Dataset Information

A Fixed-Dose Combination Of Gemigliptin And Rosuvastatin Exhibits Similar Pharmacokinetics, Pharmacodynamics, And Safety Compared To That Of A Loose Combination In Healthy Subjects.

ABSTRACT: Purpose:Fixed-dose combination (FDC) of gemigliptin and rosuvastatin may improve medication compliance of patients with comorbid type 2 diabetes and dyslipidemia. Pharmacokinetics (PK), pharmacodynamics (PD), and safety of gemigliptin/rosuvastatin 50/20 mg FDC was compared with a loose combination of individual tablets in healthy subjects. Patients and methods:A randomized, open-label, single-dose, two-period, two-sequence, two-treatment crossover study was conducted. Subjects received FDC or a loose combination of gemigliptin (50 mg) and rosuvastatin (20 mg) during each period, with a 14-day washout. Serial blood samples were collected up to 72 hrs after dosing to measure plasma concentrations of gemigliptin, its active metabolite LC15-0636, and rosuvastatin for PK assessment, and DPP-4 activity for PD assessment. PK and PD parameters were calculated using a non-compartmental method. Safety profiles were evaluated throughout the study. Results:Thirty-seven subjects completed the study. The concentration-time profiles of gemigliptin, LC15-0636, and rosuvastatin were similar between FDC and loose combination, respectively. For each of the three compounds, the geometric mean ratios (90% confidence interval) of FDC to loose combination for Cmax and AUClast fell within the bioequivalence range of 0.8-1.25. Inhibition of DPP-4 activity-time profiles after administration of FDC and loose combination was overlapping, and Imax and AUEClast were similar. Both FDC and the loose combination were well tolerated. Conclusion:PK, PD, and safety profiles of gemigliptin, its metabolite, and rosuvastatin were similar between FDC and loose combination. The FDC of gemigliptin (50 mg) and rosuvastatin (20 mg) can be used as an alternative to a loose combination, which is expected to improve patient compliance.

SUBMITTER: Kim E

PROVIDER: S-EPMC6859084 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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A Fixed-Dose Combination Of Gemigliptin And Rosuvastatin Exhibits Similar Pharmacokinetics, Pharmacodynamics, And Safety Compared To That Of A Loose Combination In Healthy Subjects.

Kim Eunwoo E Park Kyoung Ryun KR Jang In-Jin IJ Yu Kyung-Sang KS Lee SeungHwan S

Drug design, development and therapy 20191113

<h4>Purpose</h4>Fixed-dose combination (FDC) of gemigliptin and rosuvastatin may improve medication compliance of patients with comorbid type 2 diabetes and dyslipidemia. Pharmacokinetics (PK), pharmacodynamics (PD), and safety of gemigliptin/rosuvastatin 50/20 mg FDC was compared with a loose combination of individual tablets in healthy subjects.<h4>Patients and methods</h4>A randomized, open-label, single-dose, two-period, two-sequence, two-treatment crossover study was conducted. Subjects rec ...[more]

PMID: 32009778

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Project description:Background:A fixed-dose combination (FDC) tablet formulation of amlodipine/losartan/rosuvastatin 5/100/20 mg was developed to improve medication compliance in patients with both hypertension and dyslipidemia. The comparative pharmacokinetic study was performed to compare the profile of an FDC tablet formulation of amlodipine/losartan/rosuvastatin with that of concomitant administration of a currently marketed FDC tablet of amlodipine/losartan with a rosuvastatin tablet. Subjects and Methods:A randomized, open-label, single oral dose, two-way crossover study was conducted in 60 healthy subjects. Subjects were orally administered the FDC tablet of amlodipine/losartan/rosuvastatin and a loose combination (LC) of two tablets comprising an FDC of amlodipine/losartan and rosuvastatin. Blood samples were collected for up to 144 h post dose for pharmacokinetic evaluations. Plasma concentrations of amlodipine, losartan, EXP3174 (an active metabolite of losartan), and rosuvastatin were measured by using liquid chromatography-tandem mass spectrometry. The geometric mean ratio (GMR) and its 90% confidence interval (90% CI) in the FDC treatment to LC treatment for the area under the concentration-time curve from zero to the last quantifiable time point (AUClast) and the maximum plasma concentration (Cmax) were calculated. Safety was monitored throughout the study. Results:The GMR (90% CI) values of AUClast and Cmax were 0.9946 (0.9663-1.0238) and 0.9690 (0.9379-1.0011) for amlodipine, 0.9855 (0.9422-1.0308) and 0.9178 (0.8349-1.0089) for losartan, 0.9814 (0.9501-1.0136) and 0.9756 (0.9313-1.0219) for EXP3174, and 0.9448 (0.8995-0.9923) and 0.9609 (0.8799-1.0494) for rosuvastatin, respectively. No clinically significant changes were observed in any of the safety parameters, including clinical laboratory tests, vital signs, electrocardiograms, and physical examinations, between the FDC treatment and the LC treatment. Conclusion:We confirmed the pharmacokinetic equivalence of the FDC and LC treatments. This triple combination FDC formulation could be a clinically useful replacement for LC therapy.

Project description:PurposeA fixed-dose combination (FDC) of gemigliptin/rosuvastatin 50/20 mg as a monolayer tablet has been used to treat patients with both type 2 diabetes mellitus and dyslipidemia. To improve the stability of the FDC, a new FDC formulation as a bilayer tablet was developed. This study aimed to compare the pharmacokinetics (PKs) and pharmacodynamics (PDs) of the FDC of gemigliptin/rosuvastatin 50/20 mg between the newly developed bilayer tablet and the approved monolayer tablet in healthy subjects.Materials and methodsA randomized, open-label, single-dose, two-treatment, two-way crossover study was conducted. Subjects received a single dose of the FDC of gemigliptin/rosuvastatin 50/20 mg as the bilayer tablet or the monolayer tablet in each period with a 7-day washout. For PK and PD analyses, serial blood samples were collected up to 72 hours after dosing to determine plasma concentrations of gemigliptin, its active metabolite LC15-0636 and rosuvastatin, and plasma dipeptidyl peptidase-4 (DPP-4) activity. PK and PD parameters were calculated using non-compartmental methods and compared between the two formulations.ResultsA total of 48 healthy subjects were randomized, and 45 subjects completed the study. The concentration-time profiles of gemigliptin, LC15-0636 and rosuvastatin were comparable between the two formulations. All geometric mean ratios (90% confidence intervals) of the bilayer tablet to the monolayer tablet for maximum plasma concentration and area under concentration-time curve from 0 to last measurable time point of the three compounds fulfilled the bioequivalence criteria of 0.80-1.25. Likewise, area under plasma DPP-4 activity inhibition from baseline-time curve from 0 to last measurable time point and maximum inhibition of plasma DPP-4 activity were similar between the two formulations.ConclusionThe FDC of gemigliptin/rosuvastatin 50/20 mg as the bilayer tablet showed equivalent PK and PD properties with the FDC of gemigliptin/rosuvastatin 50/20 mg as the monolayer tablet in healthy subjects. These results suggest that the newly developed bilayer tablet can become an alternative formulation to the commercially available monolayer tablet.

Dataset Information

A Fixed-Dose Combination Of Gemigliptin And Rosuvastatin Exhibits Similar Pharmacokinetics, Pharmacodynamics, And Safety Compared To That Of A Loose Combination In Healthy Subjects.

Publications

A Fixed-Dose Combination Of Gemigliptin And Rosuvastatin Exhibits Similar Pharmacokinetics, Pharmacodynamics, And Safety Compared To That Of A Loose Combination In Healthy Subjects.

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