Pharmacometric Approaches to Guide Dose Selection of the Novel GPR40 Agonist TAK-875 in Subjects With Type 2 Diabetes Mellitus.

ABSTRACT: The G-protein-coupled receptor 40 agonist (GPR40) TAK-875 is being developed as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus. Pharmacometric approaches such as model-based exposure-response and meta-analyses were applied to (i) characterize exposure/dose-efficacy responses of TAK-875, (ii) characterize the time course of glycosylated hemoglobin A1c (HbA1c) response with TAK-875 6.25 to 200 mg q.d. doses for 12 weeks, (iii) project and compare HbA1c response with dipeptidyl peptidase 4 (DPP-4) inhibitors and TAK-875 up to 24 weeks, and (iv) provide a quantitative rationale for dose selection in phase 3. On the basis of phase 2 data, relationships between TAK-875 concentrations and HbA1c were well characterized by exposure-response mod

SUBMITTER: Naik H 

PROVIDER: S-EPMC3600727 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature