Afrezza® Dosing Optimization Study

NCT04849845 | Completed Phase 4 Results FDA Drug FDA Device

• 1 other identifier: MKC-TI-191
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

MKC-TI-191 is a Phase 4, single-arm, multicenter, proof-of-concept clinical trial evaluating the efficacy and safety of Afrezza, administered according to the current Afrezza prescribing information (PI) compared to a titrated dose, in combination with a basal insulin in adult subjects (≥18 years of age) with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). Eligible subjects will be on a stable regimen consisting of a basal bolus insulin therapy prior to screening. The study is composed of up to 4 clinic visits (screening, 2 treatment visits, and a follow-up visit). Two individual doses of Afrezza will be administered during a meal challenge at Visits 2 and 3. The duration of each subject's participation in the trial is expected to be approximately 2 weeks.

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2

Keywords

Afrezza; Dosing; Technosphere; Inhaled; Insulin; Diabetes

Outcome Measures

Primary Outcomes (1)

• Post-prandial Glucose Excursion

  Mean glucose change from baseline (or postprandial glucose excursion \[PPGE\]) based on self-monitored blood glucose (SMBG) at 15, 30, 45, 60, 90 and 120 minutes after the dose of Afrezza with baseline defined as SMBG at the time of the dose of Afrezza (t=0)

  120 minutes post-dose

Secondary Outcomes (6)

• Number of Subjects With at Least 1 Event of Level 1 Hypoglycemia

  120 minutes

• Percent of Level 1 Hypoglycemia

  120 minutes

• Number of Subjects With at Least 1 Event of Level 2 Hypoglycemia

  120 minutes

• Percent of Level 2 Hypoglycemia

  120 minutes

• Number of Subjects With At Least 1 Event of Severe Hypoglycemia

  120 minutes

Study Arms (1)

Afrezza

EXPERIMENTAL

The test product is defined as Afrezza \[insulin human\] inhalation powder administered using the Afrezza inhaler. In addition, subjects will take their personal basal insulin while enrolled in the study.

Combination Product: Afrezza Dose 1; Combination Product: Afrezza Dose 2

Interventions

Afrezza Dose 1 COMBINATION_PRODUCT

The first dose of Afrezza will be based on the dose of subcutaneous rapid-acting analogue (RAA) insulin that the subject would normally take for the standardized meal, converted according to the guidelines provided in the current Afrezza U.S. prescribing information.

Afrezza

Afrezza Dose 2 COMBINATION_PRODUCT

The second dose of Afrezza will be based on the dose of subcutaneous rapid-acting analogue that the subject would normally take for the standardized meal, converted by multiplying their RAA dose by 2 and rounding down to the nearest Afrezza cartridge size.

Afrezza

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects ≥18 years of age at the time of signing the informed consent form
• Clinical diagnosis of T1DM or T2DM (per the Investigator) and on a stable basal-bolus insulin regimen

You may not qualify if:

• History of asthma, chronic obstructive pulmonary disease, or any other clinically important pulmonary disease (e.g., cystic fibrosis, bronchopulmonary dysplasia), use of any medications to treat such conditions within the last year, or significant congenital or acquired cardiopulmonary disease
• History of serious complications of diabetes (e.g., active proliferative retinopathy or symptomatic autonomic neuropathy)
• On dialysis
• Respiratory tract infection within 14 days before screening (subject may return 14 days after resolution of symptoms for rescreening)
• Treatment with any investigational drug in the past 30 days or an investigational device in the past 2 weeks
• Any disease other than diabetes or initiation of any new medication that, in the judgment of the Investigator, could have a direct impact on glycemic control during the study
• Use of antiadrenergic drugs (e.g., beta blockers and clonidine)
• Any concurrent illness (other than diabetes mellitus) not controlled by a stable therapeutic regimen
• History of a significant eating disorder (e.g., anorexia or bulimia nervosa)
• Current drug or alcohol abuse or a history of drug or alcohol abuse that, in the opinion of the Investigator or the Sponsor, would make the subject an unsuitable candidate for participation in the study
• History of smoking (includes cigarettes, cigars, pipes, vaping devices, and marijuana) in the 6 months before screening
• Female subject who is pregnant, breastfeeding, intends to become pregnant, or is of child-bearing potential and not using adequate contraceptive methods as required by local regulation or practice (may include sexual abstinence)
• An event of severe hypoglycemia, as judged by the Investigator, within the 90 days before screening
• An episode of diabetic ketoacidosis (DKA) requiring hospitalization within the 90 days before screening
• Exposure to Afrezza in the 30 days before screening

Sponsors & Collaborators

• Mannkind Corporation: lead

Study Sites (2)

AMCR Institute

Escondido, California, 92025, United States

Location

Diablo Clinical Research

Walnut Creek, California, 94598, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Insulin Resistance; Respiratory Aspiration; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Hyperinsulinism; Respiration Disorders; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

DOS had no planned or conducted hypothesis testing, and no alpha adjustment was made to account for multiple testing of exploratory endpoints. Instead, DOS aimed to be a small-scale test of the higher dose suggested by previous studies and clinical experience. With no formal hypothesis testing, descriptive statistical comparisons are used to assess the efficacy and safety outcomes of the higher dose for purposes of generating hypothesis for a larger study.

Results Point of Contact

• Title: Johanna Ulloa
• Organization: MannKind Corporation

contact@mannkindcorp.com

818-661-5000

Study Officials

• Kevin Kaiserman, MD

  Mannkind Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2021
• First Posted: April 19, 2021
• Study Start: April 9, 2021
• Primary Completion: May 28, 2021
• Study Completion: May 28, 2021
• Last Updated: September 18, 2023
• Results First Posted: September 18, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)