Clinical Evaluation of MK‐2640: An Insulin Analog With Glucose‐Responsive Properties. Issue 2 (30th September 2018)

• Record Type: Journal Article
• Authors: Krug, Alexander W.; Visser, Sandra A.G.; Tsai, Kuenhi; Kandala, Bhargava; Fancourt, Craig; Thornton, Bob; Morrow, Linda; Kaarsholm, Niels C.; Bernstein, Harold S.; Stoch, S. Aubrey; Crutchlow, Michael; Kelley, David E.; Iwamoto, Marian
• Is Part Of: Clinical pharmacology & therapeutics. Volume 105:Issue 2(2019)
• Page Start: 417
• Page End: 425
• Publication Date: 2018-09-30
• Subjects: Pharmacology -- Periodicals; Therapeutics -- Periodicals; 615.5
• DOI: 10.1002/cpt.1215
• Languages: English
• ISSNs: 0009-9236

Abstract

Abstract : The goal of this investigation was to examine clinical translation of glucose responsiveness of MK‐2640, which is a novel insulin saccharide conjugate that can bind the insulin receptor or mannose receptor C type 1 (MRC1), the latter dependent upon glucose concentration. In a rising dose study in 36 healthy adults under euglycemic clamp conditions, rising exposures revealed saturation of MK‐2640 clearance, likely due to saturation of clearance by MRC1. Potency of MK‐2640 was ~25‐fold reduced relative to regular human insulin. In a randomized, 2‐period crossover trial in 16 subjects with type 1 diabetes mellitus to evaluate glucose‐responsiveness of i.v. administered MK‐2640, we were unable to demonstrate a glucose‐dependent change in MK‐2640 clearance, although a significant glucose‐dependent augmentation of glucose infusion rate was observed. These pharmacokinetic (PK) and pharmacodynamic (PD) data provide crucial insights into next steps for developing an insulin saccharide conjugate as a clinically effective glucose‐responsive insulin analog.