Vaidya, Soniya, Khindri, Sanjeev, Maahs, Suzanne, Machineni, Surendra Kumar, Hara, Hisanori, Juan, Axel and Kaiser, Guenther (2016) Lung Delivery of Indacaterol and Mometasone Furoate Following Inhalation of QMF149 via the Twisthaler® Device in Healthy Volunteers. Clinical Pharmacology in Drug Development. ISSN 2160763X

Abstract

QMF149 is a once-daily fixed-dose combination of the long-acting β2-agonist indacaterol and the inhaled corticosteroid mometasone furoate (MF) under development for the treatment of asthma and chronic obstructive pulmonary disease. This study evaluated the contribution of pulmonary and gastrointestinal (GI) absorption to the systemic exposure of indacaterol and MF following inhalation of QMF149 via the Twisthaler® device.
This was an open-label, single-dose, four-period crossover study in 20 healthy subjects. Pharmacokinetics of indacaterol and MF were evaluated after inhalation of QMF149 (indacaterol maleate/MF) 500/400 μg via the Twisthaler® device with and without post-dose mouth rinsing, and in the presence of activated charcoal. Indacaterol alone was evaluated after inhalation of indacaterol maleate 300 μg via the Breezhaler® device.
The relative bioavailability of indacaterol and MF for inhalation with vs. without activated charcoal, based on AUClast, was 0.25 (90% confidence interval [CI]: 0.18, 0.35) and 0.70 (90% CI: 0.52, 0.93), respectively. Thus, 25% of systemic exposure of indacaterol and 70% of systemic exposure of MF after inhalation via the Twisthaler® device were due to lung absorption and 75% and 30%, respectively, were due to GI absorption. Total systemic exposure of indacaterol was higher (~1.5 fold) when administered without mouth rinsing, whereas no relevant effect of mouth rinsing was seen for MF. Dose normalized AUClast for indacaterol inhaled via the Breezhaler® device was 2.3-fold higher than that for QMF149 via the Twisthaler® device. All treatments had a good safety profile and were well tolerated.
Comparison with data from a similar charcoal block study of indacaterol inhaled via the Breezhaler® device showed that the Breezhaler® device was more efficient than the Twisthaler® device for lung delivery of indacaterol.

Item Type:	Article
Keywords:	QMF149, Breezhaler® device, Twisthaler® device, lung delivery, indacaterol, mometasone furoate
Date Deposited:	06 Apr 2016 23:45
Last Modified:	06 Apr 2016 23:45
URI:	https://oak.novartis.com/id/eprint/22785