Inhaled Technosphere Insulin in Children with Diabetes: The INHALE-1 Extension Study

Background: On completion of the INHALE-1 randomized controlled trial (RCT), an extension phase was completed to provide longer term safety data on use of technosphere insulin (TI) in children with diabetes. Methods: In the RCT, 4- to 17-yr-olds with type 1 (98%) or type 2 (2%) diabetes treated with multiple daily injections of insulin were randomly assigned to TI or rapid-acting analog (RAA) plus continuation of long-acting basal insulin and continuous glucose monitoring (CGM). After 26 weeks, participants were provided the option to continue in an extension phase through 52 weeks in which TI was used by both treatment groups. Results: In the TI group (N = 80), mean HbA1c was 8.1 ± 0.8% at the start of the RCT, 8.2 ± 1.2% at 26 weeks, and 8.6 ± 1.2% at 52 weeks (mean change from 26 to 52 weeks = 0.38%, 95% confidence interval [95% CI] 0.08%–0.67%, P = 0.003). In the RAA Crossover group (N = 88), mean HbA1c was 8.1 ± 1.1% at TI initiation (RCT week 26) and 8.4 ± 1.4% at 52 weeks (mean change = 0.31%, 95% CI −0.02%–0.64%, P = 0.08). There were no serious or unexpected pulmonary-related adverse events. The change in mean percent predicted forced expiratory volume in 1 s from the start of TI to 4 weeks after discontinuation was −0.5 (95% CI −1.9–0.9, P = 0.52) when combining the entire periods of TI exposure for both groups. CGM-measured time < 54 mg/dL was very low during TI use (TI group: 0.39 ± 0.61%; RAA Crossover group: 0.45 ± 0.59%). Conclusions: The INHALE-1 extension phase showed no safety concerns. Although HbA1c levels deteriorated slightly during the study, in view of the safety profile and increased patient satisfaction in the RCT portion of the trial, TI may be a useful treatment option for some pediatric patients with diabetes, particularly for those who choose not to or are unable to use an AID system.