Diabetes Mellitus, Type 1
Conditions
Keywords
T1D, Type 1 diabetes, Mini-dose glucagon, adults, non-severe hypoglycemia
Brief summary
The purpose of this study is to determine if a small dose of glucagon (mini-dose glucagon) is effective for the treatment of non-severe hypoglycemia in adults with type 1 diabetes (T1D).
Detailed description
There are three phases included in this study: (1) Pre-crossover Trial Run-in Phase, (2) Randomized Clinical Trial (RCT) Crossover Trial Phase, and (3) Post-Crossover Trial Extension Phase. 1. Run-in Phase: Prior to commencing the crossover trial, study enrollment will begin with a 2 week run-in phase to assess hypoglycemia eligibility and compliance. 2. Crossover Trial Phase: The Crossover Trial Phase will consist of two (3-week) periods. The Crossover Trial Phase will include up to 24 participants who complete these study periods. Participants who do not complete both periods or who do not have at least one event during both periods may be replaced. During the Crossover Trial Phase participants will be randomized into two groups: (1) Group A will use mini-dose glucagon in period 1 and oral glucose tablets in period 2 and (2) Group B will use oral glucose tablets in period 1 and mini-dose glucagon in period 2. Each group with follow the applicable treatment arm according to their randomized group. 3. Extension Phase: The Post-Crossover Trial phase will commence upon completion of the second 3-week period of the Crossover Trial Phase. Participants will have a 3 week phase during which time they will decide whether to use mini-dose glucagon or glucose tablets to treat each non-severe hypoglycemic event or to prevent hypoglycemia.
Interventions
1st BG check, 1st treatment 1. BG is 50-69 mg/dl, treatment is 150 µg of glucagon 2. BG is 40-49 mg/dl, treatment is 300 µg of glucagon 15 min later, 2nd BG check, 2nd treatment 1. BG is 60-69 mg/dl, no treatment 2. BG is 50-59 mg/dl, treatment is 150 µg of glucagon 3. BG is \<50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment 1. BG is \>=70, no treatment 2. BG is \<70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon (150 µg of glucagon per syringe)
OTHERGlucose Tablets
1st BG check, 1st treatment 1. BG is 50-69 mg/dl, treatment is 15 grams of carbohydrates 2. BG is 40-49 mg/dl, treatment is 30 grams of carbohydrates 15 min later, 2nd BG check, 2nd treatment 1. BG is 60-69 mg/dl, no treatment 2. BG is 50-59 mg/dl, treatment is 15 grams of carbohydrates 3. BG is \<50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment 1. BG is \>=70, no treatment 2. BG is \<70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon (5 grams of fast-acting carbohydrates (D-Glucose) per tablet)
Sponsors
Xeris Pharmaceuticals
Jaeb Center for Health Research
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
1. Clinical diagnosis of presumed autoimmune T1D and receiving daily insulin 2. Age: 18.0 to \< 65.0 years 3. Duration of T1D: ≥2.0 years 4. Body mass index 20.0 to \<35.0 kg/m2 and weight 110 to \<250 lbs 5. HbA1c \<8.5% (point of care or local lab, within past month) 6. Using continuous subcutaneous insulin infusion (CSII) therapy (i.e., insulin pump) for at least 3 months, with no plans to discontinue use during the study (and no use of active low glucose suspend feature within the last 4 weeks) 7. Using continuous glucose monitor ≥6 days/week in the last 4 weeks, with no plans to discontinue continuous glucose monitor use during the study 8. Continuous glucose monitor glucose level \<70 mg/dl during daytime hours (e.g., 8am - 10pm) on at least 7 of the past 28 days (a modification can be made for participants with non-traditional waking hours) evaluated from downloaded CGM data 9. Females must meet one of the following criteria: * Of childbearing potential and not currently pregnant (negative pregnancy test) or lactating, and agrees to use an accepted contraceptive regimen as described in the study procedure manual throughout the entire duration of the study (from screening visit until study completion); or * Of non-childbearing potential, defined as a female who has had a hysterectomy or tubal ligation, is clinically considered infertile or is in a menopausal state (at least 1 year without menses) 10. In good general health with no conditions that could influence the outcome of the trial, and in the judgment of the investigator is a good candidate for the study based on review of available medical history, physical examination and clinical laboratory evaluations 11. Willing to adhere to the protocol requirements for the duration of the study 12. Participant has a smart phone available and is able to use it daily 13. Must be enrolled in the T1D Exchange clinic registry or willing to join the clinic registry
