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.
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 (AUC0-24 and Cmax of M1) and PD (GIR-AUC0-24 , GIR-AUC0-12 , GIR-AUC12-24 , and GIRmax ) 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).
['Crutchlow|Michael F|MF|0000-0002-9686-9047', 'Palcza|John S|JS|', 'Mostoller|Kate M|KM|', 'Mahon|Chantal D|CD|', 'Barbour|April M|AM|', 'Marcos|Michael C|MC|', 'Xu|Yang|Y|', 'Watkins|Elaine|E|', 'Morrow|Linda|L|', 'Hompesch|Marcus|M|']
D000328:Adult D059451:Biosimilar Pharmaceuticals D001711:Biotransformation D001786:Blood Glucose D018592:Cross-Over Studies D003922:Diabetes Mellitus, Type 1 D004311:Double-Blind Method D005062:European Union D005260:Female D015309:Glucose Clamp Technique D006801:Humans D006943:Hyperglycemia D007003:Hypoglycemia D007004:Hypoglycemic Agents D000069036:Insulin Glargine D008297:Male D010352:Patient Dropouts D014481:United States D055815:Young Adult
pharmacokinetics pharmacodynamics type 1 diabetes biosimilar insulin glycaemic control insulin analogues