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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.

ABSTRACT: To assess the effect of age and gender on the pharmacokinetics (PK) of the ghrelin receptor agonist anamorelin.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.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 Cmax 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.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.

SUBMITTER: Leese PT

PROVIDER: S-EPMC4657463 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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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.

Leese Philip T PT Trang John M JM Blum Robert A RA de Groot Eleanor E

Clinical pharmacology in drug development 20150209 2

<h4>Purpose</h4>To assess the effect of age and gender on the pharmacokinetics (PK) of the ghrelin receptor agonist anamorelin.<h4>Methods</h4>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.<h4>Results</h4>Anamorelin was ...[more]

PMID: 26640742

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Project description:INTRODUCTION:The B cell survival factor B lymphocyte stimulator (BLyS) is elevated in patients with systemic lupus erythematosus (SLE) and associated with disease activity. Belimumab, a monoclonal antibody specific for soluble BLyS, is approved for the treatment of adults with active, autoantibody-positive SLE receiving standard therapy. Ethnicity is one of the factors that can potentially affect the pharmacokinetics (PK) of therapeutic monoclonal antibodies, and therefore their efficacy and safety. METHODS:This phase 1, open-label study (200909) evaluated the pharmacokinetics (PK, primary objective), pharmacodynamics (PD), and safety (secondary objectives) of belimumab in Chinese patients with SLE (N = 20). Blood samples were taken up to 84 days after a single intravenous (IV) dose of belimumab 10 mg/kg. RESULTS:Peak serum concentrations of belimumab (Cmax) were obtained within the 1-h infusion. Geometric mean Cmax, area under the concentration-time curve (time 0 to last quantifiable concentration), terminal half-life, systemic clearance, and volume of distribution were 221 μg/mL, 2395 day·μg/mL, 14.6 days, 4.06 mL/day/kg, and 85.7 mL/kg, respectively. Decreases in CD20+, CD20+/CD27- naïve, CD20+/CD69+ active, CD20+/CD138+ plasmacytoid, CD19+/CD27BRIGHT/CD38BRIGHT SLE subset, and CD20-/CD138+ plasma B Cells post-dose were accompanied by an increase in CD20+/CD27+ memory B cells. Four cases of upper respiratory tract infection (three mild, one moderate) and one case of mild pharyngitis were possibly drug-related; all resolved during the study. CONCLUSION:PK of a single belimumab 10 mg/kg IV dose in Chinese patients with SLE were similar to those observed previously in Japanese and American (white and African-American) patients with SLE. PD results were consistent with belimumab inhibiting BLyS, and belimumab was well tolerated. These data support the use of belimumab in Chinese patients with SLE. TRIAL REGISTRATION:ClinicalTrials.gov identifier, NCT02880852.

Dataset Information

An open-label clinical trial of the effects of age and gender on the pharmacodynamics, pharmacokinetics and safety of the ghrelin receptor agonist anamorelin.

Publications

An open-label clinical trial of the effects of age and gender on the pharmacodynamics, pharmacokinetics and safety of the ghrelin receptor agonist anamorelin.

Similar Datasets

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