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) and pharmacodynamic (PD) similarity of LY IGlar and the European Union- and US-approved versions of 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 of two different insulin glargine products on two occasions each, following a randomized sequence. A ≥7-day washout period separated the doses. Blood samples were collected predose and up to 24 h postdose to assess PK; PD was assessed by a euglycemic clamp lasting up to 24 h.
Results: A total of 211 subjects participated in the three studies. The PK (area under the curve [AUC]; maximum observed concentration [Cmax]) and PD (maximum glucose infusion rate [Rmax]; total glucose infusion during the clamp [Gtot]) were similar between LY IGlar and IGlar, with the ratios of geometric means ranging from 0.90 to 0.95 for PK parameters and from 0.91 to 0.99 for PD parameters across studies. In all cases, the 90% CIs for the ratios of geometric means were completely contained in the prespecified acceptance limits of 0.80-1.25. Adverse events were similar between treatments.
Conclusions: These studies demonstrated that the PK and PD properties of LY IGlar and IGlar were similar after single 0.5 units/kg s.c. doses in healthy subjects, contributing to the totality of evidence supporting similarity of these products.
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