Exclusion criteria
1. More than 1 severe hypoglycemic episode in the past 12 months (as defined by an episode that required third party assistance for treatment) 2. More than 1 episode of diabetic ketoacidosis in the past 12 months (as defined by an episode diagnosed as diabetic ketoacidosis that required treatment in an emergency department or hospitalization) 3. Presence of cardiovascular, gastrointestinal, liver or kidney disease, or any medical condition which, in the judgment of the investigator, could potentiate or predispose to undesired effects or could interfere with the absorption, distribution, metabolism, or excretion of glucagon or ability to respond appropriately to mild to moderate hypoglycemia. 4. Known presence of hereditary problems of glycogen storage disease, galactose and/or lactose intolerance 5. Males with alcohol use in excess of 3 or more drinks per day, on average and females with alcohol use in excess of 2 or more drinks per day, on average 6. Use of non-insulin anti-diabetic medications 7. Use of daily systemic beta-blocker 8. Use of beta-adrenergic agonists, theophylline (or other methylxanthines) 9. Use of 1st generation anticholinergic drugs (such as Brompheniramine, Chlorpheniramine, Dimenhydrinate, Diphenhydramine, and Doxylamine) 10. Use of systemic corticosteroids 11. History of hypersensitivity to glucagon or any related product or excipient or severe hypersensitivity reactions (such as angioedema) to any drugs 12. History of epilepsy or seizure disorder 13. Uncontrolled hypertension, \>160 mmHg systolic or \>100 mmHg diastolic 14. Currently a high endurance exerciser or plans to perform high endurance exercise during study (from screening visit until study completion) * High endurance exerciser defined as a person who regularly competes in running, cycling, rowing, swimming or any other endurance-based activity for the purpose of competition (\>2100 metabolic equivalent of task (MET) minutes per week \[i.e. 7 METs x 60 minutes x 5 days a week, where 7 METs is equivalent to jogging\]) 15. Currently following a very low calorie or other weight-loss diet 16. Participation in other studies involving administration of an investigational drug or device within 30 days or 5 half-lives, whichever is longer, before screening for the current study or planning to participate in another such study during participation in the current study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Hypoglycemic Events ≥50 mg/dl 15 Minutes AND ≥ 70 mg/dl 30 Minutes After Initial Treatment | 30 minutes |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Continuous Glucose Monitor (CGM) Minimum Glucose, Event Level | 60 Minutes | Minimum glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event |
| CGM Maximum Glucose, Event Level | 60 Minutes | Maximum glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event |
| CGM Mean Glucose, Event Level | 60 Minutes | Median (IQR) reported for mean glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event |
| CGM Time in Range, Event Level | 60 Minutes | Percentage of time 70-180 mg/dL from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event |
| CGM Time Below 70 mg/dL, Event Level | 60 Minutes | Percentage of time \<70 mg/dL from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event |
| CGM Coefficient of Variation | 3 weeks | Coefficient of Variation from CGM data computed over entire 3 weeks of treatment period |
| CGM Time Below 70 mg/dL | 120 Minutes | Percentage of time \<70 mg/dL from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first 2 hours after start of hypoglycemic event |
| CGM Mean Glucose | 3 weeks | Median (IQR) reported for mean glucose from CGM data computed over entire 3 weeks of treatment period |
| CGM Time in Range | 3 weeks | Percentage of time 70-180 mg/dL from CGM data computed over entire 3 weeks of treatment period |
| CGM Time Below 70 | 3 weeks | Percentage of time \<70 mg/dL from CGM data computed over entire 3 weeks of treatment period |
| CGM Minimum Glucose, Event Level | 120 Minutes | Minimum glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first 2 hours after start of hypoglycemic event |
Countries
United States
Participant flow
Pre-assignment details
26 consented for Run-in; 1 ineligible after consent; 2 ineligible after Run-in phase; 3 withdrew
Participants by arm
| Arm | Count |
|---|---|
| G-Pen Mini™ (Glucagon Injection), Then Glucose Tabs For G-Pen Mini Period:
Participants are to check blood glucose (BG) with study meter if continuous glucose monitor (CGM) reads \<70 mg/dl or they experience symptoms. Participants instructed to treat using mini-dose glucagon for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event).
