Congenital Hyperinsulinism
Conditions
Brief summary
The objective of the trial is to evaluate the efficacy and safety of dasiglucagon administered as a subcutaneous (SC) infusion in reducing hypoglycemia in children with CHI.
Interventions
DRUGDasiglucagon
Glucagon analog
OTHERStandard of Care
Standard of care according to site and/or country
Sponsors
Zealand Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Months to 12 Years
Healthy volunteers
No
Inclusion criteria
* Established and documented diagnosis of CHI based on standard of care * Experiencing ≥3 events of hypoglycemia per week (plasma glucose \[PG\] \<70 mg/dL \[\<3.9 mmol/L\]) according to the investigator's evaluation * Previously undergone near-total pancreatectomy or being treated with a non-surgical approach, having been evaluated as not eligible for pancreatic surgery * If somatostatin analogues or sirolimus are used, the therapy should be well established as judged by the investigator, especially when considering their biological half-life
Exclusion criteria
* Previous administration of dasiglucagon * Known or suspected allergy to the trial drug or related products * Previous participation (randomization) in this trial * Circulatory instability requiring supportive medication or presence of pheochromocytoma * Requires exogenous insulin * Body weight of \<4 kg (8.8 lbs.) * Documented HbA1c ≥7% subsequent to near-total pancreatectomy and within 6 months prior to screening * Known or suspected presence of significant central nervous system disease/injury such that in the investigator's opinion will affect trial participation * Use of systemic corticosteroids, e.g., hydrocortisone \>20 mg/m2 body surface area or equivalent in the 5 days before screening * Use of anti-inflammatory biological agents, or other immune modulating agents in the 3 months prior to screening * Any clinically significant abnormality identified on echocardiogram that in the opinion of the investigator would affect the patient's ability to participate in the trial * Any recognized clotting or bleeding disorders * Has participated in an interventional clinical trial (investigational or marketed product) within 3 months of screening or 5 half-lives of the drug under investigation (whichever comes first), or plans to participate in another clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hypoglycemia Episode Rate | Baseline, Week 2-4 (Treatment Period 1) | Hypoglycemia episode rate, defined as average weekly number of hypoglycemic episodes (PG \<70 mg/dL \[3.9 mmol/L\]) during Weeks 2-4 as detected by self-monitored plasma glucose (SMPG). The Week 2-4 value is the average weekly number of hypoglycemic episodes across the last 3 weeks of the treatment period. The change from Baseline to Week 2-4 is also provided. The Baseline value is the average weekly number of hypoglycemic episodes during the 2-week baseline period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Time in Range 70-180 mg/dL | Baseline, Week 2-4 (Treatment Period 1) | Percent time in range 70-180 mg/dL (3.9-10.0 mmol/L) during Weeks 2-4 as measured by continuous glucose monitoring. The Week 2-4 value is the average weekly percent time in range 70-180 mg/dL across the last 3 weeks of the treatment period. The change from Baseline to Week 2-4 is also provided. The Baseline value was calculated as the average percent time in range during the 14 days before randomization. |
| Clinically Significant Hypoglycemia Episode Rates | Baseline, Week 2-4 (Treatment Period 1) | Clinically significant hypoglycemia episode rates during Weeks 2-4, defined as average weekly number of clinically significant hypoglycemic episodes (PG \<54 mg/dL \[3.0 mmol/L\]), as detected by SMPG. The Week 2-4 value is the average weekly clinically significant hypoglycemia episode rate across the last 3 weeks of the treatment period. The change from Baseline to Week 2-4 is also provided. The Baseline value is the average weekly number of clinically significant hypoglycemic episodes during the 2-week baseline period. |
| Total Amount of Gastric Carbohydrates Administered to Treat Hypoglycemia | Baseline, Week 2-4 (Treatment Period 1) | Total amount of gastric carbohydrates administered via nasogastric tube or gastrostomy per week to treat hypoglycemia. The Week 2-4 value is the average weekly total amount of gastric carbohydrates across the last 3 weeks of treatment period. The change from Baseline to Week 2-4 is also provided. The Baseline value is the value recorded during the 2-week Baseline period. |
