Afrezza Safety and Pharmacokinetics Study in Pediatric Patients
Condition: Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Intervention: Afrezza
Intervention description: Pharmaceutical form: powder
Route of administration: inhalation
Intervention MeSH terms: Insulin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 4 Years
Maximum age: 17 Years
Healthy volunteers: No

Summary:

      Primary Objective:

      -To assess the safety and tolerability of Afrezza in children ages 4 to 17 years with type 1
      diabetes mellitus (T1DM).

      Secondary Objectives:

        -  To assess the ability to titrate the prandial and supplemental doses of Afrezza at each
           meal.

        -  To assess pharmacokinetics (PK) following a prandial dose of Afrezza in children ages 4
           to 17 years with T1DM.
    

Eligibility criteria:

        Inclusion criteria :

          1. Written or oral assent from the pediatric subject and written informed consent from
             the parent(s) or legal guardian and a witness, as required by both state and federal
             laws and the local Institutional Review Board;

          2. Children aged ≥4 and ≤17 years (enrolled sequentially into 3 age cohorts: 13 to 17, 8
             to 12, and 4 to 7 years);

          3. Clinical diagnosis of T1DM and using insulin for at least 1 year;

          4. Currently receiving a regimen of basal/bolus insulin administered by MDI for at least
             6 weeks prior to enrollment;

          5. Subjects with pre-breakfast self monitored blood glucose values between 80 and 250
             mg/dL for 5 of 7 documented daily readings obtained in the week prior to Visit 2
             (readings to be taken using glucometer provided at Screening Visit 1) and reported via
             the e Diary;

          6. Subjects on a regimen of insulin via continuous SC insulin infusion may be enrolled if
             they satisfy all other enrollment criteria and are willing to convert to MDI for the
             duration of the study, beginning 6 weeks prior to enrollment. They must continue to
             meet all enrollment criteria after converting to the MDI regimen;

          7. Total daily insulin dose ≤1.5 units/kg/day with a minimum of 3 units of RAA at every
             meal.

          8. Hemoglobin A1c (HbA1c) ≥7.0% to <10.0% at the time of screening;

          9. Fasting serum C-peptide ≤0.3 ng/mL;

         10. Forced expiratory volume in 1 second (FEV1) ≥70% of National Health and Nutrition
             Examination Survey (NHANES) III predicted for children ≥8 years of age or Wang
             predicted for children <8 years of age;

         11. Forced vital capacity ≥70% of NHANES III predicted for children ≥8 years of age or
             Wang predicted for children <8 years of age;

         12. Females of childbearing potential, must use "highly effective" methods of
             contraception throughout conduct of the trial

        Exclusion criteria:

          1. Body mass index below 25th or above 95th percentile for age and gender according to
             Centers for Disease Control and Prevention growth charts;

          2. History of physician diagnosis of asthma or any other clinically important pulmonary
             disease, or use of any medications to treat such conditions within the last year;

          3. Allergy or known hypersensitivity for AFREZZA or to drugs with similar chemical
             structure;

          4. Unstable diabetes control, defined as 2 or more episodes of severe hypoglycemia (i.e.,
             an episode associated with a seizure, coma, or loss of consciousness) or any
             hospitalization or emergency room visit for poor diabetes control, ketoacidosis,
             hypoglycemia, or hyperglycemia within the preceding 3 months from screening;

          5. Serum creatinine ≥ the upper limit of normal for age;

          6. Respiratory tract infection within 30 days before screening or between screening and
             initiation of treatment period; subject may return 4 weeks after resolution of the
             infection for rescreening;

          7. Evidence of any complication of diabetes (proliferative retinopathy, autonomic
             neuropathy, nephropathy, etc), or likelihood of requiring laser photocoagulation,
             vitrectomy, or other specific treatment for diabetic retinopathy in the coming year;

          8. Smoking of tobacco or other substances or positive urine cotinine testing (>100
             ng/mL);

          9. Positive urine drug screen;

         10. Positive urine pregnancy test for female subjects of childbearing potential;

         11. Inability to perform study procedures including pulmonary function testing;

         12. Exposure to any investigational product(s) in the past 3 months or 5 half-lives,
             whichever is more;

         13. History of eating disorder;

         14. Any disease or exposure to any medication which, in the judgment of the principal
             Investigator, may impact glucose metabolism;

         15. Any concurrent medical or major psychiatric condition that makes the subject
             unsuitable for the clinical study or impairs the subject's ability to participate in
             the study.

        The above information is not intended to contain all considerations relevant to a patient's
        potential participation in a clinical trial.