Pharmacokinetics (PK), safety and tolerability of abediterol and mometasone furoate fixed- and free-dose combinations in healthy subjects

Background Abediterol (LAS100977) is a novel, once-daily, LABA in development for the treatment of asthma and COPD. We investigated the PK and pharmaceutical interaction of mometasone furoate (inhaled corticosteroid) in combination with abediterol in healthy subjects. Methods In this Phase I, 4-way crossover study, healthy subjects were randomised to single doses of: fixed-dose combination (FDC) abediterol/mometasone 0.625/340 µg and 2.5/340 µg; free-dose combination abediterol+mometasone 2.5/340 µg; or mometasone 340 µg alone, via Genuair®/Pressair™, with ≥10-days washout. Endpoints included 36-hour PK parameters and safety and tolerability. Results 24/28 subjects completed the study (N=22 male, mean age 33.0 years [SD±7.0]). Mometasone disposition kinetics were similar across all treatments; tmax: 1.7 – 2.3 hours; t½: 8.5 – 9.4 hours. Abediterol tmax was achieved within 30 minutes (all treatments). Estimated t½ for abediterol 2.5 µg: 23.8 hours (FDC); 24.3 hours (free-dose). See table for PK parameter comparisons. All treatments were safe and well tolerated; the most common treatment-emergent adverse events were headache (14%), myalgia (11%), diarrhoea, nausea, vomiting and anxiety (each 7%). Conclusion Abediterol and mometasone co-administration (FDC or free-dose) has minimal impact on PK parameters of either drug within predicted therapeutic dose ranges. ![Figure][1] [1]: pending:yes