G-Pen Mini™ (glucagon injection): 1st BG check, 1st treatment
1. BG is 50-69 mg/dl, treatment is 150 µg of glucagon
2. BG is 40-49 mg/dl, treatment is 300 µg of glucagon
15 min later, 2nd BG check, 2nd treatment
1. BG is 60-69 mg/dl, no treatment
2. BG is 50-59 mg/dl, treatment is 150 µg of glucagon
3. BG is \<50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon
30 minutes later, 3rd BG check, 3rd treatment
1. BG is \>=70, no treatment
2. BG is \<70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon | 6 |
| Glucose Tabs, Then G-Pen Mini For Glucose Tabs Period:
Participants are to check blood glucose (BG) with study meter if continuous glucose meter reads \<70 mg/dl or they experience symptoms. Participants instructed to treat using oral glucose tablets for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event).
Glucose Tabs: 1st BG check, 1st treatment:
1. BG is 50-69 mg/dl, treatment is 15 grams of carbohydrates
2. BG is 40-49 mg/dl, treatment is 30 grams of carbohydrates
15 min later, 2nd BG check, 2nd treatment
1. BG is 60-69 mg/dl, no treatment
2. BG is 50-59 mg/dl, treatment is 15 grams of carbohydrates
3. BG is \<50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon
30 minutes later, 3rd BG check, 3rd treatment
1. BG is \>=70 mg/dl, no treatment
2. BG is \<70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon | 10 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Crossover Trial Phase | Pregnancy | 0 | 1 |
Baseline characteristics
| Characteristic | G-Pen Mini™ (Glucagon Injection), Then Glucose Tabs | Total | Glucose Tabs, Then G-Pen Mini |
|---|---|---|---|
| Age, Continuous | 41.5 years STANDARD_DEVIATION 9.1 | 38.6 years STANDARD_DEVIATION 11 | 36.9 years STANDARD_DEVIATION 12.2 |
| Duration of Type 1 Diabetes | 24.8 years STANDARD_DEVIATION 14.2 | 23.4 years STANDARD_DEVIATION 14.8 | 22.5 years STANDARD_DEVIATION 15.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 16 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Hemoglobin A1c | 6.9 % STANDARD_DEVIATION 0.6 | 7.2 % STANDARD_DEVIATION 0.8 | 7.4 % STANDARD_DEVIATION 0.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 16 Participants | 10 Participants |
| Sex: Female, Male Female | 3 Participants | 12 Participants | 9 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 2 / 20 | 1 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Number of Hypoglycemic Events ≥50 mg/dl 15 Minutes AND ≥ 70 mg/dl 30 Minutes After Initial Treatment
Time frame: 30 minutes
Population: Limited to events with starting BG of 50-69 mg/dL
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| G-Pen Mini™ (Glucagon Injection) | Number of Hypoglycemic Events ≥50 mg/dl 15 Minutes AND ≥ 70 mg/dl 30 Minutes After Initial Treatment | 58 Hypoglycemic Events |
| Glucose Tabs | Number of Hypoglycemic Events ≥50 mg/dl 15 Minutes AND ≥ 70 mg/dl 30 Minutes After Initial Treatment | 53 Hypoglycemic Events |
Comparison: For the crossover trial primary analysis, analyzed events were study treatment events meeting the following criteria: a) a survey was completed in the smart phone application, b) the initial BG measurement was 40 to 69 mg/dL, c) BG measurements were performed at both the 15-minute (in a window of 13 to 20 minutes) and 30-minute (28 to 40 minutes) time points, and d) appropriate treatment including dose was taken both at the initial and 15-minute time points.p-value: 0.99Mixed Models Analysis
Secondary
CGM Coefficient of Variation
Coefficient of Variation from CGM data computed over entire 3 weeks of treatment period
Time frame: 3 weeks
Population: Limited to participants who had at least 72 hours of CGM data during each period
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| G-Pen Mini™ (Glucagon Injection) | CGM Coefficient of Variation | 35 percentage coefficient of variation |
| Glucose Tabs | CGM Coefficient of Variation | 36 percentage coefficient of variation |
p-value: 0.7Mixed Models Analysis
Secondary
CGM Maximum Glucose, Event Level
Maximum glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event
Time frame: 60 Minutes
Population: A participant had to have sufficient calibrations using study BGM to compare BGM and CGM data to ensure matching dates and times. Event level requirements: 1) initial treatment and dose had to be correct, 2) ≥6 CGM readings within 1 hour after initial treatment, and 3) first CGM glucose after the start of the hypoglycemic event had to be \<80 mg/dL
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| G-Pen Mini™ (Glucagon Injection) | CGM Maximum Glucose, Event Level | 102 mg/dL |
| Glucose Tabs | CGM Maximum Glucose, Event Level | 116 mg/dL |
p-value: 0.01Mixed Models Analysis
Secondary
CGM Maximum Glucose, Event Level
