Format

Send to

Choose Destination
Diabetes Obes Metab. 2019 Nov 13. doi: 10.1111/dom.13919. [Epub ahead of print]

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

Author information

1
Profil, Neuss, Germany.
2
Mylan Inc., Morgantown, WV, USA.
3
Mylan Inc., Canonsburg, PA, USA.
4
Mylan EPD, Steinhausen, Switzerland.

Abstract

AIMS:

Insulin glargine (IG) is a long-acting insulin analogue indicated for once-daily subcutaneous administration in patients with type 1 and type 2 diabetes mellitus (T1DM and T2DM). MYL-1501D is a proposed IG biosimilar. This study reports phase 1 bioequivalence results comparing MYL-1501D, US reference IG (US IG), and European reference IG (EU IG).

MATERIALS AND METHODS:

The double-blind, randomized, 3-way crossover study compared pharmacokinetics (PK) and pharmacodynamics (PD) of MYL-1501D, US IG, and EU IG. In total, 114 patients with T1DM received 0.4 U/kg of each study treatment under automated euglycemic clamp conditions. Insulin metabolite M1 concentrations, 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% CIs 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 3 treatments, and no serious adverse events were reported.

CONCLUSIONS:

Pharmacokinetic and PD equivalence was shown among MYL-1501D, US IG, and EU IG in patients with T1DM, and each treatment was well tolerated and safe. This article is protected by copyright. All rights reserved.

KEYWORDS:

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

PMID:
31724253
DOI:
10.1111/dom.13919

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center