Abstract
INTRODUCTION: We investigated the safety of, and glucose control by, the insulin-only configuration of the iLet(®) bionic pancreas delivering fast-acting insulin aspart (faster aspart), using the same insulin-dosing algorithm but different time to maximal serum drug concentration (t(max)) settings, in adults with type 1 diabetes. METHODS: We performed a single-center, single-blinded, crossover (two 7-day treatment periods) escalation trial over three sequential cohorts. Participants from each cohort were randomized to a default t(max) setting (t(65) [t(max) = 65 min]) followed by a non-default t(max) setting (t(50) [t(max) = 50 min; cohort 1], t(40) [t(max) = 40 min; cohort 2], t(30) [t(max) = 30 min; cohort 3]), or vice versa, all with faster aspart. Each cohort randomized eight new participants if escalation-stopping criteria were not met in the previous cohort. RESULTS: Overall, 24 participants were randomized into three cohorts. Two participants discontinued treatment, one due to reported 'low blood glucose' during the first treatment period of cohort 3 (t(30)). Mean time in low sensor glucose (< 54 mg/dl, primary endpoint) was < 1.0% for all t(max) settings. Mean sensor glucose in cohorts 1 and 2 was significantly lower at non-default versus default t(max) settings, with comparable insulin dosing. The mean time sensor glucose was in range (70-180 mg/dl) was > 70% for all cohorts, except the default t(max) setting in cohort 1. No severe hypoglycemic episodes were reported. Furthermore, there were no clinically significant differences in adverse events between the groups. CONCLUSION: There were no safety concerns with faster aspart in the iLet at non-default t(max) settings. Improvements were observed in mean sensor glucose without increases in low sensor glucose at non-default t(max) settings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03816761.