Afrezza With Basal Combination (ABC): Afrezza® Combined With AID Pump or Insulin Degludec in Adults With Type 1 Diabetes (ABC)

ABC [Afrezza With Basal Combination]: A Phase 4 Study of Mealtime Control With Afrezza in Adult Subjects With Type 1 Diabetes Mellitus in Combination With an Automated Insulin Pump or Insulin Degludec

A phase 4 study evaluating the efficacy of mealtime control with Afrezza in combination with an automated insulin pump or insulin degludec in adult subjects with type 1 diabetes

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Biological: Afrezza (insulin human) Inhalation Powder; Device: Continuous Subcutaneous Insulin Infusion (CSII) pump with Automatic Insulin Delivery (AID); Biological: insulin degludec

Detailed Description

MKC-TI-192 is a Phase 4, 90-day, randomized, three-arm, multicenter clinical trial evaluating the treatment paradigm and efficacy of Afrezza in controlling postprandial glucose in adult subjects (≥18 years of age) with Type 1 Diabetes Mellitus (T1DM). Subjects will be randomized to one of three treatment groups (two Afrezza groups and one control group):

• Afrezza + AID: Subjects in this group will use Afrezza for their bolus (mealtime) insulin and a continuous subcutaneous insulin infusion (CSII) pump with an automatic insulin delivery (AID) algorithm using rapid acting analogs (RAA) for their basal and correction insulin coverage.
• Afrezza + Insulin Degludec: Subjects in this group will use Afrezza for their bolus (mealtime and correction) insulin and insulin degludec for basal insulin coverage.
• AID Control: Subjects in this group will use a CSII pump with an AID algorithm using RAA for all bolus (mealtime and correction) and basal insulin coverage (control group).

The study is composed of up to 5 clinic visits (screening, 3 treatment visits, and an end-of-treatment visit) and 9 telephone visits.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Loma Linda, California, United States, 92354
      • Diabetes Treatment Center, Loma Linda University
  • Texas
    • Austin, Texas, United States, 78731
      • Texas Diabetes and Endocrinology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects ≥18 years of age at the time of signing the informed consent form
• Clinical diagnosis of Type 1 Diabetes
• HbA1c ≥7.0% and <11.0%
• Treatment with a CSII pump with an AID algorithm (Medtronic 670G/770G or Tandem Control IQ) for at least 3 months
• Ability to pay for their own RAA used in the insulin pump or injections, either through co-pay or self-pay, for the duration of the study
• Willingness to follow study procedures including discontinuing their insulin pump and transitioning to insulin degludec injections plus Afrezza

Exclusion Criteria:

• A recent history of asthma (defined as using any medications to treat within the last year), chronic obstructive pulmonary disease (COPD), or any other clinically important pulmonary disease (e.g., cystic fibrosis, bronchopulmonary dysplasia), or significant congenital or acquired cardiopulmonary disease
• History of serious complications of diabetes (e.g., active proliferative retinopathy or symptomatic autonomic neuropathy)
• History of hypersensitivity to insulin or any of the Afrezza excipients
• On dialysis
• Respiratory tract infection within 14 days before screening (subject may return 14 days after resolution of symptoms for rescreening)
• Exposure to any investigational drug in the past 30 days or an investigational device in the past 2 weeks
• Adrenal insufficiency, active use of steroids or planned steroid use
• Hypothyroidism not controlled, as defined by thyroid stimulating hormone (TSH) outside the upper limit of the reference range by >1.5 × in the last 6 months, according to the local laboratory reference range
• Hyperthyroidism not controlled, as defined by TSH below the normal reference range, according to the local laboratory
• 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, breast-feeding, 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 reported by the patient, within the last 180 days before screening
• An episode of diabetic ketoacidosis (DKA), as determined by the Investigator, requiring hospitalization within the last 180 days before screening
• Exposure to Afrezza in the 30 days before screening
• Abnormal TSH or creatinine levels above 2.0 mg/dL

