Afrezza Safety and Pharmacokinetics Study in Pediatric Patients

Open-label, Single-arm, Multiple-dose Safety, Titration, and Pharmacokinetic Trial of Afrezza® in Pediatric Patients Ages 4 to 17 Years With Type 1 Diabetes Mellitus

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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Biological: Afrezza

Detailed Description

The patients are expected to participate in the study for approximately 6 to 8 weeks from Screening to final follow-up visit.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Barbara Davis Center for Childhood Diabetes
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University Hospital
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Tampa, Florida, United States, 33612
      • USF Diabetes Center
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Atlanta Diabetes Associates
    • Atlanta, Georgia, United States, 30318
      • Van Meter Pediatric Endocrinology, P.C.
    • Atlanta, Georgia, United States, 30322
      • Emory University Children's Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University, Riley Hospital for Children
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • Barry J. Reiner, MD, LLC
  • Nevada
    • Las Vegas, Nevada, United States, 89113
      • Diabetes, Obesity, Cardiovascular Clinical Specialists (DOCS)
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • Le Bonheur Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Afrezza (Technosphere Insulin); Individualized dose of Afrezza (Technosphere Insulin) for each patient at each meal (breakfast, lunch, and dinner) for 30 days. During the trial, all patients will receive multiple injections of basal long acting insulin, in general at bedtime every day.	Biological: Afrezza; Pharmaceutical form: powder Route of administration: inhalation; Other Names: Technosphere Insulin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin Maximum Observed Concentration (Cmax)	Insulin Cmax after a dose of Afrezza	250 minutes post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin Time to Reach Cmax (Tmax)	Insulin Tmax after a dose of Afrezza	250 minutes post-dose
Insulin Area Under Concentration Time Curve (AUC)	Insulin AUC after a dose of Afrezza	250 minutes post-dose
Assessment of Fumaryl Diketopiperazine (FDKP) Elimination Half-life (t1/2)	FDKP (inert carrier excipient) calculated half life t1/2	Using PK data collected over 250 minutes post-dose of Afrezza

Collaborators and Investigators

• Sponsor: Mannkind Corporation
• Investigators: Study Director: Clinical Operations, Mannkind Corporation

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 28, 2017
• Primary Completion (ACTUAL): March 17, 2020
• Study Completion (ACTUAL): June 25, 2020

Study Registration Dates

• First Submitted: August 17, 2015
• First Submitted That Met QC Criteria: August 17, 2015
• First Posted (ESTIMATE): August 18, 2015

Study Record Updates

• Last Update Posted (ACTUAL): April 6, 2021
• Last Update Submitted That Met QC Criteria: March 11, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: MKC-TI-155 Part 1; U1111-1166-5528 (OTHER: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No