Pharmacokinetic and Pharmacodynamic Bioequivalence of Proposed Biosimilar MYL-1501D With US and EU Insulin Glargine Formulations in Patients With Type 1 Diabetes Mellitus.

Aims To report phase 1 bioequivalence results comparing MYL-1501D, US reference insulin glargine (US IG), and European reference insulin glargine (EU IG). Materials and methods The double-blind, randomized, three-way crossover study compared the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of MYL-1501D, US IG and EU IG. In total, 114 patients with type 1 diabetes (T1DM) received 0.4 U/kg of each study treatment under automated euglycaemic clamp conditions. Insulin metabolite M1 concentrations, insulin glargine (IG) and glucose infusion rates (GIRs) were assessed over 30 hours. Primary PK endpoints were area under the serum IG concentration-time curve from 0 to 30 hours (AUC(ins.0-30h)) and maximum serum IG concentration (C-ins.max). Primary PD endpoints were area under the GIR-time curve from 0 to 30 hours (AUC(GIR0-30h)) and maximum GIR (GIR(max)). Results Bioequivalence among MYL-1501D, US IG and EU IG was demonstrated for the primary PK and PD endpoints. Least squares mean ratios were close to 1, and 90% confidence intervals were within 0.80 to 1.25. The PD GIR-time profiles were nearly superimposable. There were no noticeable differences in the safety profiles of the three treatments, and no serious adverse events were reported. Conclusions Equivalence with regard to PK and PD characteristics was shown among MYL-1501D, US IG and EU IG in patients with T1DM, and each treatment was well tolerated and safe.