JLP-2008 Fixed-Dose Combination Tablet Demonstrates Bioequivalence and Comparable Safety to Separate Dapagliflozin +...

To establish pharmacokinetic bioequivalence and assess the safety of a single-dose administration of fixed-dose combination (FDC) tablet containing dapagliflozin 10 mg + pioglitazone 15 mg (JLP-2008) compared with a single-dose administration of their individual tablets.

In this randomized, open-label, two-period crossover study, 49 healthy Korean adults were enrolled, 48 received at least one dose and 45 completed both periods. Participants received either one JLP-2008 tablet or separate dapagliflozin + pioglitazone tablets under fasting conditions, then the alternate treatment after a 7-day washout. Blood samples collected predose to 48 h were quantified by ultra-fast liquid chromatography-tandem mass spectrometry. Primary endpoints were maximum plasma concentration (C_max) and area under the plasma concentration-time curve from zero until the last measurable concentration (AUC_last) for each analyte; bioequivalence was concluded if 90% confidence intervals (CIs) for test/reference geometric mean ratios (GMRs) lay within 80.00-125.00%. Adverse events (AEs), vital signs, laboratories, blood glucose, and 12-lead electrocardiogram (ECGs) were monitored for safety assessment.

Dapagliflozin and pioglitazone met bioequivalence criteria: GMRs (90% CIs) were 1.04 (0.95-1.15) for dapagliflozin C_max, 1.05 (1.02-1.08) for dapagliflozin AUC_last, 0.94 (0.85-1.04) for pioglitazone C_max and 0.93 (0.87-1.00) for pioglitazone AUC_last, each within the 80.00-125.00% acceptance range. Hydroxy pioglitazone (M-IV), an active metabolite, also met the criteria: C_max, 0.94 (0.89-1.00) and AUC_last, 0.93 (0.88-0.98). Twenty-seven treatment-emergent AEs were recorded (test = 13 in 9 participants; reference = 14 in 9 participants); all were mild or moderate, non-serious, and incidence did not differ between treatments. No clinically meaningful hypoglycemia, ECG changes, or laboratory abnormalities were observed.

JLP-2008 delivers systemic exposures to dapagliflozin and pioglitazone equivalent to those from co-administration of individual tablet and is well tolerated. FDC may provide a more convenient treatment option for patients with type 2 diabetes mellitus (T2DM), and its use was supported by comparable pharmacokinetic and safety profiles.

ClinicalTrials.gov (NCT06165965; retrospectively registered on 07 December 2023).