Population Pharmacokinetic Analyses of Ertugliflozin in Select Ethnic Populations

Clin Pharmacol Drug Dev. 2021 Nov;10(11):1297-1306. doi: 10.1002/cpdd.970. Epub 2021 Jul 2.

Abstract

Ertugliflozin, a sodium-glucose cotransporter 2 inhibitor, is approved for treatment of type 2 diabetes. Two population pharmacokinetic (PK) analyses were conducted, using data from up to 17 phase 1 to 3 studies, to characterize ertugliflozin PK parameters in select ethnic subgroups: (1) East/Southeast (E/SE) Asian vs non-E/SE Asian subjects; (2) Asian subjects from mainland China vs Asian subjects from the rest of the world and non-Asian subjects. A 2-compartment model with first-order absorption, lag time, and first-order elimination was fitted to the observed data. For the E/SE Asian vs non-E/SE Asian analysis (13 692 PK observations from 2276 subjects), E/SE Asian subjects exhibited a 17% increase in apparent clearance (CL/F) and 148% increase in apparent central volume of distribution (Vc/F) vs non-E/SE Asian subjects. However, individual post hoc CL/F values were similar between groups when body weight differences were considered. For the second analysis (16 018 PK observations from 2620 subjects), compared with non-Asian subjects, CL/F was similar while Vc/F increased by 44% in Asian subjects from mainland China and both CL/F and Vc/F increased in Asian subjects from the rest of the world (8% and 115%, respectively) vs non-Asian subjects. Increases in Vc/F would decrease the ertugliflozin maximum concentration but would not impact area under the concentration-time curve. Therefore, the differences in CL/F (area under the concentration-time curve) and Vc/F were not considered clinically relevant or likely to result in meaningful ethnic differences in the PK of ertugliflozin.

Trial registration: ClinicalTrials.gov NCT00989079 NCT01127308 NCT01054300 NCT01223339 NCT01948986 NCT01096667 NCT01059825 NCT01986855 NCT02033889 NCT02099110 NCT01958671 NCT02630706.

Keywords: diabetes; ertugliflozin; population pharmacokinetics; sodium-glucose cotransporter 2 inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Asia, Southeastern
  • Asians*
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacokinetics*
  • China
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Ethnicity
  • Far East
  • Female
  • Humans
  • Male
  • Middle Aged
  • Sodium-Glucose Transporter 2 Inhibitors / pharmacokinetics*

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Sodium-Glucose Transporter 2 Inhibitors
  • ertugliflozin

Associated data

  • ClinicalTrials.gov/NCT00989079
  • ClinicalTrials.gov/NCT01127308
  • ClinicalTrials.gov/NCT01054300
  • ClinicalTrials.gov/NCT01223339
  • ClinicalTrials.gov/NCT01948986
  • ClinicalTrials.gov/NCT01096667
  • ClinicalTrials.gov/NCT01059825
  • ClinicalTrials.gov/NCT01986855
  • ClinicalTrials.gov/NCT02033889
  • ClinicalTrials.gov/NCT02099110
  • ClinicalTrials.gov/NCT01958671
  • ClinicalTrials.gov/NCT02630706