AzTrials
AzTrials

Diabetes Mellitus, Type 1Phase 4NCT05904743

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

A Phase 4 study testing Afrezza, insulin degludec and Rapid-acting Insulin Analog in people with Diabetes Mellitus, Type 1, run by Mannkind Corporation at 19 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Diabetes Mellitus, Type 1
What is being tested?
Afrezza, insulin degludec and Rapid-acting Insulin Analog
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
141 participants
Where
19 sitesUnited States
Study dates
7 Jul 2023to 24 Jun 2024
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
  • Current (at time of screening) rapid-acting insulin analog (RAA) in use for at least 4 weeks
  • If AID system used, automated insulin delivery must be active >85% of the time in the 4 weeks prior to screening
Show all 16Show fewer
  • 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
  • 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.

Who cannot join

  • 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
Show all 14Show fewer
  • 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

Trial locations and contacts

19 sites in 1 country.

19 sites in 1 country

United States19 sites

  • Atlanta Diabetes Associates

    Atlanta, Georgia, 30318

  • Barbara Davis Center

    Aurora, Colorado, 80045

  • Texas Diabetes & Endocrinology, P.A.

    Austin, Texas, 78731

  • Boston Medical Center

    Boston, Massachusetts, 02118

  • Joslin Diabetes Center

    Boston, Massachusetts, 02215

  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27514

  • Northwestern University Division of Endocrinology, Metabolism and Molecular Medicine

    Chicago, Illinois, 60611

  • The University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • Las Vegas Endocrinology

    Henderson, Nevada, 89074

  • Loma Linda University-Diabetes Treatment Center

    Loma Linda, California, 92354

  • Endocrine Associate of West Village, PC

    Long Island City, New York, 11106

  • Mount Sinai Diabetes Center

    New York, New York, 10075

  • Mountain State Diabetes

    Parkersburg, West Virginia, 26101

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Diabetes and Glandular Disease Clinic, P.A.

    San Antonio, Texas, 78229

  • Sansum Diabetes Research

    Santa Barbara, California, 93105

  • University of Washington Diabetes Institute

    Seattle, Washington, 98119

  • SUNY Upstate Medical University

    Syracuse, New York, 13210

  • Iowa Diabetes Research

    West Des Moines, Iowa, 50265

Other trials in United States

About this study

Official title: INHALE-3: A 17-Week Randomized Trial and a 13-Week Extension, Evaluating the Efficacy and Safety of Inhaled Insulin (Afrezza) Combined With Insulin Degludec Versus Usual Care in Adults With Type 1 Diabetes

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.

Being tested
Afrezza, insulin degludec, Rapid-acting Insulin Analog, Basal Insulin
Keywords
Diabetes Mellitus, Insulin, Inhaled, Afrezza, Technosphere, Adults, Degludec, Glucose sensors, Insulin pumps, CGM
Medical subject headings
Diabetes Mellitus, Type 1, Diabetes Mellitus, Insulin Resistance, Respiratory Aspiration

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AfrezzaBiological

    Also called Technosphere Insulin

    Pharmaceutical form: powder Route of administration: inhalation

  • insulin degludecBiological

    Pharmaceutical form: solution for injection Route of administration: subcutaneous

  • Rapid-acting Insulin AnalogBiological

    Also called any FDA approved Rapid-acting Insulin Analog

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

  • Basal InsulinBiological

    Also called any FDA approved Basal Insulin

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

Study groups in NCT05904743
Study groupRoleWhat they receive
Afrezza (Technosphere Insulin) + insulin degludecExperimentalThe 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.
Receives: Biological: Afrezza; Biological: insulin degludec
Usual Care: Insulin delivery with either MDI, a pump without automation, or an AID system and CGMActive comparatorThe 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.
Receives: Biological: Rapid-acting Insulin Analog; Biological: Basal Insulin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in glycated hemoglobin (HbA1c)

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

    Measured: 17 weeks

Secondary outcomes (37)

  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%)

    Measured: 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%)

    Measured: 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

    Measured: 17 weeks

  4. Mean Continuous Glucose Monitoring (CGM) glucose

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

    Measured: 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

    Measured: 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

    Measured: 17 weeks

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

    HbA1c from baseline to 17 weeks, for superiority assessment

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 17 weeks

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

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

    Measured: 17 weeks

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

    HbA1c <7.0% at 17 weeks

    Measured: 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%

    Measured: 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%

    Measured: 17 weeks

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

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

    Measured: 17 weeks

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

    Percent time with glucose >300 mg/dL

    Measured: 17 weeks

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

    CGM-measured prolonged hyperglycemia events

    Measured: 17 weeks

  18. Continuous Glucose Monitoring (CGM) measured hypoglycemia events

    CGM-measured hypoglycemia events

    Measured: 17 weeks

  19. Standard Deviation (SD) of glucose

    SD of glucose

    Measured: 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)

    Measured: 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

    Measured: 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%

    Measured: 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%

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 30 weeks

  29. Other serious adverse events, including hospitalizations

    Other serious adverse events, including hospitalizations

    Measured: 30 weeks

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

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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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)

    Measured: 30 weeks

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

    Hyperglycemic events from logged BGM measurements

    Measured: 30 weeks

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

    CGM-measured prolonged hyperglycemia events

    Measured: 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)

    Measured: 30 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Jun 2023
  2. Study start7 Jul 2023
  3. Primary completion26 Mar 2024
  4. Study completion24 Jun 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
141 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05904743
Sponsor's protocol ID
MKC-TI-193
Status last verified
Aug 2024
First submitted
2 Jun 2023
Last updated
9 Aug 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Afrezza, insulin degludec and Rapid-acting Insulin Analog in people with Diabetes Mellitus, Type 1, run by Mannkind Corporation at 19 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in glycated hemoglobin (HbA1c) (time frame: 17 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05904743.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in