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CompletedNCT05904743Updated Aug 9, 2024

INHALE-3: Afrezza® Combined With Insulin Degludec Versus Usual Care in Adults With Type 1 Diabetes

A Phase 4 interventional study of Afrezza and insulin degludec in Diabetes Mellitus, Type 1, sponsored by Mannkind Corporation. Completed at 19 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-08-09.

Sponsored by Mannkind Corporation · Phase 4, Interventional, and Treatment

From the registry’s dates

  • Primary completion was Mar 2024, 2 years 6 months ago, and no results have been posted to the registry.
Phase
Phase 4
Study type
Interventional
Enrollment
141
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

INHALE-3 is a Phase 4, randomized controlled trial (RCT) that will randomly assign participants ≥18 years of age with type 1 diabetes (T1D) using multiple daily injections (MDI), an automated insulin delivery (AID) system, or a pump without automation, and continuous glucose monitoring (CGM) 1:1 to an insulin regimen of insulin degludec plus inhaled insulin (Afrezza) and CGM or continuation of usual care. The primary outcome of the RCT is at 17 weeks. The RCT will be followed by a 13-week extension phase in which participants in both groups will use the degludec-inhaled insulin regimen.

02

Conditions studied

  • Diabetes Mellitus, Type 1

Keywords

  • Diabetes Mellitus
  • Insulin
  • Inhaled
  • Afrezza
  • Technosphere
  • Adults
  • Degludec
  • Glucose sensors
  • Insulin pumps
  • CGM
03

In context

Diabetes Mellitus

10,925 studies on the registry are indexed under Diabetes Mellitus; 1,319 are open to participants now.

This study's enrollment of 141 is above the median of 80 across 8,367 interventional studies indexed under Diabetes Mellitus.

Browse Diabetes Mellitus studies →

Lead sponsor

Mannkind Corporation is the lead sponsor of 55 studies on the registry; 3 are open to participants now.

Of its 8 completed or terminated interventional studies of FDA-regulated products, 3 (38%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Ability to provide informed consent for study participation
  • Clinical diagnosis of T1D (per the Investigator)
  • Treatment with insulin for at least 6 months prior to the collection of the baseline continuous glucose monitoring (CGM) data

  • Same treatment regimen (MDI, an AID system, or an insulin pump without automation) for the 3 months prior to screening

    1. Current (at time of screening) rapid-acting insulin analog (RAA) in use for at least 4 weeks
    2. If AID system used, automated insulin delivery must be active >85% of the time in the 4 weeks prior to screening
    3. If MDI used, participant must be using a long-acting basal insulin plus injecting a RAA bolus for meals, per Investigator
  • Total daily insulin dose 20-100 units
  • Age ≥ 18 years
  • HbA1c \<11.0%
  • Participant uses real-time CGM (any type of real-time CGM) on a regular basis (at least 70% of the time in the 4 weeks prior to screening)
  • No use of inhaled insulin in the 3 months prior to screening
  • If female of childbearing potential, willing and able to have pregnancy testing
  • Investigator believes that the participant can safely use the study treatment and will follow protocol

  • No medical, psychiatric,or other conditions, or medications being taken that in the Investigator's judgement would be a safety concern for participation in the study

    1. This includes considering the potential impact of medical conditions known to be present including cardiovascular, liver, kidney disease, thyroid disease, adrenal disease, malignancies, vision difficulties, active proliferative retinopathy, and other medical conditions; psychiatric conditions including eating disorders; drug or alcohol abuse.

