Evaluation of the pharmacokinetic interaction between the dipeptidyl peptidase IV inhibitor LC15-0444 and pioglitazone in healthy volunteers

Int J Clin Pharmacol Ther. 2012 Jan;50(1):17-23. doi: 10.5414/cp201568.


Objective: LC15-0444, a newly developed selective dipeptidyl peptidase IV inhibitor, has the potential to be administered with other antihyperglycemic agents. The aim of this study was to investigate the interaction between LC15-0444 and pioglitazone by comparing the pharmacokinetics of both compounds and their metabolites.

Methods: A randomized, open-label, multiple dosing, three-sequence, three-period, three-treatment crossover study was performed in healthy volunteers. The three treatment groups were comprised of LC15-0444 200 mg, pioglitazone 30 mg, or coadministration of both drugs once daily for 12 days. Blood samples were collected up to 48 hours after the last dosing. Safety and tolerability were assessed throughout the study.

Results: The geometric mean ratios (GMRs; (LC15-0444+Pioglitazone coadministered)/(LC15-0444 or Pioglitazone alone)) (90% confidence intervals (CIs)) for Cmax,ss and AUCt,ss of LC15-0444 were 1.06 (0.96-1.16) and 0.98 (0.93-1.03), respectively. In the case of pioglitazone, the GMRs (90% CIs) for Cmax,ss and AUCt,ss were 0.84 (0.73-0.96) and 0.85 (0.76-0.96), respectively. All reported adverse events were mild in intensity.

Conclusions: The pharmacokinetics of LC15-0444 and its metabolites were not altered by pioglitazone. The systemic exposure of pioglitazone was decreased by 15% after coadministration of LC15-0444 with pioglitazone, but this was not judged to be clinically relevant, considering the total active moiety of pioglitazone.

Trial registration: ClinicalTrials.gov NCT01001013.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Area Under Curve
  • Cross-Over Studies
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacokinetics*
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology
  • Drug Interactions
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / pharmacokinetics*
  • Hypoglycemic Agents / pharmacology
  • Male
  • Middle Aged
  • Organic Chemicals / adverse effects
  • Organic Chemicals / pharmacokinetics*
  • Organic Chemicals / pharmacology
  • Pioglitazone
  • Piperidones
  • Pyrimidines
  • Thiazolidinediones / adverse effects
  • Thiazolidinediones / pharmacokinetics*
  • Thiazolidinediones / pharmacology
  • Young Adult


  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • LC15-0444
  • Organic Chemicals
  • Piperidones
  • Pyrimidines
  • Thiazolidinediones
  • Pioglitazone

Associated data

  • ClinicalTrials.gov/NCT01001013