Pharmacokinetics, pharmacodynamics, safety, and tolerability of JNJ-38431055, a novel GPR119 receptor agonist and potential antidiabetes agent, in healthy male subjects

Clin Pharmacol Ther. 2011 Nov;90(5):685-92. doi: 10.1038/clpt.2011.169. Epub 2011 Oct 5.


The incidence of type 2 diabetes mellitus is increasing worldwide. Several G-protein-coupled receptor agonists are being studied for their efficacy as antidiabetes agents. JNJ-38431055 is a novel, potent, and orally available selective agonist of the glucose-dependent insulinotropic (GPR119) receptor. Double-blind, randomized, placebo-controlled studies were conducted to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single oral doses of JNJ-38431055 (2.5-800 mg) in healthy male volunteers. The systemic exposure of JNJ-38431055 in plasma increased in proportion to the dose and was not influenced by coadministration of food. The terminal elimination half-life was ~13 h when administered as an oral suspension formulation. JNJ-38431055 was well tolerated and was not associated with hypoglycemia. As compared with placebo, single-dose oral JNJ-38431055 increased postmeal plasma glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and peptide YY (PYY) concentrations but did not significantly decrease glucose excursion or increase insulin secretion. However, in a graded glucose infusion study, JNJ-38431055 was shown to induce a higher insulin secretion rate (ISR) relative to placebo at elevated plasma glucose levels. These studies provide evidence for the potential efficacy of JNJ-38431055 as an antidiabetes agent in humans.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Blood Glucose / drug effects*
  • Double-Blind Method
  • Gastric Inhibitory Polypeptide / blood
  • Gastric Inhibitory Polypeptide / drug effects
  • Glucagon-Like Peptide 1 / blood
  • Glucagon-Like Peptide 1 / drug effects
  • Half-Life
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / pharmacokinetics
  • Hypoglycemic Agents / pharmacology*
  • Insulin / metabolism
  • Insulin Secretion
  • Male
  • Middle Aged
  • Peptide YY / blood
  • Peptide YY / drug effects
  • Receptors, G-Protein-Coupled / agonists*


  • Blood Glucose
  • GPR119 protein, human
  • Hypoglycemic Agents
  • Insulin
  • Receptors, G-Protein-Coupled
  • Peptide YY
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1