Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of JNJ-38431055, a Novel GPR119 Receptor Agonist and Potential Antidiabetes Agent, in Healthy Male Subjects

• DOI: 10.1038/clpt.2011.169
• Publication Date: 2011-10-05T15:03:58Z
• Authors: L B Katz; J J Gambale; P L Rothenberg; S R Vanapalli; N Vaccaro; L Xi; D C Polidori; E Vets; T C Sarich; P P Stein
• Keywords: Pharmacodynamics; Tolerability

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 a novel, potent, and orally available selective agonist the glucose–dependent insulinotropic (GPR119) receptor. Double–blind, randomized, placebo–controlled studies were conducted to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics single oral doses (2.5–800 mg) in healthy male volunteers. systemic exposure plasma increased proportion dose was not influenced by coadministration food. terminal elimination half–life ~13 h when administered an suspension formulation. well tolerated associated with hypoglycemia. As compared placebo, single–dose postmeal glucagon–like peptide 1 (GLP–1), (GIP), YY (PYY) concentrations but did significantly decrease glucose excursion or increase insulin secretion. However, graded infusion study, shown induce higher secretion rate (ISR) relative placebo at elevated levels. These provide evidence potential agent humans. Clinical Pharmacology & Therapeutics (2011); 90 5, 685–692. doi:10.1038/clpt.2011.169