Afrezza® INHALE-1 Study in Pediatrics

INHALE-1 is a Phase 3, open-label, randomized clinical study evaluating the efficacy and safety of Afrezza in combination with a basal insulin (i.e., the Afrezza group) versus insulin aspart, insulin lispro or insulin glulisine in combination with a basal insulin (i.e., the Rapid-acting Insulin Analog \[RAA\] injection group) in pediatric subjects with type 1 or type 2 diabetes mellitus. Following 26 weeks of randomized treatment (i.e., Afrezza or RAA injection combined with a basal insulin), all subjects will enter a treatment extension where subjects will receive Afrezza until Week 52. The purpose of the treatment extension is to assess safety and efficacy with continued use of Afrezza.

Pediatric subjects ≥4 and \<18 years of age will be enrolled in this study. Subjects will be randomly assigned in a 1:1 ratio to either the Afrezza group or the RAA injection group.

The study is composed of:

* Up to 5-week screening/run-in period
* 26 week randomized treatment period
* 26-week treatment extension
* 4-week follow-up period


Eligibility Criteria:
Inclusion Criteria:

* Assent from the pediatric subject, as appropriate, and fully informed consent from the parent(s) or legal guardian, as required by both state and federal laws and the local Institutional Review Board (IRB)
* Subjects ≥4 and \<18 years of age
* Clinical diagnosis of type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) per the Investigator and have been using insulin for at least 6 months for T1DM, or at least 3 months for T2DM
* Treatment with basal-bolus insulin therapy delivered by multiple daily injections for at least 2 weeks
* Bolus insulins are restricted to the RAAs insulin lispro, insulin aspart or insulin glulisine, including biosimilar products
* Basal insulins are restricted to insulin glargine, insulin degludec or insulin detemir, including biosimilar products
* Access to stable WiFi connection
* HbA1c ≥7.0% and ≤11%
* Average prandial dose of insulin ≥2 units per meal
* Utilized CGM for ≥70% of the time over a consecutive 14-day period preceding randomization

Exclusion Criteria:

* History of recent blood transfusions (within previous 3 months), hemoglobinopathies, or any other conditions that affect HbA1c measurements
* Recent history of asthma (defined as using any medications to treat within the last year), any other clinically important pulmonary disease (e.g., cystic fibrosis or bronchopulmonary dysplasia), or significant congenital or acquired cardiopulmonary disease
* History of serious complications of diabetes (e.g., active proliferative retinopathy or symptomatic autonomic neuropathy), or likely need for specific treatment for diabetic retinopathy (laser photocoagulation, vitrectomy, other) in the next year
* FEV1 and FEV1/forced vital capacity (FVC) ≤80% of predicted Global Lung Function Initiative (GLI) value
* Inability to achieve an acceptable FEV1 and FVC reading for subjects ≥8 years of age would make the subject ineligible
* For subjects \<8 years of age who are unable to achieve an acceptable FVC reading, FEV1 only may be assessed; inability to achieve an acceptable FEV1 would make the subject ineligible
* Respiratory tract infection within 14 days before screening (subject may return 14 days after resolution of symptoms for rescreening)
* Inability or unwillingness to perform study procedures
* Exposure to any investigational product(s), including drugs or devices, in the past 30 days
* Any disease other than diabetes or exposure to any medication that, in the judgment of the Investigator, may impact glucose metabolism and current or anticipated acute uses of glucocorticoids or weight loss medications, with the exception of metformin and/or GLP-1 agonists (if GLP-1 agonists used for at least the 3 months prior to enrollment) in subjects with T2DM
* Use of antiadrenergic drugs (e.g., clonidine)
* Any concurrent illness (other than diabetes mellitus) not controlled by a stable therapeutic regimen
* Current uncontrolled eating disorder (e.g., anorexia or bulimia nervosa)
* Current drug or alcohol abuse or a history of drug or alcohol abuse that, in the opinion of the Investigator or the Sponsor, would make the subject an unsuitable candidate for participation in the study
* Smoking (includes cigarettes, cigars, pipes, marijuana, and vaping devices) for the preceding 6 months and/or positive urine cotinine test
* Female subject who is pregnant, breast-feeding, intends to become pregnant, or is of child-bearing potential, sexually active and not using adequate contraceptive methods as required by local regulation or practice
* An event of severe hypoglycemia, as judged by the Investigator, within the last 90 days prior to screening
* An episode of DKA requiring hospitalization within the last 90 days prior to screening