| Rate of Gastric Carbohydrates Administrations to Treat Hypoglycemia | Baseline, Week 2-4 (Treatment Period 1) | Rate of gastric carbohydrate administrations via nasogastric tube or gastrostomy per week to treat hypoglycemia, calculated as the number of times gastric carbohydrates were administered to treat hypoglycemia per week. The Week 2-4 value is the average weekly rate of gastric carbohydrate administrations across the last 3 weeks of the treatment period. The change from Baseline to Week 2-4 is also provided. The Baseline value is the value recorded during the 2-week Baseline period. |
| Extent of Hypoglycemia | Baseline, Week 2-4 (Treatment Period 1) | Extent of hypoglycemia (area over the glucose curve \[AOCglucose\] below 70 mg/dL \[3.9 mmol/L\]) and below 54 mg/dL \[3.0 mmol/L\] as measured by continuous glucose monitoring. The extent of hypoglycemia was defined as the AOCglucose under the threshold divided by total duration in hours of CGM measurement. A reduction in this measure indicates a benefit. The Week 2-4 value is the average weekly extent of hypoglycemia below 70 mg/dL and below 54 mg/dL across the last 3 weeks of the treatment period. The change from Baseline to Week 2-4 is also provided. The Baseline value is the value assessed during the 14 days before randomization. |
| Amount of Nightly Gastric Carbohydrates Administered | Baseline, Week 2-4 (Treatment Period 1) | Amount of nightly (midnight to 6 am) gastric carbohydrates administered via nasogastric tube or gastrostomy per week. The change from Baseline is also provided for each week. The Baseline value is the value recorded during the 2-week Baseline period. |
| Increase in Fasting Tolerance | Baseline, Week 2-4 (Treatment Period 1) | Increase in fasting tolerance (time from beginning of meal to the beginning of the first continuous 15-minute continuous glucose monitoring reading \<70 mg/dL \[3.9 mmol/L\]), or the time the test ended if a continuous 15-minute CGM reading \<70 mg/dL was not reached. The change from Baseline to the End of Treatment Period 1 (Week 4) is also provided. The Baseline value is the value recorded at the Screening visit. |
| Percent Time in Hypoglycemia | Baseline, Week 2-4 (Treatment Period 1) | Percent time in hypoglycemia (PG \<70 mg/dL \[3.9 mmol/L\]) as measured by continuous glucose monitoring. The Week 2-4 value is the average weekly percent of time in hypoglycemia across the last 3 weeks of the treatment period. The change from Baseline to Week 2-4 is also provided. The Baseline value is the value assessed during the 14 days before randomization. |
| Rate of Hypoglycemic Episodes | Baseline, Week 2-4 (Treatment Period 1) | Rate of hypoglycemic episodes, defined as number of episodes with PG \<70 mg/dL (3.9 mmol/L) for 15 minutes or more per week, as measured by continuous glucose monitoring. The Week 2-4 value is the average weekly number of hypoglycemic episodes across the last 3 weeks of the treatment period. The change from Baseline to Week 2-4 is also provided. The Baseline value is the average weekly number of hypoglycemic episodes during the 14 days before randomization. |
| Percent Time in Hypoglycemia in Treatment Period 2 | Baseline, Week 6-8 (Treatment Period 2) | Percent time in hypoglycemia (PG \<70 mg/dL \[3.9 mmol/L\]) as measured by continuous glucose monitoring. The Week 6-8 value is the average weekly percent of time in hypoglycemia across the last 3 weeks of the treatment period. The change from Baseline to Week 6-8 is also provided. The Baseline value is the value assessed during the 14 days before randomization. |
| Rate of Gastric Carbohydrates Administrations to Treat Hypoglycemia in Treatment Period 2 | Baseline, Week 6-8 (Treatment Period 2) | Rate of gastric carbohydrate administrations via nasogastric tube or gastrostomy per week to treat hypoglycemia, calculated as the number of times gastric carbohydrates were administered to treat hypoglycemia per week. The Week 6-8 value is the average weekly rate of gastric carbohydrate administrations across the last 3 weeks of the treatment period. The change from Baseline to Week 6-8 is also provided. The Baseline value is the value recorded during the 2-week Baseline period. |
| Rate of Hypoglycemic Episodes in Treatment Period 2 | Baseline, Week 6-8 (Treatment Period 2) | Hypoglycemia episode rate, defined as average weekly number of hypoglycemic episodes (PG \<70 mg/dL \[3.9 mmol/L\]) as detected by SMPG. The Week 6-8 value is the average weekly number of hypoglycemic episodes across the last 3 weeks of the treatment period. The change from Baseline to Week 6-8 is also provided. The Baseline value is the average weekly number of hypoglycemic episodes during the 2-week baseline period. |
