Type 1 Diabetes
Conditions
Brief summary
This US study will evaluate the safety and effectiveness of utilizing insulin Lyumjev® lispro-aabc in the MiniMed™ 780G System in Type 1 adult and pediatric subjects in a home setting to support product and system labeling.
Detailed description
This study is a multi-center, single arm study in insulin-requiring adult and pediatric subjects with type 1 diabetes on the MiniMed™ 780G system using Lyumjev® insulin lispro-aabc and Medtronic Extended infusion set and reservoir. The run-in period and study period will be approximately 120 days long. A total of up to 250 subjects with insulin-requiring type 1 diabetes age 7-80 will be enrolled at up to 25 investigational centers across the United States in order to have at least 200 subjects enter the study period. Up to 125 subjects will be enrolled in the pediatric age group (7-17 years of age) and up to 125 in the adult age group (18 years or older).
Interventions
DEVICEMiniMed 780G System
MiniMed™ 780G Insulin Pump, Guardian™ 4 Glucose Sensor, and Guardian 4 Transmitter; used with Insulin Lyumjev® insulin lispro-aabc
Sponsors
Eli Lilly and Company
Medtronic Diabetes
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
7 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age 7-80 years at time of screening. 2. Has a clinical diagnosis of type 1 diabetes: 1. 14-80 years of age: A clinical diagnosis of type 1 diabetes for 2 years or more as determined via medical record or source documentation by an individual qualified to make a medical diagnosis. 2. 7-13 years of age: A clinical diagnosis of type 1 diabetes for 1 year or more as determined via medical record or source documentation by an individual qualified to make a medical diagnosis. 3. Does not require a legally authorized representative to consent on their behalf due to mental or intellectual disability. 4. Subject or parent/caregiver is literate and able to read the language offered in the pump or pump materials. 5. Subject and/or legally authorized representative is willing to provide informed consent for participation. 6. Is willing to perform fingerstick blood glucose measurements as needed. 7. Is willing to wear the system continuously throughout the study. 8. Must have a minimum daily insulin requirement (Total Daily Dose) of greater than or equal to 8 units and a maximum total daily dose of 250 units or less. 9. Has a Glycosylated hemoglobin (HbA1c) less than 10% (as processed by Central Lab) at time of screening visit. Note: All HbA1c blood specimens will be sent to and tested by a National Glycohemoglobin Standardization Program (NGSP) certified Central Laboratory. HbA1c testing must follow NGSP standards. 10. Has thyroid-stimulating hormone (TSH) in the normal range OR if the TSH is out of normal reference range, the Free T3 is below or within the lab's reference range and Free T4 is within the normal reference range. 11. Uses pump therapy for greater than 6 months (with or without CGM experience) prior to screening 12. Is willing to upload data from the study pump, must have Internet access, and a computer system, or compatible smartphone that meets the requirements for uploading the study pump. 13. Is willing to take one of the following insulins and can financially support the use of insulin preparations as required during the run-in period: 1. Humalog (insulin lispro injection) 2. NovoLog (insulin aspart injection) 3. Admelog(insulin lispro injection) 14. Is willing to take Lyumjev insulin during the study period (supplied via Sponsor).
Exclusion criteria
1. Has hypersensitivity to insulin lispro or one of the excipients in Lyumjev® 2. Has a history of 2 or more episodes of severe hypoglycemia, which resulted in any the following during the 6 months prior to screening: 1. Medical assistance (i.e., Paramedics, Emergency Room \[ER\] or Hospitalization) 2. Coma 3. Seizures 3. Has been hospitalized or has visited the ER in the 6 months prior to screening resulting in a primary diagnosis of uncontrolled diabetes. 4. Has had DKA in the last 6 months prior to screening visit. 5. Will not tolerate tape adhesive in the area of sensor placement as assessed by a qualified individual. 6. Has any unresolved adverse skin condition in the area of sensor placement (e.g., psoriasis, dermatitis herpetiformis, rash, Staphylococcus infection). 7. Is female of child-bearing potential and result of pregnancy test is positive at screening. 8. Is sexually active female of child-bearing potential and is not using a form of contraception deemed reliable by the investigator. 9. Is female and plans to become pregnant during the course of the study 10. Is being treated for hyperthyroidism at time of screening. 11. Has diagnosis of adrenal insufficiency. 12. Has taken any oral, injectable, or intravenous (IV) glucocorticoids within 8 weeks from time of screening visit, or plans to take any oral, injectable, or IV glucocorticoid during the course of the study. 13. Is using hydroxyurea at time of screening or plans to use it during the study. 14. Is actively participating in an investigational study (drug or device) wherein he/she has received treatment from an investigational study drug or investigational study device in the last 2 weeks. 15. Is currently abusing illicit drugs. 16. Is currently abusing marijuana. 17. Is currently abusing prescription drugs. 18. Is currently abusing alcohol. 