Journal Article

Racial Comparison of the Pharmacokinetics and Safety of Fixed-dose Combination of Dapagliflozin/Sitagliptin in Western and Korean Healthy Adults

Karlsson, Cecilia, Lukka, Pradeep B., Heijer, Maria, Conrad, Tom, Hammarstedt, Ann, Boulton, David W., Tang, Weifeng

2024

Overview

•Fixed-dose combination (FDC) was bioequivalent to individual components (ICs) in Western and Korean adults.•Pharmacokinetic parameters of FDC and IC were generally similar.•No clinically relevant pharmacokinetic differences in Western vs Korean participants.•FDC and ICs were well tolerated, with no serious adverse events. We evaluated the pharmacokinetics, safety, and tolerability of a fixed-dose combination (FDC) of dapagliflozin/sitagliptin versus individual component (IC) tablets in healthy Western and Korean participants. The combination of these antihyperglycemic drugs provides efficient glucose control, and the use of FDC has generally been shown to improve medication adherence in individuals with type 2 diabetes mellitus (T2DM). Two randomized, open-label, two-period, two-treatment, single-dose, single-center, crossover bioequivalence studies conducted on healthy fasted German participants (aged 18–55 years; Western study) and South Korean participants (aged 19–55 years; Korean study) were included. In both studies, pharmacokinetic parameters (maximum [peak] plasma concentration [Cmax], area under the plasma concentration–time curve from zero to the last quantifiable concentration [AUClast], and area under the plasma concentration–time curve from zero to infinity [AUCinf]) were used to assess the bioequivalence of 10 mg dapagliflozin/100 mg sitagliptin FDC (Treatment A) with their ICs (Treatment B) under fasted conditions. Safety and tolerability were assessed throughout the study. Forty-six healthy participants (male, 60.9%; mean age, 39.5 years; mean body mass index [BMI], 23.9 kg/m2) were randomized in the Western study, and 51 healthy participants (male, 100.0%; mean age, 24.6 years; mean BMI, 23.9 kg/m2) were randomized in the Korean study. In both studies, the participants were randomized 1:1 into treatment sequence AB and treatment sequence BA. Dapagliflozin/sitagliptin FDC was bioequivalent to IC tablets in both Western and Korean studies, as the 90% confidence interval of the FDC to IC ratios of the geometric least-squares means of the pharmacokinetic parameters for both dapagliflozin and sitagliptin was within the 0.8000–1.2500 bioequivalence criterion limit. The observed differences in pharmacokinetic parameters, such as Cmax, AUClast, and AUCinf, between the Western and Korean studies were not clinically meaningful. Dapagliflozin/sitagliptin FDC and their ICs were well tolerated, with no serious adverse events reported in any of the study populations. The 10 mg dapagliflozin/100 mg sitagliptin FDC and IC formulations were bioequivalent in fasted healthy Western and Korean participants, with no new safety concerns identified, thus offering a useful alternative for patients currently receiving individual medications as part of their treatment regimen. Western study (clinicaltrials.gov: NCT05266404) and Korean study (clinicaltrials.gov: NCT05453786).

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: Adolescent / Adult / Antidiabetics / Area Under Curve / Asian People / Benzhydryl Compounds - administration & dosage / Benzhydryl Compounds - adverse effects / Benzhydryl Compounds - pharmacokinetics / Body mass index / Clinical medicine / Cross-Over Studies / Dapagliflozin / Diabetes / Diabetes mellitus (non-insulin dependent) / Dipeptidyl peptidase 4 inhibitor / Drug Combinations / Drug dosages / Female / Females / Fixed-dose combination / Germany / Glucagon / Glucose / Glucosides - administration & dosage / Glucosides - adverse effects / Glucosides - pharmacokinetics / Healthy Volunteers / Heart failure / Humans / Hypoglycemia / Hypoglycemic Agents - administration & dosage / Hypoglycemic Agents - adverse effects / Hypoglycemic Agents - pharmacokinetics / Informed consent / Insulin / Internal Medicine / Male / Middle Aged / Pharmacokinetics / Plasma / Population studies / Republic of Korea / Sitagliptin / Sitagliptin Phosphate - administration & dosage / Sitagliptin Phosphate - adverse effects / Sitagliptin Phosphate - pharmacokinetics / Sodium-glucose co-transporter-2 inhibitor / Tablets / Therapeutic Equivalency / White People / Young Adult