دورية أكاديمية
أعرض في EDS

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.

التفاصيل البيبلوغرافية
العنوان: 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.
المؤلفون: Krug AW; Merck & Co., Inc., Kenilworth, New Jersesy, USA., Vaddady P; Merck & Co., Inc., Kenilworth, New Jersesy, USA., Railkar RA; Merck & Co., Inc., Kenilworth, New Jersesy, USA., Musser BJ; Merck & Co., Inc., Kenilworth, New Jersesy, USA., Cote J; Merck & Co., Inc., Kenilworth, New Jersesy, USA., Ederveen A; CBG-MEB, Utrecht, The Netherlands., Krefetz DG; PRA Health Sciences, Marlton, New Jersey, USA., DeNoia E; ICON Development Solutions, San Antonio, Texas, USA., Free AL; Pinnacle Research Group, Anniston, Alabama, USA., Morrow L; Profil Institute for Clinical Research, Chula Vista, California, USA., Chakravarthy MV; Merck & Co., Inc., Kenilworth, New Jersesy, USA.; Eli Lilly & Co., Lilly Corporate Center, Indianapolis, IN 46285, USA., Kauh E; Merck & Co., Inc., Kenilworth, New Jersesy, USA., Tatosian DA; Merck & Co., Inc., Kenilworth, New Jersesy, USA., Kothare PA; Merck & Co., Inc., Kenilworth, New Jersesy, USA.
المصدر: Clinical and translational science [Clin Transl Sci] 2017 Sep; Vol. 10 (5), pp. 404-411. Date of Electronic Publication: 2017 Jul 20.
نوع المنشور: Clinical Trial, Phase I; Journal Article; Multicenter Study; Randomized Controlled Trial
اللغة: English
بيانات الدورية: Publisher: WileyBlackwell Pub Country of Publication: United States NLM ID: 101474067 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1752-8062 (Electronic) Linking ISSN: 17528054 NLM ISO Abbreviation: Clin Transl Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Malden, MA : WileyBlackwell Pub., 2008-
مواضيع طبية MeSH: Diabetes Mellitus, Type 2/*drug therapy , Receptors, G-Protein-Coupled/*antagonists & inhibitors, Adult ; Aged ; Blood Glucose/metabolism ; Diabetes Mellitus, Type 2/blood ; Dose-Response Relationship, Drug ; Endpoint Determination ; Humans ; Least-Squares Analysis ; Middle Aged ; Models, Biological ; Proof of Concept Study ; Receptors, G-Protein-Coupled/metabolism ; Treatment Outcome
مستخلص: 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.
(© 2017 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.)
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المشرفين على المادة: 0 (Blood Glucose)
0 (FFAR1 protein, human)
0 (Receptors, G-Protein-Coupled)
تواريخ الأحداث: Date Created: 20170721 Date Completed: 20180618 Latest Revision: 20181113
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC5593169
DOI: 10.1111/cts.12479
PMID: 28727908
قاعدة البيانات: MEDLINE
الوصف
تدمد:1752-8062
DOI:10.1111/cts.12479