19. Using pramlintide (Symlin), DPP-4 inhibitor, liraglutide (Victoza or other GLP-1 agonists), metformin, canagliflozin (Invokana or other SGLT2 inhibitors) at time of screening. 20. Has a history of visual impairment which would not allow subject to participate in the study and perform all study procedures safely, as determined by the investigator. 21. Has elective surgery planned that requires general anesthesia during the course of the study. 22. Has sickle cell disease, hemoglobinopathy; or has received red blood cell transfusion or erythropoietin within 3 months prior to time of screening. 23. Plans to receive red blood cell transfusion or erythropoietin over the course of study participation. 24. Is diagnosed with current eating disorder such as anorexia or bulimia. 25. Has been diagnosed with chronic kidney disease that results in chronic anemia. 26. Has a hematocrit that is below the normal reference range of lab used. 27. Is on dialysis. 28. Has serum creatinine of \>2 mg/dL. 29. Has celiac disease that is not adequately treated as determined by the investigator. 30. Has had any of the following cardiovascular events within 1 year of screening: myocardial infarction, unstable angina, coronary artery bypass surgery, coronary artery stenting, transient ischemic attack, cerebrovascular accident, angina, congestive heart failure, or ventricular rhythm disturbances. 31. Has had history of cardiovascular event 1 year or more from the time of screening without 1. a normal EKG and stress test within 6 months prior to screening or during screening or 2. clearance from a qualified physician prior to receiving the study devices if there is an abnormal EKG or stress test. 32. Has 3 or more cardiovascular risk factors listed below without a normal EKG within 6 months prior to screening or during screening or clearance from a qualified physician if there is an abnormal EKG: * Age \>35 years * Type 1 diabetes of \>15 years' duration * Presence of any additional risk factor for coronary artery disease * Presence of microvascular disease (proliferative retinopathy or nephropathy, including microalbuminuria) * Presence of peripheral vascular disease * Presence of autonomic neuropathy 33. Is a member of the research staff involved with the study. 34. Has used a MiniMed 780G pump prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Safety Endpoint - Change in HbA1c | 3 months | The overall mean change in HbA1c from baseline to end of 3-month study period. Non-inferiority test. |
| Primary Effectiveness Endpoint - Percent of Time in Range (TIR 70-180 mg/dL) | Last 6-7 weeks of 3 month study period | The mean % of time in range (TIR 70-180 mg/dL). Non-inferiority test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Effectiveness Endpoint 1 - Percent of Time in Hypoglycemia (< 54 mg/dL) | Last 6-7 weeks of 3 month study period | The mean % of time in hypoglycemia (\< 54 mg/dL). Non-inferiority test. |
| Secondary Effectiveness Endpoint 2 - Percent of Time in Range (TIR 70-180 mg/dL) | Last 6-7 weeks of 3 month study period | The mean % of time in range (TIR 70-180 mg/dL). Superiority test. |
Countries
United States
Participant flow
Pre-assignment details
244 subjects (120 with age 7-17 and 124 with age 18-80) enrolled at the beginning, with 23 (12 with age 7-17 and 11 with age 18-80) screen failure, 10 subjects (7 with age 7-17 and 3 with age 18-80) early withdrawn prior the study period, 211 subjects (101 with age 7-17 and 110 with age 18-80) started the study and became the Intention to Treat Population.
Participants by arm
| Arm | Count |
|---|---|
| Subjects 7-17 Years of Age Subjects with insulin-requiring type 1 diabetes age 7-17 using the MiniMed 780G system with Insulin Lyumjev® for a period of three months.
MiniMed 780G System: MiniMed™ 780G Insulin Pump, Guardian™ 4 Glucose Sensor, and Guardian 4 Transmitter; used with Insulin Lyumjev® insulin lispro-aabc | 101 |
| Subjects 18-80 Years of Age Subjects with insulin-requiring type 1 diabetes age 18-80 using the MiniMed 780G system with Insulin Lyumjev® for a period of three months.
MiniMed 780G System: MiniMed™ 780G Insulin Pump, Guardian™ 4 Glucose Sensor, and Guardian 4 Transmitter; used with Insulin Lyumjev® insulin lispro-aabc | 110 |
| Total | 211 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Sponsor Request | 0 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | Subjects 18-80 Years of Age | Subjects 7-17 Years of Age | Total |
|---|---|---|---|
| Age, Continuous | 45.0 years STANDARD_DEVIATION 14.2 | 13.0 years STANDARD_DEVIATION 2.6 | 29.7 years STANDARD_DEVIATION 19.1 |
| BMI | 28.8 kg/m^2 STANDARD_DEVIATION 5.3 | 22.0 kg/m^2 STANDARD_DEVIATION 4.6 | 25.6 kg/m^2 STANDARD_DEVIATION 6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 19 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 103 Participants | 81 Participants | 184 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 8 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) White | 103 Participants | 85 Participants | 188 Participants |
| Sex: Female, Male Female | 49 Participants | 51 Participants | 100 Participants |
| Sex: Female, Male Male | 61 Participants | 50 Participants | 111 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 101 | 0 / 110 |
| other Total, other adverse events | 50 / 101 | 47 / 110 |
| serious Total, serious adverse events | 0 / 101 | 0 / 110 |
Outcome results
Primary
Primary Effectiveness Endpoint - Percent of Time in Range (TIR 70-180 mg/dL)
The mean % of time in range (TIR 70-180 mg/dL). Non-inferiority test.