Exclusion criteria

Exclusion Criteria:

  • History of recent blood transfusions (within previous 3 months prior to randomization), hemoglobinopathies, (sickle cell trait is not an exclusion), or any other conditions that affect HbA1c measurements
  • 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 or bronchopulmonary dysplasia), or significant congenital or acquired cardiopulmonary disease as judged by the Investigator
  • Exposure to any investigational product(s), including drugs or devices, in the 90 days prior to the start of screening
  • Any disease other than diabetes or current use (or anticipated use during the study) of any medication that, in the judgment of the Investigator, may impact glucose metabolism
  • Current or anticipated acute uses of oral, inhaled or injectable glucocorticoids during the time period of the trial (topical glucocorticoid use is acceptable)
  • Use of a non-insulin glucose-lowering medication within 3 months prior to signing informed consent
  • Smoking (includes cigarettes, cigars, pipes, marijuana, and vaping devices) within 3 months prior to screening
  • Pregnant or lactating, planning to become pregnant during the study, or is a woman of childbearing potential and not on an acceptable form of birth control (acceptable includes abstinence, condoms, oral/injectable contraceptives, IUD, or implant); childbearing means that menstruation has started, and the participant is not surgically sterile or greater than 12 months post-menopausal
  • No known stage 4/5 renal failure or on dialysis
  • Taking Hydroxyurea medication
  • An event of severe hypoglycemia, as judged by the Investigator, within the last 90 days prior to screening
  • An episode of diabetic ketoacidosis (DKA) diagnosed at a health care facility within the 90 days prior to screening or severe hypoglycemia event within the 90 days prior to screening
  • Employed by, or having immediate family members employed by MannKind Corporation or JAEB Center for Health Research, or having a direct supervisor at place of employment who is also directly involved in conducting the clinical trial (as Study Investigator, coordinator, etc.); or having a first-degree relative who is directly involved in in conducting the clinical trial
  • Have a history or current diagnosis of lung cancer
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
141 participants (actual)

Study arms

  • Experimental
    Afrezza (Technosphere Insulin) + insulin degludec

    The Afrezza-Degludec group will inhale Afrezza at meals and corrections and will inject insulin degludec once a day for the 17 weeks of the RCT Phase. Dexcom Continuous Glucose Monitoring (CGM) will be provided. The Afrezza-Degludec group will continue to use Afrezza and insulin degludec for an additional 13 weeks in the Extension Phase.

    Biological: Afrezza · Biological: insulin degludec

  • Active comparator
    Usual Care: Insulin delivery with either MDI, a pump without automation, or an AID system and CGM

    The Usual Care group will continue to receive insulin as they did before the study. This could be by multiple daily injections (MDI) or by using an insulin pump with or without automation for the 17 weeks of the randomized controlled trial (RCT) Phase. Participants will continue to use their personal continuous glucose monitor (CGM) as they did before the study. The Usual Care group will then use Afrezza and insulin degludec for 13 weeks in the Extension Phase. Dexcom CGM will be provided during the Extension Phase.

    Biological: Rapid-acting Insulin Analog · Biological: Basal Insulin

Interventions

  • BiologicalAfrezza

    Pharmaceutical form: powder Route of administration: inhalation

    Also known as: Technosphere Insulin

  • Biologicalinsulin degludec

    Pharmaceutical form: solution for injection Route of administration: subcutaneous

  • BiologicalRapid-acting Insulin Analog

    Pharmaceutical form: clear and colorless solution for injection Route of administration: subcutaneous

    Also known as: any FDA approved Rapid-acting Insulin Analog

  • BiologicalBasal Insulin

    Pharmaceutical form: clear and colorless solution for injection Route of administration: subcutaneous

    Also known as: any FDA approved Basal Insulin

06

What researchers measure

Primary outcomes

  1. Change in glycated hemoglobin (HbA1c)

    Change in HbA1c from baseline to 17 weeks (non-inferiority margin 0.4%)

    Time frame: 17 weeks

Secondary outcomes

  1. Continuous Glucose Monitoring (CGM) measured percent time with glucose less than 54 mg/dL

    CGM-measured percent time with glucose \<54 mg/dL from baseline to 17 weeks (non-inferiority, margin 0.5%)

    Time frame: 17 weeks

  2. Continuous Glucose Monitoring (CGM) measured percent time with glucose less than 70 mg/dL

    CGM-measured percent time with glucose \<70mg/dL from baseline to 17 weeks (non-inferiority, margin 2.0%)

