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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.

Rhee SJ, Lee S, Yoon SH, Cho JY, Jang IJ, Yu KS - Drug Des Devel Ther (2016)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Schematic diagram of study design and dosing schedule.Abbreviations: FDC_EVO5/MET1000, fixed-dose combination formulation of evogliptin 5 mg and metformin XR 1,000 mg; EVO+MET, co-administration of the individual products of evogliptin 5 mg and metformin XR 1,000 mg; XR, extended-release.
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f1-dddt-10-1411: Schematic diagram of study design and dosing schedule.Abbreviations: FDC_EVO5/MET1000, fixed-dose combination formulation of evogliptin 5 mg and metformin XR 1,000 mg; EVO+MET, co-administration of the individual products of evogliptin 5 mg and metformin XR 1,000 mg; XR, extended-release.

Mentions: In Part 1, a total of 36 subjects were randomized to two treatment sequences, in which the treatments consisted of a single oral dose of FDC_EVO5/MET1000 or a co-administration of the individual products of evogliptin 5 mg and metformin XR 1,000 mg (EVO+MET): Sequence A, FDC_EVO5/MET1000 followed by EVO+MET; and Sequence B, EVO+MET followed by FDC_EVO5/MET1000 (Figure 1). Each study drug, according to the assigned sequence, was administered under fasting conditions along with 240 mL of water. Food was restricted from 10 hours pre-dose until 4 hours post-dose, and water was not permitted from 1 hour before dosing until 2 hours following dosing.


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.

Rhee SJ, Lee S, Yoon SH, Cho JY, Jang IJ, Yu KS - Drug Des Devel Ther (2016)

Schematic diagram of study design and dosing schedule.Abbreviations: FDC_EVO5/MET1000, fixed-dose combination formulation of evogliptin 5 mg and metformin XR 1,000 mg; EVO+MET, co-administration of the individual products of evogliptin 5 mg and metformin XR 1,000 mg; XR, extended-release.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4835124&req=5

f1-dddt-10-1411: Schematic diagram of study design and dosing schedule.Abbreviations: FDC_EVO5/MET1000, fixed-dose combination formulation of evogliptin 5 mg and metformin XR 1,000 mg; EVO+MET, co-administration of the individual products of evogliptin 5 mg and metformin XR 1,000 mg; XR, extended-release.
Mentions: In Part 1, a total of 36 subjects were randomized to two treatment sequences, in which the treatments consisted of a single oral dose of FDC_EVO5/MET1000 or a co-administration of the individual products of evogliptin 5 mg and metformin XR 1,000 mg (EVO+MET): Sequence A, FDC_EVO5/MET1000 followed by EVO+MET; and Sequence B, EVO+MET followed by FDC_EVO5/MET1000 (Figure 1). Each study drug, according to the assigned sequence, was administered under fasting conditions along with 240 mL of water. Food was restricted from 10 hours pre-dose until 4 hours post-dose, and water was not permitted from 1 hour before dosing until 2 hours following dosing.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus