Technosphere Insulin (TI) is an ultra-rapid, short-acting inhaled insulin that provides glycemic control in patients with diabetes. This ongoing, 2-part, open-label, interventional study aims to assess the efficacy and safety of TI in children aged 4 to 17 years with type 1 diabetes mellitus (T1DM) who are on a stable regimen of basal-bolus insulin therapy. Part 1 is a single-arm study that includes evaluation of insulin pharmacokinetics (PK) after a single prandial dose of TI (4, 8, or 12 units), followed by a 4-week titration period. Approximately 46 patients will be enrolled across 3 age cohorts: cohort 1 (13-17 years), cohort 2 (8-12 years), and cohort 3 (4-7 years). As of August 16, 2018, 15 patients had enrolled in cohort 1, 14 had received at least 1 dose, and 8 completed the titration period. Overall, 50% of the safety population (n=14) was female, mean duration of T1DM was 6.2 years, mean age was 15 years, and mean body mass index was 22.4 kg/m2. Initial PK results from cohort 1 demonstrated insulin metabolism similar to that in adult patients receiving TI. Insulin concentrations rapidly increased in the first 30 minutes after TI treatment and returned to baseline by 120 minutes for the 4-, 8-, and 12-unit doses. Mean postprandial glucose levels decreased within 1-hour postdose for the 8- and 12-unit dose groups. Seven patients developed treatment-related cough of mild (6 events) or moderate (1 event) severity. Seven patients experienced a total of 41 hypoglycemic events, but no patient required the assistance of another person to administer corrective carbohydrates. No clinically relevant declines in pulmonary function were reported. Two patients discontinued the study due to adverse events (cough, diabetic ketoacidosis). These data will help determine the appropriate age range for inclusion and recommended dosing for part 2, which will be a 1-year efficacy and safety study.
M.L. Grant: Employee; Self; MannKind Corporation. Stock/Shareholder; Self; MannKind Corporation. J.A. Krueger: Employee; Self; Eli Lilly and Company, MannKind Corporation. Stock/Shareholder; Self; Eli Lilly and Company. M. Fineman: Consultant; Self; MannKind Corporation. Employee; Self; Elcelyx Therapeutics, Inc. Stock/Shareholder; Self; Elcelyx Therapeutics, Inc. G. Sharma: Employee; Self; MannKind Corporation. F. Pompilio: Employee; Self; MannKind Corporation. Stock/Shareholder; Self; Amgen Inc., MannKind Corporation. D.M. Kendall: Employee; Spouse/Partner; Amgen Inc. Employee; Self; MannKind Corporation. Stock/Shareholder; Self; MannKind Corporation.