z-logo
open-access-imgOpen Access
Leveraging a Clinical Phase Ib Proof‐of‐Concept Study for the GPR40 Agonist MK‐8666 in Patients With Type 2 Diabetes for Model‐Informed Phase II Dose Selection
Author(s) -
Krug AW,
Vaddady P,
Railkar RA,
Musser BJ,
Cote J,
Ederveen AGH,
Krefetz DG,
DeNoia E,
Free AL,
Morrow L,
Chakravarthy MV,
Kauh E,
Tatosian DA,
Kothare PA
Publication year - 2017
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/cts.12479
Subject(s) - placebo , pharmacokinetics , pharmacodynamics , agonist , dosing , medicine , pharmacology , type 2 diabetes , hypoglycemia , diabetes mellitus , adverse effect , free fatty acid receptor 1 , insulin , endocrinology , receptor , alternative medicine , pathology
GPR40 mediates free fatty acid–induced insulin secretion in beta cells. We investigated the safety, pharmacokinetics, and glucose response of MK‐8666, a partial GPR40 agonist, after once‐daily multiple dosing in type 2 diabetes patients. This double‐blind, multisite, parallel‐group study randomized 63 patients (placebo, n = 18; 50 mg, n = 9; 150 mg, n = 18; 500 mg, n = 18) for 14‐day treatment. The results showed no serious adverse effects or treatment‐related hypoglycemia. One patient (150‐mg group) showed mild‐to‐moderate transaminitis at the end of dosing. Median MK‐8666 T max was 2.0–2.5 h and mean apparent terminal half‐life was 22–32 h. On Day 15, MK‐8666 reduced fasting plasma glucose by 54.1 mg/dL (500 mg), 36.0 mg/dL (150 mg), and 30.8 mg/dL (50 mg) more than placebo, consistent with translational pharmacokinetic/pharmacodynamic model predictions. Maximal efficacy for longer‐term assessment is projected at 500 mg based on exposure–response analysis. In conclusion, MK‐8666 was generally well tolerated with robust glucose‐lowering efficacy.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.
Having issues? You can contact us here