Similar Pharmacokinetics and Pharmacodynamics of Biosimilar SAR342434 Insulin Lispro and Japan-Approved Humalog Insulin Lispro in Healthy Japanese Subjects.

This phase 1 study compared the pharmacokinetic (PK) and glucose pharmacodynamic (PD) characteristics of biosimilar SAR342434 insulin lispro and Japan-reference Humalog insulin lispro. This was a randomized, double-blind, 2-period, crossover study. Thirty-six healthy Japanese male subjects underwent a 10-hour euglycemic clamp following a single subcutaneous 0.3-U/kg dose of SAR342434 or Humalog. Insulin lispro concentration and blood glucose were measured, and the glucose infusion rate (GIR) was adjusted to maintain the target blood glucose level. Primary PK end points were maximum plasma insulin lispro concentration and area under the plasma insulin concentration-time curve (AUC) from time 0 to the last quantifiable concentration. Primary PD end points were area under the GIR-time curve from time 0 to 10 hours and maximum GIR. PK exposure (maximum plasma concentration and AUC from time 0 to the last quantifiable concentration) and PD activity (GIR-AUC from time 0 to 10 hours and maximum GIR) were similar between treatments. Geometric mean ratios were close to 1, and the corresponding 90% and 95%CIs (PK and PD activity, respectively) were within the 0.80 to 1.25 equivalence range. SAR342434 and Humalog were well tolerated. In healthy Japanese males, SAR342434 and Humalog showed similar PK exposure profiles and PD potency, in support of SAR342434 use as a biosimilar product.

Pharmacokinetic and pharmacodynamic similarity between SAR341402 insulin aspart and Japan-approved NovoRapid in healthy Japanese subjects.

This study compared the pharmacokinetic and glucodynamic profiles of biosimilar SAR341402 insulin aspart to Japan-approved insulin aspart (NovoRapid) in healthy Japanese males. In this single-center, randomized, double-blind, single-dose, two-period, crossover study, subjects received 0.3 U/kg of SAR341402 or NovoRapid before undergoing a 10 h euglycemic clamp procedure. Plasma insulin aspart concentrations and blood glucose levels were measured, and glucose infusion rates (GIRs) were assessed. Primary endpoints were maximum plasma insulin aspart concentration (INS-Cmax), area under the plasma insulin concentration-time curve to the last quantifiable concentration (INS-AUClast), area under the GIR-time curve during the clamp (GIR-AUC0-10 h), and maximum GIR (GIRmax). Forty subjects were randomized with 39 completing both treatment periods. Pharmacokinetic exposure showed a mean ratio between products of 1.00 (90% confidence interval [CI] 0.94-1.05) for INS-Cmax and 1.02 (90% CI 1.00-1.04) for INS-AUClast. Glucodynamic activity showed a mean ratio between products of 1.00 (95% CI 0.93-1.06) for GIR-AUC0-10 h and 1.01 (95% CI 0.95-1.08) for GIRmax. The 90% CIs for pairwise treatment ratios were within the predefined equivalence range of 0.80-1.25. Both treatments were well tolerated. We concluded that similar pharmacokinetic exposure and glucodynamic potency were shown for SAR341402 and NovoRapid in healthy Japanese males.

Effect of a single dose of insulin glargine/lixisenatide fixed ratio combination (iGlarLixi) on postprandial glucodynamic response in Japanese patients with type 2 diabetes mellitus: A phase I randomized trial.

This report describes novel clinical data assessing the pharmacodynamics of insulin glargine/lixisenatide (iGlarLixi) compared with placebo and insulin glargine alone, to determine pharmacokinetics of lixisenatide, and to assess safety of iGlarLixi in Japanese people with type 2 diabetes mellitus (T2DM). In a single-centre, open-label, randomized, placebo-controlled cross-over study, participants received subcutaneous iGlarLixi 5 U/5 µg and 10 U/10 µg, placebo, and 5 U insulin glargine. The primary endpoint was area under the postprandial plasma glucose (PPG) curve (AUC0-2h ). A total of 20 participants completed all study periods. iGlarLixi 5 U/5 µg and 10 U/10 µg reduced mean PPG dose-dependently compared with placebo and insulin glargine 5 U. Both combinations significantly reduced PPG-AUC0-2h dose-dependently compared with placebo (least squares mean difference -7.48 mmol h/L for 5 U/5 µg, -10.75 mmol h/L for 10 U/10 µg; P < 0.0001). iGlarLixi 5 U/5 µg reduced PPG-AUC0-2h significantly compared with insulin glargine 5 U (-0.76 mmol h/L; P < 0.0001). No symptomatic hypoglycaemia occurred during the study. iGlarLixi single subcutaneous injections significantly and dose-dependently reduced PPG compared to placebo or insulin glargine in Japanese participants with T2DM. iGlarLixi was safe and well tolerated, and would be expected to provide the 24-hour plasma glucose-lowering effects of insulin glargine and the postprandial antihyperglycaemic effects of lixisenatide.