Diabetes Mellitus, Type 1Phase 4DOSNCT04849845
Afrezza® Dosing Optimization Study
A Phase 4 study testing Afrezza Dose 1 and Afrezza Dose 2 in people with Diabetes Mellitus, Type 1 and Diabetes Mellitus, Type 2, run by Mannkind Corporation at 2 sites in United States.
Trial summary
MKC-TI-191 is a Phase 4, single-arm, multicenter, proof-of-concept clinical trial evaluating the efficacy and safety of Afrezza, administered according to the current Afrezza prescribing information (PI) compared to a titrated dose, in combination with a basal insulin in adult subjects (≥18 years of age) with type 1… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2
- What is being tested?
- Afrezza Dose 1 and Afrezza Dose 2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesUnited States
- Study dates
- 9 Apr 2021to 28 May 2021
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Subjects ≥18 years of age at the time of signing the informed consent form
- Clinical diagnosis of T1DM or T2DM (per the Investigator) and on a stable basal-bolus insulin regimen
Who cannot join
- History of asthma, chronic obstructive pulmonary disease, or any other clinically important pulmonary disease (e.g., cystic fibrosis, bronchopulmonary dysplasia), use of any medications to treat such conditions within the last year, or significant congenital or acquired cardiopulmonary disease
- History of serious complications of diabetes (e.g., active proliferative retinopathy or symptomatic autonomic neuropathy)
- On dialysis
- Respiratory tract infection within 14 days before screening (subject may return 14 days after resolution of symptoms for rescreening)
- Treatment with any investigational drug in the past 30 days or an investigational device in the past 2 weeks
- Any disease other than diabetes or initiation of any new medication that, in the judgment of the Investigator, could have a direct impact on glycemic control during the study
Show all 15Show fewer
- 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, breastfeeding, 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 judged by the Investigator, within the 90 days before screening
- An episode of diabetic ketoacidosis (DKA) requiring hospitalization within the 90 days before screening
- Exposure to Afrezza in the 30 days before screening
Trial locations and contacts
2 sites in 1 country.
United States2 sites
AMCR Institute
Escondido, California, 92025
Diablo Clinical Research
Walnut Creek, California, 94598
About this study
Official title: DOS [Dosing Optimization Study]: Open-label, Single-arm, Proof-of-Concept Dosing Study of Afrezza® in Adult Subjects 18 Years and Older With Type 1 or Type 2 Diabetes Mellitus
MKC-TI-191 is a Phase 4, single-arm, multicenter, proof-of-concept clinical trial evaluating the efficacy and safety of Afrezza, administered according to the current Afrezza prescribing information (PI) compared to a titrated dose, in combination with a basal insulin in adult subjects (≥18 years of age) with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). Eligible subjects will be on a stable regimen consisting of a basal bolus insulin therapy prior to screening. The study is composed of up to 4 clinic visits (screening, 2 treatment visits, and a follow-up visit). Two individual doses of Afrezza will be administered during a meal challenge at Visits 2 and 3. The duration of each subject's participation in the trial is expected to be approximately 2 weeks.
Read the detailed description
Screening (Visit 1): Informed consent and California Experimental Subjects Bill of Rights will be signed and eligibility confirmed. Eligible subjects will be enrolled at Visit 1.
Subjects will come into the clinic in a fasting state for a meal challenge and individual dose of Afrezza during Visits 2 and 3. At the beginning of each visit, before their dose of Afrezza, subjects will have FEV1 measurements taken in the clinic. Each meal challenge will consist of 1 to 2 bottles of nutritional shake to be fully consumed within 15 minutes. The nutritional shake will contain approximately 240 calories, 41 g carbohydrate, 10 g protein, and 4 g fat per bottle. Each Afrezza dose will be administered at the start of the meal challenge.
Visit 2: The first dose of Afrezza will be based on the dose of subcutaneous (SC) rapid-acting analogue (RAA) insulin that the subject would normally take, converted according to the guidelines provided in the current Afrezza prescribing information. If subject's normal RAA dose is <4 units or 5 units, subject will be asked to consume enough nutritional shake, per their normal I:C ratio, to cover an RAA dose of 4 units or ≥6 units such that their Afrezza dose at Visit 3 is higher than the dose taken at Visit 2. After completing the standardized meal challenge, the Investigator will decide, based on the subject's glucose excursion at Visit 2, if the subject should proceed to Visit 3 where a second dose of Afrezza will be administered.
Visit 3: The second dose of Afrezza will be based on the dose of SC RAA that the subject would normally take, converted by multiplying their RAA dose by 2 and rounding down to the nearest Afrezza cartridge size.
Follow-up Visit (Visit 4): Subjects will return for safety assessments, including a final FEV1 measurement, 24 to 72 hours after their last dose of Afrezza.
