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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
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):
The study is composed of up to 5 clinic visits (screening, 3 treatment visits, and an end-of-treatment visit) and 9 telephone visits.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Afrezza + Automatic Insulin Delivery | Experimental | 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. |
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| Afrezza + Insulin Degludec | Experimental | Subjects in this group will use Afrezza for their bolus (mealtime and correction) insulin and insulin degludec for basal insulin coverage. |
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| AID Control | Active Comparator | 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). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Afrezza (insulin human) Inhalation Powder | Biological | Pharmaceutical form: powder Route of administration: inhalation |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in HbA1c | Change in glycated hemoglobin (HbA1c) from baseline to end of study | 90 days |
| Measure | Description | Time Frame |
|---|---|---|
| Events of Level 1 Hypoglycemia (SMBG < 70mg/dL) | Events of hypoglycemia (SMBG <70 mg/dL for SMBG values more than 30 minutes apart) | 90 days |
| Events of Level 2 Hypoglycemia (SMBG < 54 mg/dL) | Events of hypoglycemia (SMBG <54 mg/dL for SMBG values more than 30 minutes apart) |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Percent Predicted Forced Expiratory Volume in 1 Second | Change in percent predicted forced expiratory volume in 1 second (FEV1) from baseline to end of study | baseline and 90 days |
| Total Number of Treatment-Emergent Adverse Events |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kevin Kaiserman, MD | Mannkind Corporation | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Diabetes Treatment Center, Loma Linda University | Loma Linda | California | 92354 | United States | ||
| Texas Diabetes and Endocrinology |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40531276 | Derived | Jacobson C, Kaiserman KB, Ulloa J, Pleitez J, Sylvan J, Rinker J, Codorniz K, Lee S, Vakhshoori M, Lobo Moreno P, Blevins T. Safety and Efficacy of Inhaled Technosphere(R) Insulin in the Postprandial Period With Modified Initial Dose Conversion. Diabetes Ther. 2025 Aug;16(8):1695-1705. doi: 10.1007/s13300-025-01760-5. Epub 2025 Jun 18. |
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Per protocol, participants who complete the informed consent process are enrolled in the study. In this study, 33 participants were enrolled in the study. The study has a run-in period of up to 28 days. After completion of the run-in period, and confirmation of all eligibility requirements, the participant may be assigned to a study arm/group. In this study, only 28 participants started the treatment phase and were assigned to a study arm/group (5 participants are considered PreRand drops).
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| ID | Title | Description |
|---|---|---|
| FG000 | Afrezza + Automatic Insulin Delivery (AID) | Subjects in this group will use Afrezza for their bolus (mealtime) insulin and a Continuous Subcutaneous Insulin Infusion (CSII) pump with an AID algorithm using Rapid Acting Insulin Analogs (RAA) for their basal and correction insulin coverage. Afrezza (insulin human) Inhalation Powder: Pharmaceutical form: powder Route of administration: inhalation CSII pump with AID: Acceptable AID systems in this study are Medtronic 670G/770G and Tandem Control IQ |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 20, 2022 | Oct 17, 2023 |
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| insulin degludec | Biological | Pharmaceutical form: solution for injection Route of administration: subcutaneous |
|
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| Continuous Subcutaneous Insulin Infusion (CSII) pump with Automatic Insulin Delivery (AID) | Device | Acceptable AID systems in this study are Medtronic 670G/770G and Tandem Control IQ |
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| 90 days |
| Events of Severe Hypoglycemia | Events of severe hypoglycemia requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions | 90 days |
| Change in Time in Range (Glucose of 70 - 180 mg/dL) | 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 | baseline and 90 days |
| Change in Time Below Range (Glucose <70 mg/dL) | 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 | baseline and 90 days |
| Change in Percentage of Time With Glucose <54 mg/dL | 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 | baseline and 90 days |
| Change in Time Above Range (Glucose >180 mg/dL) | 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 | baseline and 90 days |
| Change in Percentage of Time With Glucose >250 mg/dL | 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 | baseline and 90 days |
| Change in Coefficient of Variation (CV) | 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 | baseline and 90 days |
Total Number of Treatment-Emergent Adverse Events (TEAEs)
| 90 days |
| Total Number of Serious Adverse Events | Total Number of Serious Adverse Events (SAEs) | 90 days |
| Total Number of Adverse Events of Special Interest | Total Number of Adverse Events of Special Interest (AESIs) | 90 days |
| Total Number of Device Complaints | Total Number of Device Complaints | 90 days |
| Austin |
