David Kendall, United States of America
MannKind Corporation Medical AffairsModerator of 1 Session
Presenter of 3 Presentations
SAFETY AND PHARMACOKINETICS OF TECHNOSPHERE INSULIN IN PEDIATRIC PATIENTS
Abstract
Background and Aims
Technosphere Insulin (TI), an ultra-rapid, short-acting inhaled insulin, provides glycemic control in patients with diabetes. This ongoing, 2-part, open-label, interventional study (NCT02527265) aims to assess efficacy and safety of TI in children aged 4 to 17 years with type 1 diabetes (T1D) who are receiving a stable regimen of basal-bolus insulin.
Methods
Part 1, a single-arm study, includes evaluation of insulin pharmacokinetics (PK) after a single prandial dose of TI (4, 8, or 12 U), followed by a 4-week titration period. Approximately 46 patients will be enrolled across 3 cohorts: cohorts 1 (13-17 years), 2 (8-12 years), and 3 (4-7 years).
Results
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-U doses. Mean postprandial glucose levels decreased within 1-hour postdose for the 8- and 12-U doses. Seven patients developed treatment-related cough of mild (6 events) or moderate (1 event) severity; 7 patients experienced a total of 41 hypoglycemic events; no patients required the assistance of another person to administer corrective carbohydrates. No clinically relevant declines in pulmonary function were reported. Two patients discontinued because of adverse events (cough, diabetic ketoacidosis).
Conclusions
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.
TECHNOSPHERE INSULIN PROVIDES BETTER EARLY POSTPRANDIAL GLUCOSE CONTROL THAN SUBCUTANEOUS RAPID-ACTING ANALOGUE
Abstract
Background and Aims
In a recent study (STAT, NCT03143816), patients with type 1 diabetes (T1D) treated with Technosphere Insulin (TI) demonstrated better early postprandial glucose (PPG) control than those on subcutaneous (SC) insulin aspart. The average daily dose of TI in patients who took TI as directed in the protocol was twice that of insulin aspart (40.5 vs 20.6 U). Despite the higher dose, the TI group experienced less time in hypoglycemia than the insulin aspart group. These results prompted a retrospective analysis of mixed-meal tolerance tests (MMTTs) conducted in T1D to further evaluate the 2:1 dosing ratio.
Methods
In study MKC-TI-009 (NCT00308308), patients with T1D underwent 1 to 3 MMTTs. There were 1326 evaluable PPG profiles: 674 MMTTs from 261 patients on insulin aspart and 652 MMTTs from 264 patients on TI.
Results
On average, the area under the PPG excursion curve (PPGE AUC) decreased with increasing dose, and the mean (standard error [SE]) ratio of the insulin aspart slope to the TI slope was 2.1 (0.3), consistent with the results of STAT. This was confirmed when doses of TI 8, 16, and 24 U were compared with mean (SE) insulin aspart doses of 4 (1), 8 (1), and 12 (1) U, respectively (Figure). 
Conclusions
The TI PPGE curves confirm TI has an earlier onset and shorter duration of action, whereas the insulin aspart PPGE curves tend to drop below baseline in the late postprandial period, reflecting a longer duration of action. The timing of hypoglycemia (levels 1 and 2) follows the pattern of PPGEs.