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Afrezza Safety and Pharmacokinetics Study in Pediatric Patients

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ClinicalTrials.gov Identifier: NCT02527265
Recruitment Status : Recruiting
First Posted : August 18, 2015
Last Update Posted : December 6, 2017
Sponsor:
Information provided by (Responsible Party):

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.

Patients who completed 4 weeks of Afrezza treatment and have shown to be safe and well controlled with Afrezza + basal insulin will have the option to continue the extension treatment up to 1 year.


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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1
U.S. FDA Resources

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, with an optional extension up to a year.

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: Up to 13 months ]
    Comparison of baseline to week 6 and week 52


Eligibility Criteria

Information from the National Library of Medicine

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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02527265


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

Locations
United States, Colorado
Investigational Site 637 Not yet recruiting
Aurora, Colorado, United States, 80045
United States, Connecticut
Investigational Site 635 Not yet recruiting
New Haven, Connecticut, United States, 06510
United States, Florida
Investigational Site 636 Not yet recruiting
Gainesville, Florida, United States, 32610
United States, Georgia
Investigational Site 002 Recruiting
Atlanta, Georgia, United States, 30318
Investigational Site 639 Recruiting
Atlanta, Georgia, United States, 30318
Investigational Site 642 Not yet recruiting
Atlanta, Georgia, United States, 30322
United States, Maryland
Investigational Site 638 Recruiting
Baltimore, Maryland, United States, 21229
United States, Pennsylvania
Investigational Site 640 Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Investigational Site 641 Not yet 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    Key Record Dates
Last Update Posted: December 6, 2017
Last Verified: December 2017
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, Globin Zinc
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs