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Pharmacokinetic and pharmacodynamic bioequivalence of proposed biosimilar MYL-1501D with US and European insulin glargine formulations in patients with type 1 diabetes mellitus.

ABSTRACT: 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 (AUCins.0-30h ) and maximum serum IG concentration (Cins.max ). Primary PD endpoints were area under the GIR-time curve from 0 to 30?hours (AUCGIR0-30h ) and maximum GIR (GIRmax ). 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.

SUBMITTER: Heise T

PROVIDER: S-EPMC7079113 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Pharmacokinetic and pharmacodynamic bioequivalence of proposed biosimilar MYL-1501D with US and European insulin glargine formulations in patients with type 1 diabetes mellitus.

Heise Tim T Donnelly Charles C Barve Abhijit A Aubonnet Patrick P

Diabetes, obesity & metabolism 20191215 4

<h4>Aims</h4>To report phase 1 bioequivalence results comparing MYL-1501D, US reference insulin glargine (US IG), and European reference insulin glargine (EU IG).<h4>Materials and methods</h4>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 ...[more]

PMID: 31724253

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Project description:Insulin glargine is a long-acting insulin analog, which plays an important role in the treatment of diabetes mellitus. Biosimilar products of insulin glargine can provide patients with additional safe, high-quality, and potentially cost-effective options for treating diabetes. This article presents a randomized, double-blind, single-dose, two-treatment, four-period, replicate crossover, euglycemic clamp study which was designed to evaluate the PK and PD similarity between the recombinant insulin glargine developed by Wanbang (test) and Lantus® (reference) in healthy volunteers. Subjects received subcutaneous administration of the insulin glargine formulation (0.4 U/kg) on two occasions for the test and reference drug, respectively, and a 20% dextrose solution was infused at variable rate to clamp the blood glucose concentrations at 0.3 mmol/L below the subjects' fasting glucose for 24 h. Taking advantage of the improved sensitivity of the bioanalytical method applied and the solution of the matrix stability problem, the parent insulin glargine was determined in the vast majority of plasma samples using a fully validated UHPLC-MS/MS method. The PK characteristics of the parent insulin glargine were revealed for the first time: after subcutaneous injection, concentrations of the parent insulin glargine increased to a relative high level within 3 h, and then, a relatively flat concentration-time profile lasting for at least 12 h post-dose was observed. For the first time, the pharmacokinetic parameters of the parent insulin glargine were used as endpoints for similarity evaluation, which complied with the regulatory guidance better and made the similarity conclusion more powerful. The ratios of geometric means of all PK and PD endpoints were close to 100.00%. For the PK endpoints (AUC0-24h, Cmax, AUC0-12h, and AUC12-24h of the parent insulin glargine and its metabolite M1), the 90% confidence intervals of geometric mean ratios of test to reference were entirely contained within 80.00%-125.00%. For the PD endpoints [AUCGIR(0-24h), GIRmax, AUCGIR(0-12h), and AUCGIR(12-24h)], the 95% confidence intervals of geometric mean ratios of test to reference were entirely contained within 80.00%-125.00%. Based on the above mentioned results, it can be concluded that the PK and PD characteristics of the biosimilar drug developed by Wanbang are similar to those of Lantus.

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Dataset Information

Pharmacokinetic and pharmacodynamic bioequivalence of proposed biosimilar MYL-1501D with US and European insulin glargine formulations in patients with type 1 diabetes mellitus.

Publications

Pharmacokinetic and pharmacodynamic bioequivalence of proposed biosimilar MYL-1501D with US and European insulin glargine formulations in patients with type 1 diabetes mellitus.

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