OBJECTIVE:Aclidinium bromide is a novel antimuscarinic being developed for the treatment of chronic obstructive pulmonary disease. The objective of this Phase I study was to determine the maximum tolerated dose (MTD) as well as the tolerability, safety and pharmacokinetics of aclidinium in healthy subjects. MATERIALS AND METHODS:16 healthy subjects were randomized to receive 5 single ascending doses of aclidinium 600 - 6,000 microg or placebo inhaled via dry powder inhaler, with 7 day washouts. Safety measurements included adverse events (AEs), physical examination, vital signs, pupillometry examination, clinical laboratory tests, and 12-lead electrocardiogram. Pharmacokinetic parameters of aclidinium and its metabolites were assessed. RESULTS: The incidence of AEs was comparable between aclidinium and placebo at all doses. Most AEs were mild to moderate with no dose-related or anticholinergic/cardiac AEs. At doses >or= 2,400 microg, only 13 AEs were considered treatment related. Aclidinium (600 - 6,000 microg) did not produce function-limiting or severe AEs in >or= 50% of subjects; hence, the prospectively-defined MTD was not established. Aclidinium was rapidly converted in plasma into alcohol and carboxylic acid metabolites, and was no longer detectable after 3 hours post-dose for all doses. At lower doses, aclidinium was quantifiable only up to 1 hour post-dose in the majority of subjects. Maximum plasma concentrations for aclidinium were reached within 5 - 7 minutes (all doses) and declined rapidly. Mean elimination half-lives of aclidinium > 2,400 microg were approximately 1 hour. AUC and Cmax increased proportionately up to 4,800 microg. CONCLUSIONS:Aclidinium appears to be safe and well tolerated in single doses of 600 - 6,000 microg.
RCT Entities:
OBJECTIVE:Aclidinium bromide is a novel antimuscarinic being developed for the treatment of chronic obstructive pulmonary disease. The objective of this Phase I study was to determine the maximum tolerated dose (MTD) as well as the tolerability, safety and pharmacokinetics of aclidinium in healthy subjects. MATERIALS AND METHODS: 16 healthy subjects were randomized to receive 5 single ascending doses of aclidinium 600 - 6,000 microg or placebo inhaled via dry powder inhaler, with 7 day washouts. Safety measurements included adverse events (AEs), physical examination, vital signs, pupillometry examination, clinical laboratory tests, and 12-lead electrocardiogram. Pharmacokinetic parameters of aclidinium and its metabolites were assessed. RESULTS: The incidence of AEs was comparable between aclidinium and placebo at all doses. Most AEs were mild to moderate with no dose-related or anticholinergic/cardiac AEs. At doses >or= 2,400 microg, only 13 AEs were considered treatment related. Aclidinium (600 - 6,000 microg) did not produce function-limiting or severe AEs in >or= 50% of subjects; hence, the prospectively-defined MTD was not established. Aclidinium was rapidly converted in plasma into alcohol and carboxylic acid metabolites, and was no longer detectable after 3 hours post-dose for all doses. At lower doses, aclidinium was quantifiable only up to 1 hour post-dose in the majority of subjects. Maximum plasma concentrations for aclidinium were reached within 5 - 7 minutes (all doses) and declined rapidly. Mean elimination half-lives of aclidinium > 2,400 microg were approximately 1 hour. AUC and Cmax increased proportionately up to 4,800 microg. CONCLUSIONS:Aclidinium appears to be safe and well tolerated in single doses of 600 - 6,000 microg.
Authors: Paul W Jones; Stephen I Rennard; Alvar Agusti; Pascal Chanez; Helgo Magnussen; Leonardo Fabbri; James F Donohue; Eric D Bateman; Nicholas J Gross; Rosa Lamarca; Cynthia Caracta; Esther Garcia Gil Journal: Respir Res Date: 2011-04-26
Authors: Dave Singh; Paul W Jones; Eric D Bateman; Stephanie Korn; Cristina Serra; Eduard Molins; Cynthia Caracta; Esther Garcia Gil; Anne Leselbaum Journal: BMC Pulm Med Date: 2014-11-18 Impact factor: 3.317