Pharmacokinetics and Safety of Chiglitazar, a Peroxisome Proliferator-Activated Receptor Pan-Agonist, in Patients < 65 and ≥ 65 Years With Type 2 Diabetes

Clin Pharmacol Drug Dev. 2021 Jul;10(7):789-796. doi: 10.1002/cpdd.893. Epub 2020 Dec 20.

Abstract

The effect of age on the pharmacokinetics and safety of chiglitazar was evaluated in patients < 65 and ≥ 65 years with type 2 diabetes mellitus (T2DM). A total of 20 T2DM patients (<65 vs ≥65 years 1:1) completed the study. Patients received multiple doses of 48 mg chiglitazar once daily for 7 days consecutively. After the first dosing, chiglitazar maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC) in patients ≥ 65 years were similar to those observed in patients < 65 years, with the geometric mean ratio (GMR) for Cmax and AUC being 97.22% and 96.83%, respectively. No significant difference was observed in Cmax (GMR, 97.23%) in the steady state. Compared with the patients < 65 years, a slight increase (8%-13%) of AUC was observed in the patients ≥ 65 years after multiple doses. Chiglitazar was generally well tolerated following multiple doses in both age groups. In conclusion, there were no significant clinical influences on the pharmacokinetic properties and safety profiles of chiglitazar between patients with T2DM < 65 and ≥ 65 years, indicating that in the future it is not required to adjust the dosing regimen by age for T2DM patients ≥ 65 years.

Keywords: age effect; chiglitazar; pharmacokinetics; type 2 diabetes patients.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Area Under Curve
  • Carbazoles / administration & dosage*
  • Carbazoles / adverse effects
  • Carbazoles / pharmacokinetics
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / pharmacokinetics
  • Male
  • Middle Aged
  • Peroxisome Proliferator-Activated Receptors / agonists
  • Propionates / administration & dosage*
  • Propionates / adverse effects
  • Propionates / pharmacokinetics

Substances

  • Carbazoles
  • Hypoglycemic Agents
  • Peroxisome Proliferator-Activated Receptors
  • Propionates
  • chiglitazar