title: First-in-human study of the safety, tolerability, pharmacokinetics and pharmacodynamics of abediterol (LAS100977), a novel long-acting Β2 -agonist.
abstract: Here we report the results of a first-in-human study to evaluate the safety, tolerability pharmacokinetics, and pharmacodynamics of abediterol, a new β2 -adrenergic agonist. Forty-eight healthy males aged 18-45 years received abediterol doses of 5, 10, 25, or 50 µg, or placebo. Safety and tolerability assessments included adverse event reporting, pulse and blood pressure monitoring, 12-lead electrocardiograms, laboratory tests, and physical examination. Pharmacodynamic assessments included whole body plethysmography to determine the bronchodilatory effect by means of airway conductance and resistance. Blood and urine samples were obtained for pharmacokinetic analyses. Abediterol showed an overall good safety and tolerability profile in the dose range tested, consistent with the expected characteristics of a β2 -adrenergic agonist. A dose-dependent increase of systemic treatment-emergent adverse events was observed, the most frequent being palpitations, tremor, nausea, and asthenia; most were mild in intensity and resolved without the need for intervention. Improvements in airway conductance (increase) and resistance (decrease) were greater for all doses of abediterol tested compared with placebo at all time-points up to 36 hours. This first-in-human study suggests a potent, rapid, and sustained bronchodilatory effect of abediterol in healthy male subjects. Lower doses are currently under investigation in patients with asthma and in patients with COPD.
authors.affiliation: Clinical Research Services Mannheim GmbH, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Timmer
authors.forename: Eric
authors.initials: E
authors.lastname: Massana
authors.forename: Eulalia
authors.initials: E
authors.lastname: Jimenez
authors.forename: Beatriz
authors.initials: B
authors.lastname: Seoane
authors.forename: Gonzalo
authors.initials: G
authors.lastname: de Miquel
authors.forename: Sandrine
authors.initials: S
authors.lastname: Ruiz
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D000328:Adult; D001993:Bronchodilator Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D008297:Male; D015363:Quinolones / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D016037:Single-Blind Method
chemical_list: C576952:5-(2-((6-(2,2-difluoro-2-phenylethoxy)hexyl)amino)-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one; D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D015363:Quinolones
keywords: COPD; abediterol; asthma; healthy adults; long-acting β2-agonist