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An open‐label clinical trial of the effects of age and gender on the pharmacodynamics, pharmacokinetics and safety of the ghrelin receptor agonist anamorelin
Author(s) -
Leese Philip T.,
Trang John M.,
Blum Robert A.,
de Groot Eleanor
Publication year - 2015
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.175
Subject(s) - medicine , pharmacokinetics , pharmacodynamics , tolerability , agonist , cohort , cmax , area under the curve , cohort study , adverse effect , endocrinology , physiology , receptor
Purpose To assess the effect of age and gender on the pharmacokinetics (PK) of the ghrelin receptor agonist anamorelin. Methods Three demographic cohorts of healthy subjects were enrolled in this single‐center, open‐label study. Subjects received a single oral dose (25 mg) of anamorelin HCl. Serial blood samples were collected over 24 hours to assess anamorelin PK and circulating growth hormone (GH) levels. Data were compared with a reference cohort. Results Anamorelin was rapidly absorbed in all cohorts; peak concentrations were observed 30–45 minutes and 2–4 hours post‐dose, which declined biexponentially with mean terminal half‐lives of 6–7 hours. An age effect on C max and AUC ∞ was not apparent; however, mean AUC ∞ values were approximately 1.8–1.9‐fold higher in the female cohorts than in the reference male cohort. GH increase was rapid and virtually identical in both sexes, though attenuated in elderly subjects. No clinically significant safety or tolerability findings were observed. Conclusions While PK parameters do suggest higher exposure in females, this effect is considered to be modest given the variability of the 6–8 subjects per cohort. Moreover, no such effect was observed in the pharmacodynamic responses, thus, dose adjustment for age and gender is considered unnecessary.