Dataset Information

Comprehensive Pulmonary Safety Review of Inhaled Technosphere^® Insulin in Patients with Diabetes Mellitus.

ABSTRACT:

Background and objective

Technosphere^® Insulin (TI), a human insulin powder for inhalation (Afrezza^®; MannKind Corporation, Westlake Village, CA, USA), is an ultra-rapid-acting inhaled insulin indicated to improve postprandial glycemic control in patients with type 1 or type 2 diabetes mellitus (T1DM or T2DM). Because TI is absorbed across the alveolar membrane, the objective of this analysis was to characterize its pulmonary safety.

Methods

Pooled data from 13 phase 2/3 clinical studies in 5505 patients with T1DM or T2DM treated with TI, Technosphere inhalation powder without insulin (TP; placebo), or active-comparator treatment were analyzed for incidences of respiratory treatment-emergent adverse events (TEAEs), changes in pulmonary function, and lung malignancies. Radiographic changes in the lungs were monitored in a subset of 229 patients.

Results

Among 3017 patients receiving TI, the median duration of TI exposure was 168 days; median active-comparator and TP exposure durations were 363 and 149 days for 2198 and 290 patients, respectively. Respiratory TEAEs were comparable across treatments, except for a higher incidence of mild cough with TI in active-comparator studies (28.0% vs. 5.2%). Slight reversible declines in pulmonary function from baseline were observed for TI versus TP and active-comparator treatments, including in a subpopulation of patients with retrospectively identified lung dysfunction. Lung malignancies were reported in two patients on active TI therapy with a smoking history. No clinically significant changes from baseline were observed in radiographic images.

Conclusions

Pulmonary safety assessment of the TI inhalation system did not identify any safety issues in individuals with either T1DM or T2DM.

SUBMITTER: McGill JB

PROVIDER: S-EPMC7511468 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Publications

Comprehensive Pulmonary Safety Review of Inhaled Technosphere<sup>®</sup> Insulin in Patients with Diabetes Mellitus.

McGill Janet B JB Peters Anne A Buse John B JB Steiner Susanne S Tran Tiffany T Pompilio Frank M FM Kendall David M DM

Clinical drug investigation 20201001 10

<h4>Background and objective</h4>Technosphere<sup>®</sup> Insulin (TI), a human insulin powder for inhalation (Afrezza<sup>®</sup>; MannKind Corporation, Westlake Village, CA, USA), is an ultra-rapid-acting inhaled insulin indicated to improve postprandial glycemic control in patients with type 1 or type 2 diabetes mellitus (T1DM or T2DM). Because TI is absorbed across the alveolar membrane, the objective of this analysis was to characterize its pulmonary safety.<h4>Methods</h4>Pooled data from ...[more]

PMID: 32720187

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Project description:BackgroundThe majority of therapies have generally targeted fasting glucose control, and current mealtime insulin therapies have longer time action profiles than that of endogenously secreted insulin. The primary purpose of this study was to assess both glucose time-in-range (TIR: 70-180 mg/dL) and postprandial glucose excursions (PPGE) in 1-4 h using a real-time continuous glucose monitor (CGM) with Technosphere insulin (TI) versus insulin aspart in patients with type 1 diabetes (T1DM) on multiple daily injections (MDI).Research design and methodsThis pilot, investigator-led, collaborative, open-label, multicenter, clinical research trial enrolled 60 patients with T1DM with HbA1c levels ≥6.5% and ≤10%. Individuals were randomized to treatment with titrated TI (n = 26) or titrated insulin aspart (n = 34), stratified by baseline HbA1c levels (≤8% or >8%). All were required to wear a real-time CGM throughout the trial. All patients in the TI group were advised to take supplemental inhalations at 1 and 2 h after meals if indicated based on postprandial glucose (PPG) values. The coprimary outcomes were assessed both in the full intent-to-treat population and in those individuals randomized to TI who were compliant with supplemental doses ≥90% of the time (n = 15). The CGM data were analyzed using linear regression models.ResultsOverall, those treated with TI versus aspart achieved comparable TIR, but less time spent in hypoglycemia (<60 and <50 mg/dL, both P < 0.05). In the TI-compliant group (n = 15), TIR was significantly greater (62.5% ± 2.6% vs. 53.8% ± 1.7%, P = 0.009) and time in hyperglycemia >180 mg/dL was lower (34.2% ± 2.7% vs. 41.0% ± 1.7%, P = 0.045) as compared with the aspart group. PPG was also significantly lower in the TI cohort at 60 and 90 min postmeal, and PPGE were lower in the TI-compliant group as compared with the aspart group over 1-4-h postmeal (P < 0.05). In addition, there was weight gain in the aspart group compared with weight loss in the TI group (P = 0.006) despite higher prandial TI insulin dose.ConclusionsWe conclude that using TI appropriately at mealtimes with supplemental dosing improves prandial glucose (TIR and 1-4 h) control without any increase in time in hypoglycemia or weight gain in patients with T1DM on MDI. The study results support a larger study using a treat-to-target design to confirm these findings. Clinical trial reg. no. NCT03143816, clinicaltrials.gov .

Dataset Information

Comprehensive Pulmonary Safety Review of Inhaled Technosphere^® Insulin in Patients with Diabetes Mellitus.

Background and objective

Methods

Results

Conclusions

Publications

Comprehensive Pulmonary Safety Review of Inhaled Technosphere<sup>®</sup> Insulin in Patients with Diabetes Mellitus.

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Dataset Information

Comprehensive Pulmonary Safety Review of Inhaled Technosphere® Insulin in Patients with Diabetes Mellitus.

Background and objective

Methods

Results

Conclusions

Publications

Comprehensive Pulmonary Safety Review of Inhaled Technosphere<sup>®</sup> Insulin in Patients with Diabetes Mellitus.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Comprehensive Pulmonary Safety Review of Inhaled Technosphere^® Insulin in Patients with Diabetes Mellitus.