Steven J Russell1,2, Courtney Balliro3, Magnus Ekelund4, Firas El-Khatib5,6, Tina Graungaard7, Evelyn Greaux3, Mallory Hillard3, Rabab Z Jafri3,8, Naveen Rathor9, Raj Selagamsetty5,6, Jordan Sherwood3, Edward R Damiano5. 1. Diabetes Research Center, Massachusetts General Hospital, Boston, MA, USA. SJRUSSELL@mgh.harvard.edu. 2. Diabetes Research Unit, Massachusetts General Hospital, Boston, MA, USA. SJRUSSELL@mgh.harvard.edu. 3. Diabetes Research Center, Massachusetts General Hospital, Boston, MA, USA. 4. Type 1 Diabetes and Functional Insulins, Novo Nordisk A/S, Søborg, Denmark. 5. Department of Biomedical Engineering, Boston University, Boston, MA, USA. 6. Research and Innovation, Beta Bionics, Inc., Boston, MA, USA. 7. Biostatistics, Novo Nordisk A/S, Aalborg, Denmark. 8. Division of Pediatric Endocrinology, University of Texas Health Science Center, San Antonio, TX, USA. 9. Novo Nordisk Service Centre India Private Ltd., Bangalore, India.
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 (tmax) 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 tmax setting (t65 [tmax = 65 min]) followed by a non-default tmax setting (t50 [tmax = 50 min; cohort 1], t40 [tmax = 40 min; cohort 2], t30 [tmax = 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 (t30). Mean time in low sensor glucose (< 54 mg/dl, primary endpoint) was < 1.0% for all tmax settings. Mean sensor glucose in cohorts 1 and 2 was significantly lower at non-default versus default tmax 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 tmax 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 tmax settings. Improvements were observed in mean sensor glucose without increases in low sensor glucose at non-default tmax settings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03816761.
RCT Entities:
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 (tmax) 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 tmax setting (t65 [tmax = 65 min]) followed by a non-default tmax setting (t50 [tmax = 50 min; cohort 1], t40 [tmax = 40 min; cohort 2], t30 [tmax = 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 (t30). Mean time in low sensor glucose (< 54 mg/dl, primary endpoint) was < 1.0% for all tmax settings. Mean sensor glucose in cohorts 1 and 2 was significantly lower at non-default versus default tmax 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 tmax 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 tmax settings. Improvements were observed in mean sensor glucose without increases in low sensor glucose at non-default tmax settings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03816761.
Authors: Roy W Beck; Steven J Russell; Edward R Damiano; Firas H El-Khatib; Katrina J Ruedy; Courtney Balliro; Zoey Li; Peter Calhoun Journal: Diabetes Technol Ther Date: 2022-10 Impact factor: 7.337