Comparison of the Pharmacokinetics and Pharmacodynamics of LY2963016 Insulin Glargine and EU- and US-Approved Versions of Lantus Insulin Glargine in Healthy Subjects: Three Randomized Euglycemic Clamp Studies

• DOI: 10.2337/dc14-2623
• Publication Date: 2015-08-26T02:24:42Z
• Authors: Helle Linnebjerg; Eric Chen Quin Lam; Mary E. Seger; David Coutant; Laiyi Chua; Chew Lan Chong; Maria M. Ferreira; Danny Soon; Xin Zhang
• Keywords: Crossover study; Bioequivalence; Pharmacodynamics

OBJECTIVE LY2963016 (LY IGlar) and Lantus (IGlar) are insulin glargine products manufactured by distinct processes but with identical amino acid sequences. Three studies evaluated the pharmacokinetic (PK) pharmacodynamic (PD) similarity of LY IGlar European Union– US-approved versions IGlar. RESEARCH DESIGN AND METHODS These were three single-site, randomized, double-blind, two-treatment, four-period, crossover, euglycemic clamp studies. In each study, fasted healthy subjects received 0.5 units/kg s.c. doses two different on occasions each, following a randomized sequence. A ≥7-day washout period separated doses. Blood samples collected predose up to 24 h postdose assess PK; PD was assessed lasting h. RESULTS total 211 participated in The PK (area under curve [AUC]; maximum observed concentration [Cmax]) (maximum glucose infusion rate [Rmax]; during [Gtot]) similar between IGlar, ratios geometric means ranging from 0.90 0.95 for parameters 0.91 0.99 across all cases, 90% CIs completely contained prespecified acceptance limits 0.80–1.25. Adverse events treatments. CONCLUSIONS demonstrated that properties after single subjects, contributing totality evidence supporting these products.