ABSTRACT
INTRODUCTION: Technosphere insulin (TI) is an inhaled dry powder ultra-rapid-acting insulin. This report describes the results of the first study of TI in children with type 1 diabetes (T1D). METHODS: Pharmacokinetics (PK) of TI and the effect of TI on circulating glucose concentrations were evaluated in a single-arm study that enrolled children ages 8-17 years with T1D for more than 1 year, on a stable multiple daily insulin injection (MDI) regimen, and meeting pre-defined pulmonary function testing criteria (at least 70% predicted). To assess PK, subjects received an individualized single preprandial dose of TI (4-12 U, in 4-U increments) via oral inhalation, based on their usual meal-time subcutaneously injected rapid-acting insulin dose and meal content. Serum insulin and blood glucose were measured at - 30 to 250 min relative to dosing. RESULTS: Twenty-seven children with T1D participated in this single-dose PK study. Mean subject age was 13.3 years (59% female; 81.5% White). Mean serum insulin Cmax (maximum concentration) was 77.3, 119.15, and 207.7 µU/mL for doses of 4, 8, and 12 U, respectively. Tmax occurred at 10.5, 13.9, and 14.6 min post-dose for 4, 8, and 12 U. Glucose lowering 30-60 min post-dose was consistent with the PK profile. CONCLUSION: Serum insulin rapidly increased post-dose and returned to baseline by 120 min. The data suggests the PK of TI in youth with T1D ages 8-17 years was similar to that seen in previous adult studies. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02527265.
ABSTRACT
OBJECTIVE: To compare glycemic efficacy of Technosphere insulin (TI) versus that of insulin aspart (IA), each added to basal insulin, in type 2 diabetes. METHODS: This randomized, 24-week trial included subjects aged from 18 to 80 years who were treated with subcutaneous insulin for 3 months and had glycated hemoglobin (HbA1C) levels of 7.0% to 11.5%. After receiving stabilized insulin glargine doses during a 4-week lead in, the subjects were randomized to TI or IA. The primary end point was an HbA1C change from baseline, with the differences analyzed by equivalence analyses. RESULTS: In the overall cohort (N = 309; males, 23.3%), mean (SD) age was 58.5 (8.4) years, body mass index was 30.8 (4.7) kg/m2, weight was 82.2 (13.6) kg, and duration of diabetes was 12.2 (7.1) years. An intention-to-treat cohort had 150 subjects randomized to TI (mean [SD] HbA1C: 8.9% [1.1%]) and 154 randomized to IA (mean [SD] HbA1C: 9.0% [1.3%]). At 24 weeks, mean (SD) HbA1C value declined to 7.9% (1.3%) and 7.7% (1.1%) in the TI and IA cohorts, respectively. A treatment difference of 0.26% was not statistically significant, but the predefined equivalency margin was not met. Subjects receiving TI lost 0.78 kg compared to baseline; subjects receiving IA gained 0.23 kg (P =.0007). The incidence of mild/moderate hypoglycemia was lower for the TI cohort, though not statistically significant. CONCLUSION: Both TI and IA resulted in significant and clinically meaningful HbA1C reductions. TI also resulted in significant and clinically meaningful weight reductions. These data support the use of inhaled insulin as a treatment option for individuals with type 2 diabetes.
Subject(s)
Diabetes Mellitus, Type 2 , Insulin Aspart , Adolescent , Adult , Aged , Aged, 80 and over , Blood Glucose , Diabetes Mellitus, Type 2/drug therapy , Glycated Hemoglobin/analysis , Humans , Hypoglycemic Agents , Insulin , Insulin Glargine , Insulin, Long-Acting , Male , Middle Aged , Young AdultABSTRACT
BACKGROUND: Technosphere Insulin (TI) is an inhaled insulin. Studies comparing TI with short-acting insulin analogues provide important insights on efficacy, dosing, and time course of action. METHODS: Planned enrollment of 230 subjects was limited to 138 due to premature study discontinuation. The primary efficacy endpoint was a noninferiority of glycosylated hemoglobin (HbA1c) of 0.4% for TI compared with insulin lispro (LIS) in a 16-week phase 3 randomized clinical trial in type 1 diabetes mellitus. RESULTS: HbA1c values were similar in the TI and LIS groups at the beginning of the trial (7.8% and 7.6%, respectively) and at trial endpoint (7.7% and 7.6%, respectively). Least squares mean changes from baseline were similar between study groups. Glucose values after a standard meal were significantly lower with TI in the first 90 minutes post meal compared with LIS. Mild or moderate hypoglycemia event rates were also significantly lower with TI compared with LIS (5.97 vs 8.01, respectively; P = .0269). Cough was the most commonly reported adverse event with TI. Pulmonary function as measured by forced expiratory volume in 1 second was not different between groups at baseline, 16 weeks, or 4 weeks off study drug. CONCLUSIONS: HbA1c was unchanged and overall glucose control was comparable between groups. Treatment with TI resulted in improved post-meal glucose and a lower risk of hypoglycemia compared with LIS.