| Texas |
| 78731 |
| United States |
| FG001 | Afrezza + Insulin Degludec | Subjects in this group will use Afrezza for their bolus (mealtime and correction) insulin and insulin degludec for basal insulin coverage. Afrezza (insulin human) Inhalation Powder: Pharmaceutical form: powder Route of administration: inhalation insulin degludec: Pharmaceutical form: solution for injection Route of administration: subcutaneous |
| FG002 | 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). CSII pump with AID: Acceptable AID systems in this study are Medtronic 670G/770G and Tandem Control IQ |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Afrezza + Automatic Insulin Delivery (AID) | Subjects in this group will use Afrezza for their bolus (mealtime) insulin and a Continuous Subcutaneous Insulin Infusion (CSII) pump with an AID algorithm using Rapid Acting Insulin Analogs (RAA) for their basal and correction insulin coverage. Afrezza (insulin human) Inhalation Powder: Pharmaceutical form: powder Route of administration: inhalation CSII pump with AID: Acceptable AID systems in this study are Medtronic 670G/770G and Tandem Control IQ |
| BG001 | Afrezza + Insulin Degludec | Subjects in this group will use Afrezza for their bolus (mealtime and correction) insulin and insulin degludec for basal insulin coverage. Afrezza (insulin human) Inhalation Powder: Pharmaceutical form: powder Route of administration: inhalation insulin degludec: Pharmaceutical form: solution for injection Route of administration: subcutaneous |
| BG002 | 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). CSII pump with AID: Acceptable AID systems in this study are Medtronic 670G/770G and Tandem Control IQ |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in HbA1c | Change in glycated hemoglobin (HbA1c) from baseline to end of study | Posted | Mean | Standard Deviation | percent of glycated hemoglobin | 90 days |
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| Secondary | Events of Level 1 Hypoglycemia (SMBG < 70mg/dL) | Events of hypoglycemia (SMBG <70 mg/dL for SMBG values more than 30 minutes apart) | Posted | Mean | Standard Deviation | Count of events | 90 days |
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| Secondary | Events of Level 2 Hypoglycemia (SMBG < 54 mg/dL) | Events of hypoglycemia (SMBG <54 mg/dL for SMBG values more than 30 minutes apart) | Posted | Mean | Standard Deviation | Count of events | 90 days |
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| Secondary | Events of Severe Hypoglycemia | Events of severe hypoglycemia requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions | Posted | Number | Count of events | 90 days |
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| Secondary | Change in Time in Range (Glucose of 70 - 180 mg/dL) | 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 | Posted | Mean | Standard Deviation | percent of TIR | baseline and 90 days |
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| Secondary | Change in Time Below Range (Glucose <70 mg/dL) | 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 | Posted | Mean | Standard Deviation | percent of TBR | baseline and 90 days |
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| Secondary | Change in Percentage of Time With Glucose <54 mg/dL | 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 | Posted | Mean | Standard Deviation | percent of time with glucose <54mg/dL | baseline and 90 days |
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| Secondary | Change in Time Above Range (Glucose >180 mg/dL) | 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 | Posted | Mean | Standard Deviation | percent of TAR | baseline and 90 days |
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| Secondary | Change in Percentage of Time With Glucose >250 mg/dL | 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 | Posted | Mean | Standard Deviation | percent of time with glucose >250mg/dL | baseline and 90 days |
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| Secondary | Change in Coefficient of Variation (CV) | 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 | Posted | Mean | Standard Deviation | percent of coefficient of variation | baseline and 90 days |
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| Other Pre-specified | Change in Percent Predicted Forced Expiratory Volume in 1 Second | Change in percent predicted forced expiratory volume in 1 second (FEV1) from baseline to end of study | Posted | Mean | Standard Deviation | percent predicted FEV1 | baseline and 90 days |
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| Other Pre-specified | Total Number of Treatment-Emergent Adverse Events | Total Number of Treatment-Emergent Adverse Events (TEAEs) | Posted | Number | count of TEAEs | 90 days |
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| Other Pre-specified | Total Number of Serious Adverse Events | Total Number of Serious Adverse Events (SAEs) | Posted | Number | count of SAEs | 90 days |
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| Other Pre-specified | Total Number of Adverse Events of Special Interest | Total Number of Adverse Events of Special Interest (AESIs) | Posted | Number | count of AESIs | 90 days |
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| Other Pre-specified | Total Number of Device Complaints | Total Number of Device Complaints | Posted | Number | Count of Device Complaints | 90 days |