    Time frame: 17 weeks

  3. Continuous Glucose Monitoring (CGM) measured daytime (0600-midnight) percent time in range with glucose 70-180 mg/dL

    CGM-measured daytime (0600-midnight) percent time in range with glucose 70-180 mg/dL from baseline to 17 weeks, for superiority assessment

    Time frame: 17 weeks

  4. Mean Continuous Glucose Monitoring (CGM) glucose

    Mean CGM glucose from baseline to 17 weeks, for superiority assessment

    Time frame: 17 weeks

  5. Continuous Glucose Monitoring (CGM) measured (24-hours) percent time in range (TIR) with glucose 70-180 mg/dL

    CGM-measured (24-hours) percent time in range with glucose 70-180 mg/dL from baseline to 17 weeks, for superiority assessment

    Time frame: 17 weeks

  6. Continuous Glucose Monitoring (CGM) measured percent time with glucose greater than 180 mg/dL

    CGM-measured percent time with glucose \> 180 mg/dL from baseline to 17 weeks, for superiority assessment

    Time frame: 17 weeks

  7. Change in glycated hemoglobin (HbA1c) for superiority assessment

    HbA1c from baseline to 17 weeks, for superiority assessment

    Time frame: 17 weeks

  8. Continuous Glucose Monitoring (CGM) measured time with glucose greater than 250 mg/dL

    CGM-measured time with glucose \>250 mg/dL from baseline to 17 weeks, for superiority assessment

    Time frame: 17 weeks

  9. Continuous Glucose Monitoring (CGM) measured time with glucose less than 70 mg/dL

    CGM-measured time with glucose \<70 mg/dL from baseline to 17 weeks, for superiority assessment

    Time frame: 17 weeks

  10. Continuous Glucose Monitoring (CGM) measured time with glucose less than 54 mg/dL

    CGM-measured time with glucose \<54 mg/dL from baseline to 17 weeks, for superiority assessment

    Time frame: 17 weeks

  11. Continuous Glucose Monitoring (CGM) measured coefficient of variation

    CGM-measured coefficient of variation from baseline to 17 weeks, for superiority assessment

    Time frame: 17 weeks

  12. Change in HbA1c less than 7.0% at 17 weeks

    HbA1c \<7.0% at 17 weeks

    Time frame: 17 weeks

  13. Change in HbA1c from baseline to 17 weeks, with an improvement of greater than 0.5%

    HbA1c improvement from baseline to 17 weeks \>0.5%

    Time frame: 17 weeks

  14. Change in HbA1c from baseline to 17 weeks, with an improvement of greater than 1.0%

    HbA1c improvement from baseline to 17 weeks \>1.0%

    Time frame: 17 weeks

  15. Percent time in range (TIR) with glucose 70-140 mg/dL

    Percent time in range with glucose 70-140 mg/dL

    Time frame: 17 weeks

  16. Percent time with glucose greater than 300 mg/dL

    Percent time with glucose \>300 mg/dL

    Time frame: 17 weeks

  17. Continuous Glucose Monitoring (CGM) measured prolonged hyperglycemia events

    CGM-measured prolonged hyperglycemia events

    Time frame: 17 weeks

  18. Continuous Glucose Monitoring (CGM) measured hypoglycemia events

    CGM-measured hypoglycemia events

    Time frame: 17 weeks

  19. Standard Deviation (SD) of glucose

    SD of glucose

    Time frame: 17 weeks

  20. "Fasting glucose" by Continuous Glucose Monitoring (CGM)

    "Fasting glucose" by CGM (defined as closest value to 6 a.m.; assumed, but not verified, with no food during the prior 4-hour period)

    Time frame: 17 weeks

  21. Percent time in range (TIR) with glucose 70-180 mg/dL greater than 70%

    Percent time in range with glucose 70-180 mg/dL \>70% at 17 weeks

    Time frame: 17 weeks

  22. Percent time in range (TIR) with glucose 70-180 mg/dL improvement from baseline to 17 weeks greater than or equal to 5%

    Percent time in range with glucose 70-180 mg/dL improvement from baseline to 17 weeks ≥5%

    Time frame: 17 weeks

  23. Percent time in range (TIR) with glucose 70-180 mg/dL improvement from baseline to 17 weeks ≥10%

    Percent time in range with glucose 70-180 mg/dL improvement from baseline to 17 weeks ≥10%

    Time frame: 17 weeks

  24. Percent time with glucose less than 70 mg/dL less than 4%

    Percent time with glucose \<70 mg/dL \<4% at 17 weeks

    Time frame: 17 weeks

  25. Percent time with glucose less than 54 mg/dL less than1%

    Percent time with glucose \<54 mg/dL \<1% at 17 weeks

    Time frame: 17 weeks

  26. Percent time in range (TIR) 70-180 mg/dL greater than 70% and time less than 54 mg/dL less than 1%

    Percent time in range 70-180 mg/dL \>70% and time \<54 mg/dL \<1% at 17 weeks

    Time frame: 17 weeks

  27. Incidence of severe hypoglycemia events

    Incidence of severe hypoclycemia events, defined as events requiring assistance of another person due to cognitive impairment to actively administer carbohydrate, glucagon, or other resuscitative actions

    Time frame: 30 weeks

  28. Continuous Glucose Monitoring (CGM) measured percent time with glucose less than 54 mg/dL

    CGM-measured percent time with glucose less than 54 mg/dL

    Time frame: 30 weeks

  29. Other serious adverse events, including hospitalizations

    Other serious adverse events, including hospitalizations

    Time frame: 30 weeks

  30. Incidence and severity of treatment-emergent adverse events (TEAEs)

    Incidence and severity of treatment-emergent adverse events (TEAEs)

    Time frame: 30 weeks

  31. Incidence and severity of adverse events of special interest (AESIs) as well as the number of participants with AESIs and number of individual events

    Incidence and severity of adverse events of special interest (AESIs) as well as the number of participants with AESIs and number of individual events

    Time frame: 30 weeks

  32. Change from baseline to 17 weeks in Forced Expiratory Volume in one second (FEV1)

    Change from baseline to 17 weeks in FEV1

    Time frame: 17 weeks

  33. Proportion of participants with Forced Expiratory Volume in one second (FEV1) reduction greater than or equal to 20%

    Proportions of participants in each group who have experienced ≥20% reduction in FEV1 from baseline to Week 17

    Time frame: 30 weeks

  34. Hypoglycemic events from logged blood glucose measurements (BGM): Level 1 events (less than 70 mg/dL) and Level 2 events (less than 54 mg/dL) separately

    Hypoglycemic events from logged BGM measurements: Level 1 events (\<70 mg/dL) and Level 2 events (\<54 mg/dL)

    Time frame: 30 weeks

  35. Hyperglycemic events from logged blood glucose measurements (BGM)

    Hyperglycemic events from logged BGM measurements

    Time frame: 30 weeks

  36. Continuous Glucose Monitoring (CGM) measured prolonged hyperglycemia events

    CGM-measured prolonged hyperglycemia events

    Time frame: 30 weeks

  37. Continuous Glucose Monitoring (CGM) measured hypoglycemia events (both a safety and efficacy endpoint)

    CGM-measured hypoglycemia events (both a safety and efficacy endpoint)