- Being tested
- Afrezza Dose 1, Afrezza Dose 2
- Keywords
- Afrezza, Dosing, Technosphere, Inhaled, Insulin, Diabetes
- Medical subject headings
- Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Insulin Resistance, Respiratory Aspiration, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Afrezza Dose 1Combination product
The first dose of Afrezza will be based on the dose of subcutaneous rapid-acting analogue (RAA) insulin that the subject would normally take for the standardized meal, converted according to the guidelines provided in the current Afrezza U.S. prescribing information.
Afrezza Dose 2Combination product
The second dose of Afrezza will be based on the dose of subcutaneous rapid-acting analogue that the subject would normally take for the standardized meal, converted by multiplying their RAA dose by 2 and rounding down to the nearest Afrezza cartridge size.
| Study group | Role | What they receive |
|---|---|---|
| Afrezza | Experimental | The test product is defined as Afrezza [insulin human] inhalation powder administered using the Afrezza inhaler. In addition, subjects will take their personal basal insulin while enrolled in the study. Receives: Combination Product: Afrezza Dose 1; Combination Product: Afrezza Dose 2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Post-prandial Glucose Excursion
Mean glucose change from baseline (or postprandial glucose excursion [PPGE]) based on self-monitored blood glucose (SMBG) at 15, 30, 45, 60, 90 and 120 minutes after the dose of Afrezza with baseline defined as SMBG at the time of the dose of Afrezza (t=0)
Measured: 120 minutes post-dose
Secondary outcomes (6)
Number of Subjects With at Least 1 Event of Level 1 Hypoglycemia
Number of subjects with at least 1 event (also referred to as incidence) of Level 1 hypoglycemia (<70mg/dL) within the 120 minutes after Afrezza dosing as confirmed by SMBG.
Measured: 120 minutes
Percent of Level 1 Hypoglycemia
Percent of total SMBG measurements <70 mg/dL (Level 1 hypoglycemia) within the 120 minutes after Afrezza dosing.
Measured: 120 minutes
Number of Subjects With at Least 1 Event of Level 2 Hypoglycemia
Number of subjects with at least 1 event (also referred to as incidence) of Level 2 hypoglycemia (<54mg/dL) within the 120 minutes after Afrezza dosing as confirmed by SMBG.
Measured: 120 minutes
Percent of Level 2 Hypoglycemia
Percent of total SMBG measurements <54 mg/dL (Level 2 hypoglycemia) within the 120 minutes after Afrezza dosing
Measured: 120 minutes
Number of Subjects With At Least 1 Event of Severe Hypoglycemia
Number of subjects with at least 1 event (also referred to as incidence) of severe hypoglycemia, defined as events requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions within the 120 minutes after Afrezza dosing.
Measured: 120 minutes
Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Between Two Points, Baseline and 120 Minutes Post-Afrezza Dose
Change in percent predicted forced expiratory volume in 1 second (FEV1) between two points (value at 120 minutes post-Afrezza dose minus value at baseline). Standard deviation was not reported.
Measured: 120 minutes post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2021
- Study start9 Apr 2021
- Primary completion28 May 2021
- Study completion28 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Diabetes Mellitus, Type 1Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mannkind Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Kevin Kaiserman, MD, Study director, Mannkind Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04849845
- Sponsor's protocol ID
- MKC-TI-191
- Acronym
- DOS
- Status last verified
- Sep 2023
- First submitted
- 16 Apr 2021
- Last updated
- 18 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- DOS [Dosing Optimization Study]: Open-label, Single-arm, Proof-of-Concept Dosing Study of Afrezza® in Adult Subjects 18 Years and Older With Type 1 or Type 2 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT04849845
- Acronym / sponsor ID
- DOS / MKC-TI-191
- Keywords
- Afrezza, Dosing, Technosphere, Inhaled, Insulin, Diabetes
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Mannkind CorporationIndustry (pharma, biotech, devices)
- Study start
- 9 Apr 2021 (actual)
- Primary completion
- 28 May 2021 (actual)
- Study completion
- 28 May 2021 (actual)
- First posted
- 19 Apr 2021 (actual)
- Results
- Posted 18 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
MKC-TI-191 is a Phase 4, single-arm, multicenter, proof-of-concept clinical trial evaluating the efficacy and safety of Afrezza, administered according to the current Afrezza prescribing information (PI) compared to a titrated dose, in combination with a basal insulin in adult subjects (≥18 years of age) with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). Eligible subjects will be on a stable regimen consisting of a basal bolus insulin therapy prior to screening. The study is composed of up to 4 clinic visits (screening, 2 treatment visits, and a follow-up visit). Two individual doses of Afrezza will be administered during a meal challenge at Visits 2 and 3. The duration of each subject's participation in the trial is expected to be approximately 2 weeks.