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Adverse Event data were collected for a period of up to 120 days.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Afrezza + Automatic Insulin Delivery (AID) | Subjects in this group will use Afrezza for their bolus (mealtime) insulin and a Continuous Subcutaneous Insulin Infusion (CSII) pump with an AID algorithm using Rapid Acting Insulin Analogs (RAA) for their basal and correction insulin coverage. Afrezza (insulin human) Inhalation Powder: Pharmaceutical form: powder Route of administration: inhalation CSII pump with AID: Acceptable AID systems in this study are Medtronic 670G/770G and Tandem Control IQ | 0 | 13 | 2 | 13 | 7 | 13 |
| EG001 | Afrezza + Insulin Degludec | Subjects in this group will use Afrezza for their bolus (mealtime and correction) insulin and insulin degludec for basal insulin coverage. Afrezza (insulin human) Inhalation Powder: Pharmaceutical form: powder Route of administration: inhalation insulin degludec: Pharmaceutical form: solution for injection Route of administration: subcutaneous | 0 | 10 | 1 | 10 | 8 | 10 |
| EG002 | 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). Continuous Subcutaneous Insulin Infusion (CSII) pump with Automatic Insulin Delivery (AID): Acceptable AID systems in this study are Medtronic 670G/770G and Tandem Control IQ | 0 | 5 | 0 | 5 | 1 | 5 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diabetic Ketoacidosis | Metabolism and nutrition disorders | Non-systematic Assessment |
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| Angina pectoris | Cardiac disorders | Non-systematic Assessment |
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| Localised infection | Infections and infestations | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| COVID-19 respiratory infection | Infections and infestations | Non-systematic Assessment |
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| Headache | Nervous system disorders | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | Non-systematic Assessment |
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| Urinary Tract Infection | Infections and infestations | Non-systematic Assessment |
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| Sinusitis | Infections and infestations | Non-systematic Assessment |
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| Cellulitis | Infections and infestations | Non-systematic Assessment |
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| Laryngitis | Infections and infestations | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
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| Anxiety | Psychiatric disorders | Non-systematic Assessment |
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| Bronchitis | Infections and infestations | Non-systematic Assessment | Secondary to COVID19 |
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| Decreased Appetitie | Metabolism and nutrition disorders | Non-systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Skin Irritation | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Obstructive sleep apnoea syndrome | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Anormal weight gain | Metabolism and nutrition disorders | Non-systematic Assessment |
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| Vertigo | Ear and labyrinth disorders | Non-systematic Assessment |
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| Actinic Keratosis | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Respiration Abnormal | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Pulmonary function test decreased | Investigations | Non-systematic Assessment |
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| Sneezing | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Upper Respiratory Tract Infection | Infections and infestations | Non-systematic Assessment |
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| Wheezing | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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Limitations of the study include its open-label and non-controlled study design and a small sample size (Total Started=28).
Neither the Institution nor the Principal Investigator will disclose any of the results arising out of or in connection with the Clinical Trial or information provided by the Sponsor to the Institution without the prior express written consent of the Sponsor.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jennifer Pleitez, Director of Clinical Operations | Mannkind Corporation | 818-661-5032 | endocrineresearch@mannkindcorp.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 31, 2022 | Oct 17, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| D003920 | Diabetes Mellitus |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D006946 | Hyperinsulinism |
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| ID | Term |
|---|---|
| D007328 | Insulin |
| C571886 | insulin degludec |
| ID | Term |
|---|---|
| D011384 | Proinsulin |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
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| Between 18 and 65 years |
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| >=65 years |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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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).
CSII pump with AID: Acceptable AID systems in this study are Medtronic 670G/770G and Tandem Control IQ
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