Abediterol, a novel long-acting β2-agonist: bronchodilation, safety, tolerability and pharmacokinetic results from a single-dose, dose-ranging, active-comparator study in patients with COPD

Abstract

BackgroundAbediterol is a novel, once-daily long-acting β2-agonist in development for the treatment of chronic obstructive pulmonary disease (COPD) and asthma in combination with an anti-inflammatory agent. This Phase IIa, randomised, double-blind, crossover study investigated the bronchodilation, safety, tolerability and pharmacokinetics of abediterol in patients with moderate to severe COPD.MethodsSeventy patients (aged ≥40 years, Global initiative for chronic Obstructive Lung Disease Stage II/III) were randomised (1:1:1:1:1:1) to single doses of abediterol 0.625, 2.5, 5 or 10 μg, indacaterol 150 μg or placebo. Spirometry was performed up to 36 h post-dose. Pharmacokinetics were assessed in a subset of patients (N = 20). Safety and tolerability were evaluated throughout the study.ResultsAbediterol (all doses) significantly improved change from baseline in trough forced expiratory volume in 1 s (FEV1) compared with placebo (0.102, 0.203, 0.233 and 0.259 L for abediterol 0.625, 2.5, 5 and 10 μg, respectively; all p < 0.0001; primary endpoint). Abediterol 2.5, 5 and 10 μg significantly improved trough FEV1 compared with indacaterol 150 μg (0.092, 0.122 and 0.148 L, respectively; all p < 0.0001). Improvements in bronchodilation were maintained at all time points post-dose versus placebo (all abediterol doses) and from 15 or 30 min post-dose versus indacaterol 150 μg with abediterol 2.5, 5 and 10 μg (all p < 0.05). Abediterol had low systemic exposure; incidence of treatment-emergent adverse events was similar between treatment groups.ConclusionsAll doses of abediterol (0.625–10 μg) provided clinically and statistically significant, dose-dependent improvements in bronchodilation versus placebo, and abediterol 2.5, 5 and 10 μg gave significant improvements versus indacaterol. All doses of abediterol were safe and well tolerated in patients with COPD.Trial registrationClinicaltrials.gov NCT01425814. Registered 29 August 2011.

Efficacy, safety, and tolerability of once‐daily abediterol in patients with stable, persistent asthma: a Phase II, randomized, 7‐day, crossover study

“…Later dose-ranging studies of abediterol in patients with stable asthma (dose range 0.313-2.5 lg (Singh et al 2014)) and in patients with stable COPD (dose range 0.625-10 lg (Beier et al 2016) once daily) have demonstrated clinically and statistically significant dose-related improvements in bronchodilation compared with placebo. The lack of dose-response in bronchodilatory effect in this study suggests that the doses tested were at the top of the dose-response curve.…”

“…; Beier et al. ). In patients with mild‐to‐moderate asthma, abediterol (5–25 μ g) demonstrated significant improvements in lung function compared with placebo and salmeterol 50 μ g twice daily as early as 5 min postdose, with a safety and tolerability profile consistent with that expected for a β 2 ‐agonist (Beier et al.…”

“…Preclinical data show that abediterol is a potent, selective, and full b 2 -adrenoceptor agonist with a rapid onset of action and long-lasting effects (Aparici et al 2012). Early-phase clinical studies have shown that abediterol ≤10 lg is well tolerated with no clinically relevant effects on heart rate, blood glucose, or serum potassium in healthy subjects, patients with asthma, or patients with COPD (Singh et al 2014;Timmer et al 2014;Beier et al 2016). In patients with mild-to-moderate asthma, abediterol (5-25 lg) demonstrated significant improvements in lung function compared with placebo and salmeterol 50 lg twice daily as early as 5 min postdose, with a safety and tolerability profile consistent with that expected for a b 2 -agonist (Beier et al 2014).…”

Progress and Prospects for Long-Acting Β 2 -Agonists in the Treatment of Chronic Obstructive Pulmonary Disease

“…Все дозы абедитерола хорошо переносились. Также у 70 больных с ХОБЛ со стадиями GOLD 2-3 все дозы абедитерола (0,625-10 мкг) обеспечивали клинически и статистически значимую, зависимую от дозы бронходилатацию в сравнении с плацебо и хорошо переносились [51]. Интересно, что абедите-рол в дозах 2,5, 5 и 10 мкг приводил к достоверному улучшению по сравнению с индакатеролом.…”

Progress and Prospects for Long-Acting Β 2 -Agonists in the Treatment of Chronic Obstructive Pulmonary Disease (Copd)

“…All doses of abediterol were well tolerated. Also in 70 COPD patients who were GOLD stage 2/3, all doses of abediterol (0.625-10 μg) provided clinically and statistically significant, dose-dependent improvements in bronchodilation versus placebo, and were well tolerated [51]. Interestingly abediterol 2.5, 5 and 10 μg gave significant improvements versus indacaterol.…”