Afrezza Safety and Pharmacokinetics Study in Pediatric Patients

Type 1 Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02527265
• Other study ID #: MKC-TI-155 Part 1
• Secondary ID: U1111-1166-5528
• Status: Completed
• Phase: Phase 2
• Start date: September 28, 2017
• Est. completion date: June 25, 2020

Study information

• Verified date: March 2021
• Source: Mannkind Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: June 25, 2020
• Est. primary completion date: March 17, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

Biological:
• Afrezza
Pharmaceutical form: powder Route of administration: inhalation

Locations

Country	Name	City	State
United States	Atlanta Diabetes Associates	Atlanta	Georgia
United States	Emory University Children's Center	Atlanta	Georgia
United States	Van Meter Pediatric Endocrinology, P.C.	Atlanta	Georgia
United States	Barbara Davis Center for Childhood Diabetes	Aurora	Colorado
United States	Barry J. Reiner, MD, LLC	Baltimore	Maryland
United States	University of Florida	Gainesville	Florida
United States	Indiana University, Riley Hospital for Children	Indianapolis	Indiana
United States	Diabetes, Obesity, Cardiovascular Clinical Specialists (DOCS)	Las Vegas	Nevada
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Le Bonheur Children's Hospital	Memphis	Tennessee
United States	Yale University Hospital	New Haven	Connecticut
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	USF Diabetes Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Mannkind Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin Maximum Observed Concentration (Cmax)	Insulin Cmax after a dose of Afrezza	250 minutes post-dose
Secondary	Insulin Time to Reach Cmax (Tmax)	Insulin Tmax after a dose of Afrezza	250 minutes post-dose
Secondary	Insulin Area Under Concentration Time Curve (AUC)	Insulin AUC after a dose of Afrezza	250 minutes post-dose
Secondary	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