| Rate of Clinically Significant Hypoglycemia Episodes in Treatment Period 2 | Baseline, Week 6-8 (Treatment Period 2) | Change from Baseline to Week 6-8 in the clinically significant (CS) hypoglycemia episode rate in treatment period 2, defined as the average weekly number of episodes \<54 mg/dL (3.0 mmol/L), for 15 minutes or more, as measured by continuous glucose monitoring (CGM). The Week 6-8 value is the average weekly CS hypoglycemia episode rate across the last 3 weeks of the treatment period. The Baseline value is the average weekly number of CS hypoglycemic episodes during the 14 days before randomization. |
| Total Amount of Gastric Carbohydrates Administered | Baseline, Week 2-4 (Treatment Period 1) | Total amount of gastric carbohydrates administered (regardless of whether this was to treat hypoglycemia or not) via nasogastric tube or gastrostomy per week. The Week 2-4 value is the average amount of gastric carbohydrates administered via nasogastric tube or gastrostomy across the last 3 weeks of the treatment period. The change from baseline to Week 2-4 is also provided. The baseline value is the value recorded during the 2-week baseline period. |
Countries
Germany, Israel, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard of Care + Dasiglucagon 4 weeks (Treatment Period 1) + 4 weeks (Treatment Period 2) of dasiglucagon treatment as an SC infusion starting at 10 µg/hr on top of standard of care
Dasiglucagon: Glucagon analog
Standard of care: Standard of care according to site and/or country | 16 |
| Standard of Care Only 4 weeks (Treatment Period 1) of standard of care + 4 weeks (Treatment Period 2) of dasiglucagon treatment as an SC infusion starting at 10 µg/hr on top of standard of care
Dasiglucagon: Glucagon analog
Standard of care: Standard of care according to site and/or country | 16 |
| Total | 32 |
Baseline characteristics
| Characteristic | Standard of Care Only | Standard of Care + Dasiglucagon | Total |
|---|---|---|---|
| Age, Continuous | 5.00 years STANDARD_DEVIATION 2.892 | 3.55 years STANDARD_DEVIATION 2.592 | 4.27 years STANDARD_DEVIATION 2.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 4 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 12 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Gastrostomy/nasogastric tube Gastrostomy | 12 Participants | 9 Participants | 21 Participants |
| Gastrostomy/nasogastric tube Nasogastric tube | 1 Participants | 2 Participants | 3 Participants |
| Gastrostomy/nasogastric tube None | 3 Participants | 5 Participants | 8 Participants |
| Region of Enrollment Germany | 3 participants | 3 participants | 6 participants |
| Region of Enrollment Israel | 3 participants | 0 participants | 3 participants |
| Region of Enrollment United Kingdom | 3 participants | 6 participants | 9 participants |
| Region of Enrollment United States | 7 participants | 7 participants | 14 participants |
| Sex: Female, Male Female | 10 Participants | 6 Participants | 16 Participants |
| Sex: Female, Male Male | 6 Participants | 10 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 | 0 / 32 |
| other Total, other adverse events | 14 / 16 | 8 / 16 | 24 / 32 |
| serious Total, serious adverse events | 2 / 16 | 1 / 16 | 2 / 32 |
Outcome results
Primary
Hypoglycemia Episode Rate
Hypoglycemia episode rate, defined as average weekly number of hypoglycemic episodes (PG \<70 mg/dL \[3.9 mmol/L\]) during Weeks 2-4 as detected by self-monitored plasma glucose (SMPG). The Week 2-4 value is the average weekly number of hypoglycemic episodes across the last 3 weeks of the treatment period. The change from Baseline to Week 2-4 is also provided. The Baseline value is the average weekly number of hypoglycemic episodes during the 2-week baseline period.
Time frame: Baseline, Week 2-4 (Treatment Period 1)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care + Dasiglucagon | Hypoglycemia Episode Rate | Weekly number of episodes in Weeks 2-4 | 5.29 episodes per week | Standard Deviation 5.256 |
| Standard of Care + Dasiglucagon | Hypoglycemia Episode Rate | Change from Baseline | -3.05 episodes per week | Standard Deviation 4.343 |
| Standard of Care Only | Hypoglycemia Episode Rate | Weekly number of episodes in Weeks 2-4 | 5.85 episodes per week | Standard Deviation 2.767 |
| Standard of Care Only | Hypoglycemia Episode Rate | Change from Baseline | -3.15 episodes per week | Standard Deviation 4.753 |
Comparison: The primary analysis was performed as a negative binominal regression analysis on the difference of the SMPG-detected hypoglycemia episode rate between treatment groups over the Weeks 2-4.p-value: 0.502895% CI: [0.54, 1.36]Negative binomial regression
Secondary
Amount of Nightly Gastric Carbohydrates Administered
Amount of nightly (midnight to 6 am) gastric carbohydrates administered via nasogastric tube or gastrostomy per week. The change from Baseline is also provided for each week. The Baseline value is the value recorded during the 2-week Baseline period.
