 to 0.125 interval and therefore fulfilled bioequivalence criteria. The results of this study showed that there are no clinically meaningful changes in exposure between the treatment with the individual components and combination treatments. Multiple inhaled doses of indacaterol and mometasone furoate, when administered alone, in free combination or as QMF149 were well tolerated. Conclusions: The QMF149 fixed dose combination treatment showed comparable systemic exposure to the free combination and monotherapy treatments in terms of AUC0-24h,ss and Cmax,ss for both indacaterol and mometasone furoate, indicating a lack of clinically relevant PK or biopharmaceutical interaction. These data support further development of QMF149 without dose adjustment