1. Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Properties of the GPR40 Agonist TAK-875: Results From a Double-Blind, Placebo-Controlled Single Oral Dose Rising Study in Healthy Volunteers
- Author
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Himanshu Naik, Jingtao Wu, Tomoaki Higuchi, Nobuhito Dote, E Leifke, Prabhakar Viswanathan, and Majid Vakilynejad
- Subjects
Adult ,Blood Glucose ,Male ,Agonist ,Adolescent ,medicine.drug_class ,medicine.medical_treatment ,Pharmacology ,Hypoglycemia ,Placebo ,Receptors, G-Protein-Coupled ,Food-Drug Interactions ,Young Adult ,Double-Blind Method ,Pharmacokinetics ,Diabetes mellitus ,Insulin Secretion ,Humans ,Insulin ,Medicine ,Pharmacology (medical) ,Sulfones ,Benzofurans ,C-Peptide ,Dose-Response Relationship, Drug ,business.industry ,Middle Aged ,medicine.disease ,Dietary Fats ,Tolerability ,Area Under Curve ,Pharmacodynamics ,Female ,business ,Half-Life - Abstract
TAK-875 is a selective G-protein-coupled receptor 40 agonist in development for the treatment of type 2 diabetes mellitus. This randomized, double-blind, placebo-controlled study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-875 following administration of a single oral dose of TAK-875 (25-800 mg) in 60 healthy volunteers. TAK-875 was eliminated slowly with a mean terminal elimination t(1/2) of approximately 28.1 to 36.6 hours. Systemic exposure of TAK-875 did not exhibit dose-proportional increases across the dose range evaluated due to a greater than proportional increase in exposure at doses greater than 200 mg. A preliminary food effect assessment indicated that coadministration of TAK-875 with a high-fat meal decreased C(max) of TAK-875 by 40% and AUC by 17%. Clinical adverse experiences were generally mild and transient. No dose-dependent pattern was observed. In healthy volunteers, no glucose-lowering effect and no increase in insulin or c-peptide secretion were evident following administration of TAK-875; the frequency of plasma glucose concentrations
- Published
- 2012