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.
Clin Transl Sci
; 10(5): 404-411, 2017 Sep.
Article
em En
| MEDLINE
| ID: mdl-28727908
ABSTRACT
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 Tmax 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores Acoplados a Proteínas G
/
Diabetes Mellitus Tipo 2
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Adult
/
Aged
/
Humans
/
Middle aged
Idioma:
En
Revista:
Clin Transl Sci
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos