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Randomized Controlled Trial
. 2020 Apr;22(4):521-529.
doi: 10.1111/dom.13919. Epub 2019 Dec 15.

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

Tim Heise  1 , Charles Donnelly  2 , Abhijit Barve  3 , Patrick Aubonnet  4
Affiliations
Randomized Controlled Trial

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

Tim Heise et al. Diabetes Obes Metab. 2020 Apr.

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.

Keywords: bioequivalence; biosimilar; diabetes; insulin; insulin glargine; pharmacodynamics; pharmacokinetics; phase 1; type 1 diabetes mellitus.

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Conflict of interest statement

T.H. is a member of advisory panels for Novo Nordisk and Mylan Inc., has received speaker honoraria and travel grants from Eli Lilly and Novo Nordisk, and his institution has received research funds from Adocia, Boehringer Ingelheim, Biocon Ltd, Dance Pharmaceuticals, Eli Lilly, Gan & Lee Pharmaceuticals, Johnson & Johnson, Mars, MedImmune, Mylan Inc., Nordic Bioscience, Novo Nordisk, Pfizer, Poxel, Saniona, Sanofi, Wockhardt, and Zealand Pharma. C.D., A.B. and P.A. are paid employees of Mylan Inc. and may hold stock in the company.

Figures

Figure 1
Figure 1
A, Mean smoothed serum insulin glargine (IG) profiles (enzyme‐linked immunosorbent assay), B, mean plasma metabolite M1 profiles (liquid chromatography with tandem mass spectrometry), and C, mean smoothed glucose infusion rate (GIR) profiles of the three IG preparations in linear scale from injection at time 0 minutes to end of clamp procedure at 30 hours. EU IG, European reference insulin glargine; US IG, US reference insulin glargine
See this image and copyright information in PMC

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