Afrezza Safety and Pharmacokinetics Study in Pediatric Patients

NCT ID: NCT02527265

Last Updated: 2021-04-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-28
• Study Completion Date: 2020-06-25

Brief 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.

Detailed Description

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

Conditions

Type 1 Diabetes Mellitus

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Afrezza

Intervention Type: BIOLOGICAL

Pharmaceutical form: powder

Route of administration: inhalation

Interventions

Afrezza

Pharmaceutical form: powder

Route of administration: inhalation

Intervention Type: BIOLOGICAL

Other Intervention Names

Technosphere Insulin

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.

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mannkind Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Operations

Role: STUDY_DIRECTOR

Mannkind Corporation

Locations

Children's Hospital Los Angeles

Los Angeles, California, United States

Barbara Davis Center for Childhood Diabetes

Aurora, Colorado, United States

Yale University Hospital

New Haven, Connecticut, United States

University of Florida

Gainesville, Florida, United States

USF Diabetes Center

Tampa, Florida, United States

Atlanta Diabetes Associates

Atlanta, Georgia, United States

Van Meter Pediatric Endocrinology, P.C.

Atlanta, Georgia, United States

Emory University Children's Center

Atlanta, Georgia, United States

Indiana University, Riley Hospital for Children

Indianapolis, Indiana, United States

Barry J. Reiner, MD, LLC

Baltimore, Maryland, United States

Diabetes, Obesity, Cardiovascular Clinical Specialists (DOCS)

Las Vegas, Nevada, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Le Bonheur Children's Hospital

Memphis, Tennessee, United States

Countries

United States

References

Haller MJ, Jones MC, Bhavsar S, Kaiserman KB. Time-Action Profile of Technosphere Insulin in Children with Type 1 Diabetes. Diabetes Ther. 2023 Mar;14(3):611-617. doi: 10.1007/s13300-023-01368-7. Epub 2023 Jan 18.

Reference Type: DERIVED

PMID: 36652106 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1166-5528

Identifier Type: OTHER

Identifier Source: secondary_id

MKC-TI-155 Part 1

Identifier Type: -

Identifier Source: org_study_id