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

Phase 4

Completed

Conditions: Type 1 Diabetes

Interventions: Biological: Afrezza (insulin human) Inhalation Powder
Device: Continuous Subcutaneous Insulin Infusion (CSII) pump with Automatic Insulin Delivery (AID)
Biological: insulin degludec

Registration Number: NCT05243628

Lead Sponsor: Mannkind Corporation

Brief Summary: 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

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 33

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Afrezza + Insulin Degludec	Afrezza (insulin human) Inhalation Powder	Subjects in this group will use Afrezza for their bolus (mealtime and correction) insulin and insulin degludec for basal insulin coverage.
AID Control	Continuous Subcutaneous Insulin Infusion (CSII) pump with Automatic Insulin Delivery (AID)	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).
Afrezza + Automatic Insulin Delivery	Continuous Subcutaneous Insulin Infusion (CSII) pump with Automatic Insulin Delivery (AID)	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.
Afrezza + Automatic Insulin Delivery	Afrezza (insulin human) Inhalation Powder	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.
Afrezza + Insulin Degludec	insulin degludec	Subjects in this group will use Afrezza for their bolus (mealtime and correction) insulin and insulin degludec for basal insulin coverage.

Primary Outcome Measures

Name	Time	Method
Change in HbA1c	90 days	Change in glycated hemoglobin (HbA1c) from baseline to end of study

Secondary Outcome Measures

Name	Time	Method
Change in Percentage of Time With Glucose <54 mg/dL	baseline and 90 days	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
Events of Level 1 Hypoglycemia (SMBG < 70mg/dL)	90 days	Events of hypoglycemia (SMBG \<70 mg/dL for SMBG values more than 30 minutes apart)
Events of Level 2 Hypoglycemia (SMBG < 54 mg/dL)	90 days	Events of hypoglycemia (SMBG \<54 mg/dL for SMBG values more than 30 minutes apart)
Events of Severe Hypoglycemia	90 days	Events of severe hypoglycemia requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions
Change in Time in Range (Glucose of 70 - 180 mg/dL)	baseline and 90 days	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
Change in Time Below Range (Glucose <70 mg/dL)	baseline and 90 days	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
Change in Time Above Range (Glucose >180 mg/dL)	baseline and 90 days	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
Change in Percentage of Time With Glucose >250 mg/dL	baseline and 90 days	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
Change in Coefficient of Variation (CV)	baseline and 90 days	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

Trial Locations

Locations (2): Diabetes Treatment Center, Loma Linda University
🇺🇸
Loma Linda, California, United States
Texas Diabetes and Endocrinology
🇺🇸
Austin, Texas, United States
Diabetes Treatment Center, Loma Linda University
🇺🇸Loma Linda, California, United States