Maximum glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first 2 hours after start of hypoglycemic event
Time frame: 120 Minutes
Population: A participant had to have sufficient calibrations using study BGM to compare BGM and CGM data to ensure matching dates and times. Event level requirements: 1) initial treatment and dose had to be correct, 2) ≥6 CGM readings within 1 hour after initial treatment, and 3) first CGM glucose after the start of the hypoglycemic event had to be \<80 mg/dL
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| G-Pen Mini™ (Glucagon Injection) | CGM Maximum Glucose, Event Level | 122 mg/dL |
| Glucose Tabs | CGM Maximum Glucose, Event Level | 139 mg/dL |
p-value: 0.21Mixed Models Analysis
Secondary
CGM Mean Glucose
Median (IQR) reported for mean glucose from CGM data computed over entire 3 weeks of treatment period
Time frame: 3 weeks
Population: Limited to participants who had at least 72 hours of CGM data during each period
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| G-Pen Mini™ (Glucagon Injection) | CGM Mean Glucose | 143 mg/dL |
| Glucose Tabs | CGM Mean Glucose | 149 mg/dL |
p-value: 0.41Mixed Models Analysis
Secondary
CGM Mean Glucose, Event Level
Median (IQR) reported for mean glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event
Time frame: 60 Minutes
Population: A participant had to have sufficient calibrations using study BGM to compare BGM and CGM data to ensure matching dates and times. Event level requirements: 1) initial treatment and dose had to be correct, 2) ≥6 CGM readings within 1 hour after initial treatment, and 3) first CGM glucose after the start of the hypoglycemic event had to be \<80 mg/dL
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| G-Pen Mini™ (Glucagon Injection) | CGM Mean Glucose, Event Level | 79 mg/dL |
| Glucose Tabs | CGM Mean Glucose, Event Level | 87 mg/dL |
p-value: 0.02Mixed Models Analysis
Secondary
CGM Mean Glucose, Event Level
Median (IQR) reported for mean glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first 2 hours after start of hypoglycemic event
Time frame: 120 Minutes
Population: A participant had to have sufficient calibrations using study BGM to compare BGM and CGM data to ensure matching dates and times. Event level requirements: 1) initial treatment and dose had to be correct, 2) ≥6 CGM readings within 1 hour after initial treatment, and 3) first CGM glucose after the start of the hypoglycemic event had to be \<80 mg/dL
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| G-Pen Mini™ (Glucagon Injection) | CGM Mean Glucose, Event Level | 95 mg/dL |
| Glucose Tabs | CGM Mean Glucose, Event Level | 108 mg/dL |
p-value: 0.09Mixed Models Analysis
Secondary
CGM Minimum Glucose, Event Level
Minimum glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first 2 hours after start of hypoglycemic event
Time frame: 120 Minutes
Population: A participant had to have sufficient calibrations using study BGM to compare BGM and CGM data to ensure matching dates and times. Event level requirements: 1) initial treatment and dose had to be correct, 2) ≥6 CGM readings within 1 hour after initial treatment, and 3) first CGM glucose after the start of the hypoglycemic event had to be \<80 mg/dL
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| G-Pen Mini™ (Glucagon Injection) | CGM Minimum Glucose, Event Level | 57 mg/dL |
| Glucose Tabs | CGM Minimum Glucose, Event Level | 56 mg/dL |
p-value: 0.78Mixed Models Analysis
Secondary
CGM Time Below 70
Percentage of time \<70 mg/dL from CGM data computed over entire 3 weeks of treatment period
Time frame: 3 weeks
Population: Limited to participants who had at least 72 hours of CGM data during each period
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| G-Pen Mini™ (Glucagon Injection) | CGM Time Below 70 | 5 percentage of time |
| Glucose Tabs | CGM Time Below 70 | 4 percentage of time |
p-value: 0.13Mixed Models Analysis
Secondary
CGM Time Below 70 mg/dL
Percentage of time \<70 mg/dL from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first 2 hours after start of hypoglycemic event
Time frame: 120 Minutes
Population: A participant had to have sufficient calibrations using study BGM to compare BGM and CGM data to ensure matching dates and times. Event level requirements: 1) initial treatment and dose had to be correct, 2) ≥6 CGM readings within 1 hour after initial treatment, and 3) first CGM glucose after the start of the hypoglycemic event had to be \<80 mg/dL
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| G-Pen Mini™ (Glucagon Injection) | CGM Time Below 70 mg/dL | 20 percentage of time |
| Glucose Tabs | CGM Time Below 70 mg/dL | 19 percentage of time |