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Afrezza + Automatic Insulin Delivery; Subjects in this group will use Afrezza for their bolus (mealtime) insulin and a CSII pump with an AID algorithm using RAA for their basal and correction insulin coverage.	Biological: Afrezza (insulin human) Inhalation Powder; Pharmaceutical form: powder Route of administration: inhalation; Other Names: Technosphere Insulin; Device: Continuous Subcutaneous Insulin Infusion (CSII) pump with Automatic Insulin Delivery (AID); Acceptable AID systems in this study are Medtronic 670G/770G and Tandem Control IQ
Experimental: Afrezza + Insulin Degludec; Subjects in this group will use Afrezza for their bolus (mealtime and correction) insulin and insulin degludec for basal insulin coverage.	Biological: Afrezza (insulin human) Inhalation Powder; Pharmaceutical form: powder Route of administration: inhalation; Other Names: Technosphere Insulin; Biological: insulin degludec; Pharmaceutical form: solution for injection Route of administration: subcutaneous; Other Names: Tresiba
Active Comparator: AID Control; Subjects in this group will use a CSII pump with an AID algorithm using RAA for all bolus (mealtime and correction) and basal insulin coverage (control group).	Device: Continuous Subcutaneous Insulin Infusion (CSII) pump with Automatic Insulin Delivery (AID); Acceptable AID systems in this study are Medtronic 670G/770G and Tandem Control IQ

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c	Change in glycated hemoglobin (HbA1c) from baseline to end of study	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Events of Level 1 Hypoglycemia (SMBG < 70mg/dL)	Events of hypoglycemia (SMBG <70 mg/dL for SMBG values more than 30 minutes apart)	90 days
Events of Level 2 Hypoglycemia (SMBG < 54 mg/dL)	Events of hypoglycemia (SMBG <54 mg/dL for SMBG values more than 30 minutes apart)	90 days
Events of Severe Hypoglycemia	Events of severe hypoglycemia requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions	90 days
Change in Time in Range (Glucose of 70 - 180 mg/dL)	Change from baseline to end of study in Time in Range (TIR), defined as the percentage of time spent with glucose in the range of 70 to 180 mg/dL, based on continuous glucose monitoring derived glucose values	baseline and 90 days
Change in Time Below Range (Glucose <70 mg/dL)	Change from baseline to end of study in Time Below Range (TBR), defined as the percentage of time spent with glucose <70 mg/dL, based on continuous glucose monitoring derived glucose values	baseline and 90 days
Change in Percentage of Time With Glucose <54 mg/dL	Change from baseline to end of study in percentage of time spent with glucose <54 mg/dL, based on continuous glucose monitoring derived glucose values	baseline and 90 days
Change in Time Above Range (Glucose >180 mg/dL)	Change from baseline to end of study in Time Above Range (TAR), defined as the percentage of time spent with glucose >180 mg/dL, based on continuous glucose monitoring derived glucose values	baseline and 90 days
Change in Percentage of Time With Glucose >250 mg/dL	Change from baseline to end of study in percentage of time spent with glucose >250 mg/dL, based on continuous glucose monitoring derived glucose values	baseline and 90 days
Change in Coefficient of Variation (CV)	Change from baseline to end of study in glycemic variability as measured by coefficient of variation (CV), based on continuous glucose monitoring derived glucose values	baseline and 90 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Percent Predicted Forced Expiratory Volume in 1 Second	Change in percent predicted forced expiratory volume in 1 second (FEV1) from baseline to end of study	baseline and 90 days
Total Number of Treatment-Emergent Adverse Events	Total Number of Treatment-Emergent Adverse Events (TEAEs)	90 days
Total Number of Serious Adverse Events	Total Number of Serious Adverse Events (SAEs)	90 days
Total Number of Adverse Events of Special Interest	Total Number of Adverse Events of Special Interest (AESIs)	90 days
Total Number of Device Complaints	Total Number of Device Complaints	90 days

Collaborators and Investigators

• Sponsor: Mannkind Corporation
• Investigators: Study Director: Kevin Kaiserman, MD, Mannkind Corporation

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2022
• Primary Completion (Actual): October 17, 2022
• Study Completion (Actual): October 17, 2022

Study Registration Dates

• First Submitted: February 7, 2022
• First Submitted That Met QC Criteria: February 7, 2022
• First Posted (Actual): February 17, 2022

Study Record Updates

• Last Update Posted (Actual): April 8, 2025
• Last Update Submitted That Met QC Criteria: March 20, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Insulin; Diabetes Mellitus; Afrezza; Inhaled Insulin; Technosphere Insulin
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Diabetes Mellitus, Type 1; Physiological Effects of Drugs; Hypoglycemic Agents; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: MKC-TI-192

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No