Detailed description
Screening (Visit 1): Informed consent and California Experimental Subjects Bill of Rights will be signed and eligibility confirmed. Eligible subjects will be enrolled at Visit 1.
Subjects will come into the clinic in a fasting state for a meal challenge and individual dose of Afrezza during Visits 2 and 3. At the beginning of each visit, before their dose of Afrezza, subjects will have FEV1 measurements taken in the clinic. Each meal challenge will consist of 1 to 2 bottles of nutritional shake to be fully consumed within 15 minutes. The nutritional shake will contain approximately 240 calories, 41 g carbohydrate, 10 g protein, and 4 g fat per bottle. Each Afrezza dose will be administered at the start of the meal challenge.
Visit 2: The first dose of Afrezza will be based on the dose of subcutaneous (SC) rapid-acting analogue (RAA) insulin that the subject would normally take, converted according to the guidelines provided in the current Afrezza prescribing information. If subject's normal RAA dose is <4 units or 5 units, subject will be asked to consume enough nutritional shake, per their normal I:C ratio, to cover an RAA dose of 4 units or ≥6 units such that their Afrezza dose at Visit 3 is higher than the dose taken at Visit 2. After completing the standardized meal challenge, the Investigator will decide, based on the subject's glucose excursion at Visit 2, if the subject should proceed to Visit 3 where a second dose of Afrezza will be administered.
Visit 3: The second dose of Afrezza will be based on the dose of SC RAA that the subject would normally take, converted by multiplying their RAA dose by 2 and rounding down to the nearest Afrezza cartridge size.
Follow-up Visit (Visit 4): Subjects will return for safety assessments, including a final FEV1 measurement, 24 to 72 hours after their last dose of Afrezza.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Afrezza | Experimental | Combination Product: Afrezza Dose 1, Combination Product: Afrezza Dose 2The test product is defined as Afrezza [insulin human] inhalation powder administered using the Afrezza inhaler. In addition, subjects will take their personal basal insulin while enrolled in the study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Subjects ≥18 years of age at the time of signing the informed consent form
- Clinical diagnosis of T1DM or T2DM (per the Investigator) and on a stable basal-bolus insulin regimen
Key exclusion criteria (15 listed)
- History of asthma, chronic obstructive pulmonary disease, or any other clinically important pulmonary disease (e.g., cystic fibrosis, bronchopulmonary dysplasia), use of any medications to treat such conditions within the last year, or significant congenital or acquired cardiopulmonary disease
- History of serious complications of diabetes (e.g., active proliferative retinopathy or symptomatic autonomic neuropathy)
- On dialysis
- Respiratory tract infection within 14 days before screening (subject may return 14 days after resolution of symptoms for rescreening)
- Treatment with any investigational drug in the past 30 days or an investigational device in the past 2 weeks
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Afrezza Dose 1The first dose of Afrezza will be based on the dose of subcutaneous rapid-acting analogue (RAA) insulin that the subject would normally take for the standardized meal, converted according to the guidelines provided in the current Afrezza U.S. prescribing information. | Combination product | Afrezza |
| Afrezza Dose 2The second dose of Afrezza will be based on the dose of subcutaneous rapid-acting analogue that the subject would normally take for the standardized meal, converted by multiplying their RAA dose by 2 and rounding down to the nearest Afrezza cartridge size. | Combination product | Afrezza |
Primary outcome
Post-prandial Glucose Excursion
Time frame: 120 minutes post-dose
Mean glucose change from baseline (or postprandial glucose excursion [PPGE]) based on self-monitored blood glucose (SMBG) at 15, 30, 45, 60, 90 and 120 minutes after the dose of Afrezza with baseline defined as SMBG at the time of the dose of Afrezza (t=0)
6 secondary outcomes
Number of Subjects With at Least 1 Event of Level 1 Hypoglycemia
Time frame: 120 minutes
Percent of Level 1 Hypoglycemia
Time frame: 120 minutes
Number of Subjects With at Least 1 Event of Level 2 Hypoglycemia
Time frame: 120 minutes
Percent of Level 2 Hypoglycemia
Time frame: 120 minutes
Number of Subjects With At Least 1 Event of Severe Hypoglycemia
Time frame: 120 minutes
Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Between Two Points, Baseline and 120 Minutes Post-Afrezza Dose
Time frame: 120 minutes post-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kevin Kaiserman, MD study director
Mannkind Corporation
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Afrezza Dose 1 and Afrezza Dose 2 in people with Diabetes Mellitus, Type 1 and Diabetes Mellitus, Type 2, run by Mannkind Corporation at 2 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 2 inclusion and 15 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 18 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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?
Yes. Results are posted in the registry (first posted 18 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Post-prandial Glucose Excursion (time frame: 120 minutes post-dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Sep 2023.