Afrezza Safety and Pharmacokinetics Study in Pediatric Patients

• ClinicalTrials.gov Identifier: NCT02527265
• Recruitment Status: Recruiting
• First Posted: August 18, 2015
• Last Update Posted: March 8, 2019
• Sponsor: Mannkind Corporation
• Information provided by (Responsible Party): Mannkind Corporation

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Type 1 Diabetes Mellitus	Drug: Afrezza	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 46 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: September 28, 2017
• Estimated Primary Completion Date: July 2020
• Estimated Study Completion Date: January 2021

Arms and Interventions

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.	Drug: Afrezza; Pharmaceutical form: powder Route of administration: inhalation; Other Name: Technosphere Insulin

Outcome Measures

Primary Outcome Measures :

1. Number of patients with adverse events [ Time Frame: Baseline to week 6 ]
   Number and percentage of patients with any TEAE, any serious TEAE, any severe TEAE, any TEAE leading to treatment discontinuation, or any TEAE leading to death (only if any occurred) will be summarized by age cohort
2. Number of patients with hypoglycemic events [ Time Frame: Baseline to week 6 ]
   Hypoglycemia, defined as blood glucose <= 70 mg/dL or in absence of blood glucose, symptoms that are resolved by the administration of carbohydrates.

Secondary Outcome Measures :

1. insulin maximum observed concentration (Cmax) [ Time Frame: 1 day ]
   PK measures for Afrezza Inhalation Powder as measured by Cmax - timepoints: -30, -25, -15, 0, 5, 10, 15, 18, 20, 30, 45, 55, 60, 90, 120, 125, 180, 240, 245, 250 minutes post dosing
2. insulin time to reach Cmax (tmax) [ Time Frame: 1 day ]
   PK measures for Afrezza Inhalation Powder as measured by tmax - timepoints: -30, -25, -15, 0, 5, 10, 15, 18, 20, 30, 45, 55, 60, 90, 120, 125, 180, 240, 245, 250 minutes post dosing
3. insulin area under concentration time curve (AUC) [ Time Frame: 1 day ]
   PK measures for Afrezza Inhalation Powder as measured by AUC - timepoints: -30, -25, -15, 0, 5, 10, 15, 18, 20, 30, 45, 55, 60, 90, 120, 125, 180, 240, 245, 250 minutes post dosing
4. Assessment of fumaryl diketopiperazine (FDKP) elimination half-life (t1/2) [ Time Frame: 1 day ]
   PK measures for FDKP as measured by t1/2 - timepoints: -30, -25, -15, 0, 5, 10, 15, 18, 20, 30, 45, 55, 60, 90, 120, 125, 180, 240, 245, 250 minutes post dosing
5. Number of patients adhered to dose titration rules [ Time Frame: 30 days ]
   Doses for each of 3 days' meals will be titrated based on the median SMBG (120 to 150 minutes post-dose)
6. Measurement of anti-insulin antibodies [ Time Frame: Baseline to week 6 ]
   Comparison of baseline to week 6

Eligibility Criteria

• Ages Eligible for Study: 4 Years to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: For site information, call or email; 877-298-4186; mapp@mannkindcorp.com

Locations

United States, Colorado

Investigational Site 637; Recruiting

Aurora, Colorado, United States, 80045

United States, Connecticut

Investigational Site 635; Recruiting

New Haven, Connecticut, United States, 06510

United States, Florida

Investigational Site 636; Recruiting

Gainesville, Florida, United States, 32610

Investigational Site 643; Recruiting

Tampa, Florida, United States, 33612

United States, Georgia

Investigational Site 002; Recruiting

Atlanta, Georgia, United States, 30318

Investigational Site 639; Recruiting

Atlanta, Georgia, United States, 30318

Investigational Site 642; Recruiting

Atlanta, Georgia, United States, 30322

United States, Maryland

Investigational Site 638; Recruiting

Baltimore, Maryland, United States, 21229

United States, Nevada

Investigational Site 646; Recruiting

Las Vegas, Nevada, United States, 89113

United States, Pennsylvania

Investigational Site 640; Recruiting

Philadelphia, Pennsylvania, United States, 19104

United States, Tennessee

Investigational Site 641; Recruiting

Memphis, Tennessee, United States, 38105

Sponsors and Collaborators

Mannkind Corporation

Investigators

• Study Director: Clinical Operations; Mannkind Corporation

More Information

• Responsible Party: Mannkind Corporation
• ClinicalTrials.gov Identifier: NCT02527265 History of Changes
• Other Study ID Numbers: MKC-TI-155; U1111-1166-5528 ( Other Identifier: UTN )
• First Posted: August 18, 2015
• Last Update Posted: March 8, 2019
• Last Verified: March 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Insulin; Insulin, Globin Zinc; Hypoglycemic Agents; Physiological Effects of Drugs