ABSTRACT
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 4 groups by their estimated glomerular filtration rate (mL/min/1.73 m2 ) as follows: ≥90, normal renal function; and 60 to <90, mild; 30 to <60, moderate; and 15 to <30, severe renal impairment. All participants received imeglimin 1000 mg except those with severe renal impairment, who received imeglimin 500 mg. PK parameters were estimated using noncompartmental analysis, and those after multiple administrations were projected using a noncompartmental superposition method. In total, 24 Japanese participants (6 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 and area under the plasma concentration-time curve values were higher in the impaired renal function groups versus normal renal function group. Most imeglimin was excreted in urine by 24 hours after administration. Renal clearance decreased with decreasing renal function. Projected maximum observed plasma concentration and area under the plasma concentration-time curve over the dosing interval 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 estimated glomerular filtration rate of 15 to <45 mL/min/1.73 m2 .
