Afrezza With Basal Combination

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Type 1 Diabetes

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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Afrezza + Automatic Insulin Delivery<br>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<br>* Pharmaceutical form: powder Route of administration: inhalation<br>* Other names: Technosphere Insulin;Device: Continuous Subcutaneous Insulin Infusion (CSII) pump with Automatic Insulin Delivery (AID)<br>* Acceptable AID systems in this study are Medtronic 670G/770G and Tandem Control IQ<br>|
| Experimental: Afrezza + Insulin Degludec<br>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<br>* Pharmaceutical form: powder Route of administration: inhalation<br>* Other names: Technosphere Insulin;Biological: insulin degludec<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous<br>* Other names: Tresiba;|
| Active Comparator: AID Control<br>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)<br>* Acceptable AID systems in this study are Medtronic 670G/770G and Tandem Control IQ<br>|

What is the study measuring?
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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 |
| --- | --- | --- |
| Rate of Level 1 Hypoglycemic Events | Event rate of hypoglycemia (SMBG <70 mg/dL) | 90 days | 
| Rate of Level 2 Hypoglycemic Events | Event rate of hypoglycemia (SMBG <54 mg/dL) | 90 days | 
| Rate of Severe Hypoglycemic Events | Event rate of severe hypoglycemia requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions | 90 days | 
| Change in Time in Range (70 - 180 mg/dL) | Change in percent time in range (TIR) based on continuous glucose monitoring derived glucose values | 90 days | 
| Change in Time Below Range (glucose <70 mg/dL) | Change in percent time below range (TBR), defined as time spent with glucose <70 mg/dL based on continuous glucose monitoring derived glucose values | 90 days | 
| Change in Percent Time with Glucose <54 mg/dL | Change in percent time spent with glucose <54 mg/dL based on continuous glucose monitoring derived glucose values | 90 days | 
| Change in Time Above Range (glucose >180 mg/dL) | Change in percent time above range (TAR), defined as time spent with glucose >180 mg/dL based on continuous glucose monitoring derived glucose values | 90 days | 
| Change in Percent Time with Glucose >250 mg/dL | Change in percent time spent with glucose >250 mg/dL based on continuous glucose monitoring derived glucose values | 90 days | 
| Change in Coefficient of variation (CV) | Change in glycemic variability as measured by coefficient of variation (CV) based on continuous glucose monitoring derived glucose values | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus, Insulin, Inhaled Insulin, Afrezza, Technosphere Insulin