p-value: 0.63Mixed Models Analysis
Secondary
CGM Time Below 70 mg/dL, Event Level
Percentage of time \<70 mg/dL from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event
Time frame: 60 Minutes
Population: A participant had to have sufficient calibrations using study BGM to compare BGM and CGM data to ensure matching dates and times. Event level requirements: 1) initial treatment and dose had to be correct, 2) ≥6 CGM readings within 1 hour after initial treatment, and 3) first CGM glucose after the start of the hypoglycemic event had to be \<80 mg/dL
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| G-Pen Mini™ (Glucagon Injection) | CGM Time Below 70 mg/dL, Event Level | 35 percentage of time |
| Glucose Tabs | CGM Time Below 70 mg/dL, Event Level | 33 percentage of time |
p-value: 0.95Mixed Models Analysis
Secondary
CGM Time in Range
Percentage of time 70-180 mg/dL from CGM data computed over entire 3 weeks of treatment period
Time frame: 3 weeks
Population: Limited to participants who had at least 72 hours of CGM data during each period
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| G-Pen Mini™ (Glucagon Injection) | CGM Time in Range | 71 percentage of time |
| Glucose Tabs | CGM Time in Range | 71 percentage of time |
p-value: 0.8Mixed Models Analysis
Secondary
CGM Time in Range, Event Level
Percentage of time 70-180 mg/dL from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first 2 hours after start of hypoglycemic event
Time frame: 120 Minutes
Population: A participant had to have sufficient calibrations using study BGM to compare BGM and CGM data to ensure matching dates and times. Event level requirements: 1) initial treatment and dose had to be correct, 2) ≥6 CGM readings within 1 hour after initial treatment, and 3) first CGM glucose after the start of the hypoglycemic event had to be \<80 mg/dL
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| G-Pen Mini™ (Glucagon Injection) | CGM Time in Range, Event Level | 79 percentage of time |
| Glucose Tabs | CGM Time in Range, Event Level | 79 percentage of time |
p-value: 0.49Mixed Models Analysis
Secondary
CGM Time in Range, Event Level
Percentage of time 70-180 mg/dL from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event
Time frame: 60 Minutes
Population: A participant had to have sufficient calibrations using study BGM to compare BGM and CGM data to ensure matching dates and times. Event level requirements: 1) initial treatment and dose had to be correct, 2) ≥6 CGM readings within 1 hour after initial treatment, and 3) first CGM glucose after the start of the hypoglycemic event had to be \<80 mg/dL
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| G-Pen Mini™ (Glucagon Injection) | CGM Time in Range, Event Level | 62 percentage of time |
| Glucose Tabs | CGM Time in Range, Event Level | 67 percentage of time |
p-value: 0.86Mixed Models Analysis
Secondary
Continuous Glucose Monitor (CGM) Minimum Glucose, Event Level
Minimum glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event
Time frame: 60 Minutes
Population: A participant had to have sufficient calibrations using study BGM to compare BGM and CGM data to ensure matching dates and times. Event level requirements: 1) initial treatment and dose had to be correct, 2) ≥6 CGM readings within 1 hour after initial treatment, and 3) first CGM glucose after the start of the hypoglycemic event had to be \<80 mg/dL
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| G-Pen Mini™ (Glucagon Injection) | Continuous Glucose Monitor (CGM) Minimum Glucose, Event Level | 59 mg/dL |
| Glucose Tabs | Continuous Glucose Monitor (CGM) Minimum Glucose, Event Level | 56 mg/dL |
p-value: 0.34Mixed Models Analysis
Post Hoc
Clinical Grading - Initial and 15-min Treatment Correct
2 graders, blinded to treatment arm, independently graded each hypoglycemic event as a clinical failure or success based on all available BG concentrations within 1 hour of initial treatment. All BG values, along with corresponding time elapsed since treatment, were reviewed to determine whether the response would be considered a treatment success, in a clinical setting. There were no specific cut points; rather than basing the success criteria on whether the BG was above specific cutpoints by specific times, the grader decided whether the event would be considered a success in a clinical setting (i.e. if the BG increased after treatment and reached and maintained a satisfactory level after the treatment). The graders to achieve a consensus grading adjudicated discordant gradings (6% of events). The number of events graded as a treatment success were reported out of the total number of hypoglycemic events, for each treatment arm.
