Pharmacokinetics of the evogliptin/metformin extended-release (5/1,000 mg) fixed-dose combination formulation compared to the corresponding loose combination, and food effect in healthy subjects

• Published in: Drug design, development and therapy Vol. 10; no. Issue 1; pp. 1411 - 1418
• Main Authors: Yu, Kyung-Sang, Rhee, Su-jin, Lee, Seung Hwan, Yoon, Seo Hyun, Cho, Joo-Youn, Jang, In-Jin
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2016; Taylor & Francis Ltd; Dove Medical Press
• Subjects: Administration, Oral; Adult; Antidiabetics; Bioavailability; bioequivalence; Chemistry, Pharmaceutical; Clinical trials; Confidence intervals; Controlled release technology; Cross-Over Studies; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Dosage and administration; Dose-Response Relationship, Drug; Drug dosages; Drug therapy; Drug Therapy, Combination; Eating; evogliptin; Fasting; fixed-dose combination; Food; food effect; Healthy Volunteers; Humans; Hyperglycemia; Hypoglycemic agents; Innovations; Male; Metformin; Metformin - administration & dosage; Metformin - blood; Metformin - pharmacokinetics; metformin XR; Middle Aged; Original Research; Parameters; Patients; Pharmacokinetics; Pharmacology; Piperazines - administration & dosage; Piperazines - blood; Piperazines - pharmacokinetics; Product safety; Randomization; Structure-Activity Relationship; Type 2 diabetes; Young Adult; United States > US; pharmacokinetics; metformin XR; food effect; fixed-dose combination; bioequivalence; evogliptin
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S102459

A new fixed-dose combination formulation of evogliptin 5 mg and metformin extended-release (XR) 1,000 mg (FDC_EVO5/MET1000) was developed to improve medication adherence for type 2 diabetes mellitus. The pharmacokinetics of FDC_EVO5/MET1000 was compared to the corresponding loose combination in a randomized, open-label, crossover study in 36 healthy male subjects (Part 1), and the food effect on FDC_EVO5/MET1000 was assessed (under fasted or fed conditions) in a randomized, open-label, crossover study in 28 healthy male subjects (Part 2). Serial blood samples for pharmacokinetic analysis were collected up to 72 hours, and pharmacokinetic parameters of evogliptin and metformin were calculated using non-compartmental methods. The geometric mean ratios (fixed-dose combination to loose combination) and 90% confidence intervals of pharmacokinetic parameters for evogliptin and metformin were all within 0.800-1.250, suggesting bioequivalent pharmacokinetic. After a single oral dose of FDC_EVO5/MET1000, food did not significantly affect evogliptin pharmacokinetic while systemic exposure of metformin was increased about 47.5% under the fed condition, which is consistent with the already established food effect on metformin XR. FDC_EVO5/MET1000 was generally well tolerated without any drug-related serious adverse events. In conclusion, FDC_EVO5/MET1000 can be substituted for the loose combination of FDC_EVO5/MET1000, providing better compliance with convenient administration.