Time frame: Last 6-7 weeks of 3 month study period
Population: Intention to Treat Population with available data. Three subjects aged 7-17 and eight subject aged 18-80 did not have enough SG points at the last 6 weeks of the study period, so 98 subjects aged 7-17 and 102 subjects aged 18-80 were analyzed at last 6 weeks of study period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects 7-17 Years of Age | Primary Effectiveness Endpoint - Percent of Time in Range (TIR 70-180 mg/dL) | 68.6 percentage of Time in Range (TIR 70-180 | Standard Deviation 10.3 |
| Subjects 18-80 Years of Age | Primary Effectiveness Endpoint - Percent of Time in Range (TIR 70-180 mg/dL) | 77.6 percentage of Time in Range (TIR 70-180 | Standard Deviation 9.6 |
p-value: <0.00195% CI: [66.6, 70.7]t-test, 1 sided
p-value: <0.00195% CI: [75.7, 79.4]t-test, 1 sided
Primary
Primary Safety Endpoint - Change in HbA1c
The overall mean change in HbA1c from baseline to end of 3-month study period. Non-inferiority test.
Time frame: 3 months
Population: Intention to Treat Population with available data. Two subjects aged 7-17 and two subject aged 18-80 did not collect A1C at the end of the study period, so 99 subjects aged 7-17 and 108 subjects aged 18-80 were analyzed at end of study period and the change from baseline to end of study period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects 7-17 Years of Age | Primary Safety Endpoint - Change in HbA1c | -0.1 percentage of HbA1c | Standard Deviation 0.7 |
| Subjects 18-80 Years of Age | Primary Safety Endpoint - Change in HbA1c | -0.4 percentage of HbA1c | Standard Deviation 0.6 |
p-value: 0.13395% CI: [-0.2, 0.1]t-test, 1 sided
p-value: <0.00195% CI: [-0.6, -0.3]Wilcoxon (Mann-Whitney)
Secondary
Secondary Effectiveness Endpoint 1 - Percent of Time in Hypoglycemia (< 54 mg/dL)
The mean % of time in hypoglycemia (\< 54 mg/dL). Non-inferiority test.
Time frame: Last 6-7 weeks of 3 month study period
Population: Intention to Treat Population with available data. Three subjects aged 7-17 and eight subject aged 18-80 did not have enough SG points at the last 6 weeks of the study period, so 98 subjects aged 7-17 and 102 subjects aged 18-80 were analyzed at last 6 weeks of study period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects 7-17 Years of Age | Secondary Effectiveness Endpoint 1 - Percent of Time in Hypoglycemia (< 54 mg/dL) | 0.4 percentage of Time in Hypoglycemia (< 54 | Standard Deviation 0.5 |
| Subjects 18-80 Years of Age | Secondary Effectiveness Endpoint 1 - Percent of Time in Hypoglycemia (< 54 mg/dL) | 0.2 percentage of Time in Hypoglycemia (< 54 | Standard Deviation 0.3 |
p-value: <0.00195% CI: [0.3, 0.5]Wilcoxon (Mann-Whitney)
p-value: <0.00195% CI: [0.2, 0.3]Wilcoxon (Mann-Whitney)
Secondary
Secondary Effectiveness Endpoint 2 - Percent of Time in Range (TIR 70-180 mg/dL)
The mean % of time in range (TIR 70-180 mg/dL). Superiority test.
Time frame: Last 6-7 weeks of 3 month study period
Population: Intention to Treat Population with available data. Three subjects aged 7-17 and eight subject aged 18-80 did not have enough SG points at the last 6 weeks of the study period, so 98 subjects aged 7-17 and 102 subjects aged 18-80 were analyzed at last 6 weeks of study period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects 7-17 Years of Age | Secondary Effectiveness Endpoint 2 - Percent of Time in Range (TIR 70-180 mg/dL) | 68.6 percentage of Time in Range (TIR 70-180 | Standard Deviation 10.3 |
| Subjects 18-80 Years of Age | Secondary Effectiveness Endpoint 2 - Percent of Time in Range (TIR 70-180 mg/dL) | 77.6 percentage of Time in Range (TIR 70-180 | Standard Deviation 9.6 |
p-value: <0.00195% CI: [66.6, 70.7]t-test, 1 sided
p-value: <0.00195% CI: [75.7, 79.4]t-test, 1 sided