Time frame: 60 minutes
Population: Analysis was limited to hypoglycemic events where Initial and 15-min Treatment were correct.~4 hypoglycemic events were deemed Indeterminate by the graders during the glucagon period.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| G-Pen Mini™ (Glucagon Injection) | Clinical Grading - Initial and 15-min Treatment Correct | 66 Hypoglycemic Events |
| Glucose Tabs | Clinical Grading - Initial and 15-min Treatment Correct | 63 Hypoglycemic Events |
p-value: 0.66Mixed Models Analysis
Post Hoc
Clinical Grading - Initial Treatment Correct
2 graders, blinded to treatment arm, independently graded each hypoglycemic event as a clinical failure or success based on all available BG concentrations within 1 hour of initial treatment. All BG values, along with corresponding time elapsed since treatment, were reviewed to determine whether the response would be considered a treatment success, in a clinical setting. There were no specific cut points; rather than basing the success criteria on whether the BG was above specific cutpoints by specific times, the grader decided whether the event would be considered a success in a clinical setting (i.e. if the BG increased after treatment and reached and maintained a satisfactory level after the treatment). The graders to achieve a consensus grading adjudicated discordant gradings (6% of events). The number of events graded as a treatment success were reported out of the total number of hypoglycemic events, for each treatment arm.
Time frame: 60 minutes
Population: This analysis included all hypoglycemic events in which the initial treatment and dose were correct, irrespective of the timing of the BG measurements.~8 hypoglycemic events were deemed Indeterminate by the graders during the glucagon period and 4 during the glucose tabs period.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| G-Pen Mini™ (Glucagon Injection) | Clinical Grading - Initial Treatment Correct | 84 Hypoglycemic Events |
| Glucose Tabs | Clinical Grading - Initial Treatment Correct | 88 Hypoglycemic Events |
p-value: 0.08Mixed Models Analysis
Post Hoc
Clinical Grading - Limited to Events in Primary Analysis
2 graders, blinded to treatment arm, independently graded each hypoglycemic event as a clinical failure or success based on all available BG concentrations within 1 hour of initial treatment. All BG values, along with corresponding time elapsed since treatment, were reviewed to determine whether the response would be considered a treatment success, in a clinical setting. There were no specific cut points; rather than basing the success criteria on whether the BG was above specific cutpoints by specific times, the grader decided whether the event would be considered a success in a clinical setting (i.e. if the BG increased after treatment and reached and maintained a satisfactory level after the treatment). The graders to achieve a consensus grading adjudicated discordant gradings (6% of events). The number of events graded as a treatment success were reported out of the total number of hypoglycemic events, for each treatment arm.
Time frame: 60 minutes
Population: Analysis was limited to hypoglycemic events included in the primary analysis. 3 hypoglycemic events were deemed Indeterminate by the graders during the glucagon period.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| G-Pen Mini™ (Glucagon Injection) | Clinical Grading - Limited to Events in Primary Analysis | 57 Hypoglycemic Events |
| Glucose Tabs | Clinical Grading - Limited to Events in Primary Analysis | 54 Hypoglycemic Events |
p-value: 0.93Mixed Models Analysis