Long-Term Nonclinical Pulmonary Safety Assessment of Afrezza, a Novel Insulin Inhalation Powder
| Autor: | Jack A. Reynolds, Kevin McInally, Dominic Poulin, Kristen J. Nikula, Stephanie F Greene |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Pathology
medicine.medical_specialty medicine.medical_treatment 030209 endocrinology & metabolism Inhalation Toxicology Toxicology 030226 pharmacology & pharmacy Pathology and Forensic Medicine 03 medical and health sciences Dogs 0302 clinical medicine Administration Inhalation Animals Humans Hypoglycemic Agents Insulin Medicine Lung Molecular Biology Inhalation business.industry Inhaler Cell Biology Hyperplasia medicine.disease Mucus Rats medicine.anatomical_structure Diabetes Mellitus Type 2 Histopathology Powders business Respiratory tract |
| Zdroj: | Toxicologic Pathology. 49:334-348 |
| ISSN: | 1533-1601 0192-6233 |
| Popis: | Afrezza delivers inhaled insulin using the Gen2 inhaler for the treatment of patients with type 1 and type 2 Diabetes. Afrezza was evaluated in long-term nonclinical pulmonary safety studies in 2 toxicology species. Chronic inhalation toxicology studies in rat (26 weeks) and dog (39 weeks) and an inhalation carcinogenicity study in rats were conducted with Technosphere insulin (Afrezza) and with Technosphere alone as a vehicle control. Respiratory tract tissues were evaluated by histopathology and cells expressing proliferating cell nuclear antigen (PCNA) were quantified in lungs of rats. Microscopic findings in rats exposed to Afrezza were attributed to the Technosphere particle component, were confined to nasal epithelia, and consisted of eosinophilic globules and nasal epithelial degeneration. There were no Afrezza-related changes in pulmonary PCNA labeling indices in alveoli, large bronchioles, or terminal bronchioles. Microscopic findings in rats exposed to Technosphere particles included eosinophilic globules, mucus cell hyperplasia, and epithelial degeneration in the nasal cavities. PCNA labeling indices were increased in large bronchioles and terminal bronchioles but not in alveoli. There were no Technosphere particle-related findings in the dog study. Afrezza did not exhibit carcinogenic potential in the 2-year study in rats. These nonclinical inhalation studies support the use of Afrezza in humans over extended periods. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|