LAUSR

Imeglimin is a diabetic drug excreted mainly in the urine; therefore, the impact of renal impairment on its pharmacokinetics (PK) is of interest. We assessed the PK and safety of imeglimin in Japanese patients with impaired renal function. This was an uncontrolled, open-label, single-dose, phase 1 study. Participants were classified into four groups by their estimated glomerular filtration rate (eGFR; mL/min/1.73m2 ) as follows: ≥90, normal renal function; and 60-<90, 30-<60, and 15-<30, mild, moderate, and severe renal impairment, respectively. All participants received imeglimin 1000 mg except those with severe renal impairment who received imeglimin 500 mg. PK parameters were estimated using non-compartmental analysis and those after multiple administrations were projected using a non-compartmental superposition method. In total, 24 Japanese participants (six in each group) were enrolled and completed the study. The mean plasma imeglimin concentration reached the maximum at 2-4 hours after administration and then rapidly decreased. The geometric mean maximum observed plasma concentration (Cmax ) and area under the curve (AUC) values were higher in the impaired renal function groups versus normal renal function group. Most imeglimin was excreted in urine by 24 hours post-administration. Renal clearance decreased with decreasing renal function. Projected Cmax and AUC0-τ after multiple dosing were greater in the renal impairment groups versus normal renal function group. No adverse events were observed. Considering increased plasma exposure along with decreased renal clearance, dose adjustment is required in patients with moderate and severe renal impairment with eGFR of 15-<45 mL/min/1.73 m2 . This article is protected by copyright. All rights reserved.