    Time frame: 30 weeks

Other outcomes

  1. Weight

    Weight

    Time frame: 17 weeks

  2. Post prandial glucose for first meal challenge

    Post prandial glucose for first meal challenge

    Time frame: 17 weeks

  3. Area under the curve (AUC) for first meal challenge

    Area under the curve (AUC) for first meal challenge

    Time frame: 17 weeks

  4. Patient-reported outcome (PRO) questionnaires

    Type 1 Diabetes Distress Scale (T1-DDS): 28-item validated survey pertaining to distress symptoms related to diabetes (recorded from a scale of 1 to 6). Hypoglycemia Confidence Scale (HCS): 9-item validated survey pertaining to situations where hypoglycemia could occur and queries about the participant's level of confidence in those situations (recorded from a scale 1 to 4). Insulin Treatment Satisfaction Questionnaire (ITSQ): 22-item survey with a 5-factor structure assessing insulin satisfaction (scores range from 0 to 100). Freedom and Flexibility: 6-item non-validated survey pertaining to life experiences impacted by having diabetes (scores range from 6 to 36) Insulin Adherence: 1-item non-validated survey pertaining to number of missed boluses in the past week

    Time frame: 17 weeks

  5. Change in HbA1c from baseline to 17 weeks, with a worsening of greater than 0.5%

    Additional binary HbA1c endpoints, HbA1c worsening from baseline to 17 weeks \>0.5%

    Time frame: 17 weeks

  6. Change in HbA1c from baseline to 17 weeks, with a worsening of greater than 1.0%

    Additional binary HbA1c endpoints, HbA1c worsening from baseline to 17 weeks \>1.0%

    Time frame: 17 weeks

  7. Percent time in range (TIR) with glucose 70-180 mg/dL worsening from baseline to 17 weeks greater than or equal to 5%

    Additional binary CGM endpoints, Percent time in range with glucose 70-180 mg/dL worsening from baseline to 17 weeks ≥5%

    Time frame: 17 weeks

  8. Percent time in range (TIR) with glucose 70-180 mg/dL worsening from baseline to 17 weeks greater than or equal to 10%

    Additional binary CGM endpoints, Percent time in range with glucose 70-180 mg/dL worsening from baseline to 17 weeks ≥10%

    Time frame: 17 weeks

07

Study locations

19 sites
  • Loma Linda University-Diabetes Treatment Center
    Loma Linda, California 92354, United States
  • Sansum Diabetes Research
    Santa Barbara, California 93105, United States
  • Barbara Davis Center
    Aurora, Colorado 80045, United States
  • Atlanta Diabetes Associates
    Atlanta, Georgia 30318, United States
  • Northwestern University Division of Endocrinology, Metabolism and Molecular Medicine
    Chicago, Illinois 60611, United States
  • Iowa Diabetes Research
    West Des Moines, Iowa 50265, United States
  • Boston Medical Center
    Boston, Massachusetts 02118, United States
  • Joslin Diabetes Center
    Boston, Massachusetts 02215, United States
  • Mayo Clinic
    Rochester, Minnesota 55905, United States
  • Las Vegas Endocrinology
    Henderson, Nevada 89074, United States
  • Endocrine Associate of West Village, PC
    Long Island City, New York 11106, United States
  • Mount Sinai Diabetes Center
    New York, New York 10075, United States
  • SUNY Upstate Medical University
    Syracuse, New York 13210, United States
  • University of North Carolina at Chapel Hill
    Chapel Hill, North Carolina 27514, United States
  • Texas Diabetes & Endocrinology, P.A.
    Austin, Texas 78731, United States
  • The University of Texas Southwestern Medical Center
    Dallas, Texas 75390, United States
  • Diabetes and Glandular Disease Clinic, P.A.
    San Antonio, Texas 78229, United States
  • University of Washington Diabetes Institute
    Seattle, Washington 98119, United States
  • Mountain State Diabetes
    Parkersburg, West Virginia 26101, United States
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 9, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT05904743
Lead sponsor
Mannkind Corporation
Collaborators
Jaeb Center for Health Research
Responsible party
Sponsor
First posted
Jun 15, 2023
Start date
Jul 7, 2023
Primary completion
Mar 26, 2024
Completion
Jun 24, 2024
Last update
Aug 9, 2024

Study contacts

Kevin Kaiserman, MD
study director · Mannkind Corporation
Irl B. Hirsch, MD
study chair · University of Washington

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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