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.

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  • Additional Information
    • Source:
      Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 100883645 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1463-1326 (Electronic) Linking ISSN: 14628902 NLM ISO Abbreviation: Diabetes Obes Metab Subsets: MEDLINE
    • Publication Information:
      Original Publication: Oxford : Wiley-Blackwell, c1999-
    • Subject Terms:
      Biosimilar Pharmaceuticals/*pharmacokinetics ; Diabetes Mellitus, Type 1/*drug therapy ; Hyperglycemia/*prevention & control ; Hypoglycemia/*prevention & control ; Hypoglycemic Agents/*pharmacokinetics ; Insulin Glargine/*analogs & derivatives; Adult ; Biosimilar Pharmaceuticals/adverse effects ; Biosimilar Pharmaceuticals/blood ; Biosimilar Pharmaceuticals/therapeutic use ; Biotransformation ; Blood Glucose/analysis ; Cross-Over Studies ; Diabetes Mellitus, Type 1/blood ; Double-Blind Method ; European Union ; Female ; Glucose Clamp Technique ; Humans ; Hypoglycemia/chemically induced ; Hypoglycemic Agents/adverse effects ; Hypoglycemic Agents/blood ; Hypoglycemic Agents/therapeutic use ; Insulin Glargine/adverse effects ; Insulin Glargine/blood ; Insulin Glargine/pharmacokinetics ; Insulin Glargine/therapeutic use ; Male ; Patient Dropouts ; United States ; Young Adult
    • Abstract:
      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 0-24 and C max of M1) and PD (GIR-AUC 0-24 , GIR-AUC 0-12 , GIR-AUC 12-24 , and GIR max ) 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).
      (© 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)
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    • Contributed Indexing:
      Keywords: biosimilar insulin; glycaemic control; insulin analogues; pharmacodynamics; pharmacokinetics; type 1 diabetes
    • Molecular Sequence:
      ClinicalTrials.gov NCT02059174
    • Accession Number:
      0 (Biosimilar Pharmaceuticals)
      0 (Blood Glucose)
      0 (Hypoglycemic Agents)
      0 (MK-1293)
      2ZM8CX04RZ (Insulin Glargine)
    • Publication Date:
      Date Created: 20170818 Date Completed: 20181227 Latest Revision: 20240313
    • Publication Date:
      20240313
    • Accession Number:
      PMC5813203
    • Accession Number:
      10.1111/dom.13084
    • Accession Number:
      28817223