Abstract
AIMS/INTRODUCTION: Ultra-rapid lispro (URLi) is a novel ultra-rapid mealtime insulin. This study compared the pharmacokinetic and glucodynamic profiles, safety, and tolerability of URLi and lispro (Humalog(®) ) in Japanese patients with type 1 diabetes mellitus. MATERIALS AND METHODS: This was a phase I, single center, randomized, patient- and investigator-blind, two-period, cross-over study. A total of 31 patients received a single subcutaneous 15-U dose of URLi or lispro before undergoing a euglycemic clamp procedure. Primary pharmacokinetic endpoints were the time to early half-maximal drug concentration and the area under the concentration versus time curve from 0 to 30 min postdose. The glucodynamic endpoints were the time to early half-maximal glucose infusion rate before time to maximum glucose infusion rate, and the time to onset of insulin action. RESULTS: URLi showed accelerated insulin lispro absorption compared with lispro, as shown by a decrease of 56% (URLi: 10.2 min, lispro: 23.3 min; P < 0.0001) in the early half-maximal drug concentration, and a 2.4-fold increase in the area under the concentration versus time curve from 0 to 30 min (P < 0.0001). The duration of insulin lispro exposure was 88 min shorter after URLi administration compared with lispro. URLi reduced the early half-maximal glucose infusion rate before time to maximum glucose infusion rate and the time to onset of insulin action significantly compared with lispro. The glucose infused within the first 30 min of the clamp was 2.16-fold greater with URLi compared with lispro. There was no difference in total exposure or glucose infused between treatments. All treatment-emergent adverse events were mild/moderate in severity. CONCLUSIONS: In Japanese type 1 diabetes mellitus patients, URLi showed accelerated insulin lispro absorption, reduced late exposure, overall shorter duration and faster early insulin action compared with lispro.