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DOI: 10.1055/s-0035-1549750
A single-dose pharmacokinetic study of basal insulin peglispro (BIL) in subjects with hepatic impairment
Introduction: BIL is a novel, PEGylated basal insulin lispro with large hydrodynamic size. It has a prolonged duration of action. LY2605541 pharmacokinetics (PK) were compared in subjects with varying degrees of hepatic impairment (HI) and healthy subjects.
Methods: In this parallel-group, open-label study, 35 subjects received a single 0.33U/kg subcutaneous dose of BIL. Serum was obtained for up to 9 days postdose and analysed using ELISA. BIL PK parameters were calculated using noncompartmental analyses and compared between healthy and HI subjects.
Results: 35 subjects were assessed (12 healthy; 8 mild, 8 moderate, 7 severe HI, using Child-Pugh criteria). Subjects were nondiabetic except one with T2DM, 57% males, aged 41 – 69 years, mean (SD) BMI 27.7 (4.52)kg/m2. Healthy subjects were matched to HI subjects for age, weight and gender. LS geometric mean ratios (90% CI) for AUC (0-∞) for mild, moderate, and severe HI subjects to healthy subjects were 0.789 (0.556, 1.12), 0.744 (0.525,1.06), and 0.782 (0.543,1.12), respectively. Ratios (90% CI) for Cmax were 0.728 (0.398,1.33), 0.905 (0.495,1.65), and 0.840 (0.448,1.58), respectively. Median time of Cmax and mean half-life were similar between groups. Five healthy subjects reported 7 treatment-emergent adverse events (TEAEs) and 5 HI subjects reported 7 TEAEs. Most TEAEs were mild.
Conclusion: Single-dose LY2605541 was well tolerated by all groups. A substantial overlap of AUC (0-∞) and Cmax was observed across all groups; ratios between HI and healthy subjects were not statistically different. Based on these data, requirement for BIL dose adjustment in subjects with HI would not be anticipated.