Single-dose euglycaemic clamp studies demonstrating pharmacokinetic and pharmacodynamic similarity between MK-1293 insulin glargine and originator insulin glargine (Lantus) in subjects with type 1 diabetes and healthy subjects.
Michael F Crutchlow, John S Palcza, Kate M Mostoller, Chantal D Mahon, April M Barbour, Michael C Marcos, Yang Xu, Elaine Watkins, Linda Morrow, Marcus Hompesch
Author Information
Michael F Crutchlow: Merck & Co., Inc, Kenilworth, New Jersey. ORCID
John S Palcza: Merck & Co., Inc, Kenilworth, New Jersey.
Kate M Mostoller: Merck & Co., Inc, Kenilworth, New Jersey.
Chantal D Mahon: Merck & Co., Inc, Kenilworth, New Jersey.
April M Barbour: Merck & Co., Inc, Kenilworth, New Jersey.
Michael C Marcos: Merck & Co., Inc, Kenilworth, New Jersey.
Yang Xu: Merck & Co., Inc, Kenilworth, New Jersey.
AIMS: MK-1293 is an insulin glargine that has an amino acid sequence identical to that of Lantus, the originator insulin glargine. Two euglycaemic clamp studies, 1 in subjects with type 1 diabetes (T1D) and 1 in healthy subjects, were conducted to demonstrate pharmacokinetic (PK) and pharmacodynamic (PD) similarity between MK-1293 and Lantus commercially procured in both the European Union (EU-Lantus) and the USA (US-Lantus). MATERIALS AND METHODS: Both studies were single-dose, randomized, double-blind, single-centre, crossover studies with ≥7 days between dosing periods. A 2-treatment, 4-period replicate crossover study in T1D subjects (N = 76) compared the PK and PD of MK-1293 to EU-Lantus for 30 hours after dosing. A 3-period crossover study in healthy subjects (N = 109) compared the PK and PD of MK-1293, EU-Lantus and US-Lantus for 24 hours after dosing. In both studies, all subjects received single 0.4 units/kg subcutaneous doses of MK-1293 or Lantus in all dosing periods. Pharmacokinetic assessment was based on LC-MS/MS-based measurement of the major insulin glargine metabolite (M1) and PD was characterized using the euglycaemic clamp platform. RESULTS: In both studies, pre-specified similarity criteria were met between MK-1293 and Lantus for comparison of PK (AUC and C of M1) and PD (GIR-AUC , GIR-AUC , GIR-AUC , and GIR ) primary endpoints. All treatments were well tolerated. CONCLUSION: Based on comparative assessment in both T1D and healthy subjects, it can be concluded that the PK and PD properties of MK-1293 are highly similar to those of Lantus. (ClinicalTrials.gov: NCT02059174).