Time frame: Baseline, Week 2-4 (Treatment Period 1)
Population: The total amount of gastric carbohydrates administered to treat hypoglycemia could be evaluated only in patients with gastrostomy or NG-tube at screening, and is summarized accordingly.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care + Dasiglucagon | Amount of Nightly Gastric Carbohydrates Administered | Week 1 | 95.98 grams | Standard Deviation 153.272 |
| Standard of Care + Dasiglucagon | Amount of Nightly Gastric Carbohydrates Administered | Change from Baseline at Week 1 | 41.64 grams | Standard Deviation 63.484 |
| Standard of Care + Dasiglucagon | Amount of Nightly Gastric Carbohydrates Administered | Week 2 | 77.24 grams | Standard Deviation 147.065 |
| Standard of Care + Dasiglucagon | Amount of Nightly Gastric Carbohydrates Administered | Change from Baseline at Week 2 | 22.90 grams | Standard Deviation 137.325 |
| Standard of Care + Dasiglucagon | Amount of Nightly Gastric Carbohydrates Administered | Week 3 | 67.59 grams | Standard Deviation 141.062 |
| Standard of Care + Dasiglucagon | Amount of Nightly Gastric Carbohydrates Administered | Change from Baseline at Week 3 | 13.24 grams | Standard Deviation 148.569 |
| Standard of Care + Dasiglucagon | Amount of Nightly Gastric Carbohydrates Administered | Week 4 | 63.89 grams | Standard Deviation 127.849 |
| Standard of Care + Dasiglucagon | Amount of Nightly Gastric Carbohydrates Administered | Change from Baseline at Week 4 | 9.55 grams | Standard Deviation 134.369 |
| Standard of Care Only | Amount of Nightly Gastric Carbohydrates Administered | Change from Baseline at Week 4 | 4.83 grams | Standard Deviation 25.689 |
| Standard of Care Only | Amount of Nightly Gastric Carbohydrates Administered | Week 1 | 33.43 grams | Standard Deviation 90.955 |
| Standard of Care Only | Amount of Nightly Gastric Carbohydrates Administered | Week 3 | 30.31 grams | Standard Deviation 94.87 |
| Standard of Care Only | Amount of Nightly Gastric Carbohydrates Administered | Change from Baseline at Week 1 | 3.64 grams | Standard Deviation 27.29 |
| Standard of Care Only | Amount of Nightly Gastric Carbohydrates Administered | Week 4 | 34.62 grams | Standard Deviation 94.549 |
| Standard of Care Only | Amount of Nightly Gastric Carbohydrates Administered | Week 2 | 39.25 grams | Standard Deviation 100.638 |
| Standard of Care Only | Amount of Nightly Gastric Carbohydrates Administered | Change from Baseline at Week 3 | 0.52 grams | Standard Deviation 25.022 |
| Standard of Care Only | Amount of Nightly Gastric Carbohydrates Administered | Change from Baseline at Week 2 | 9.46 grams | Standard Deviation 40.853 |
Secondary
Clinically Significant Hypoglycemia Episode Rates
Clinically significant hypoglycemia episode rates during Weeks 2-4, defined as average weekly number of clinically significant hypoglycemic episodes (PG \<54 mg/dL \[3.0 mmol/L\]), as detected by SMPG. The Week 2-4 value is the average weekly clinically significant hypoglycemia episode rate across the last 3 weeks of the treatment period. The change from Baseline to Week 2-4 is also provided. The Baseline value is the average weekly number of clinically significant hypoglycemic episodes during the 2-week baseline period.
Time frame: Baseline, Week 2-4 (Treatment Period 1)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care + Dasiglucagon | Clinically Significant Hypoglycemia Episode Rates | Weekly number of episodes in Weeks 2-4 | 1.77 episodes per week | Standard Deviation 1.857 |
| Standard of Care + Dasiglucagon | Clinically Significant Hypoglycemia Episode Rates | Change from Baseline | -0.51 episodes per week | Standard Deviation 2.798 |
| Standard of Care Only | Clinically Significant Hypoglycemia Episode Rates | Weekly number of episodes in Weeks 2-4 | 1.90 episodes per week | Standard Deviation 1.407 |
| Standard of Care Only | Clinically Significant Hypoglycemia Episode Rates | Change from Baseline | -0.35 episodes per week | Standard Deviation 1.446 |
p-value: 0.811495% CI: [0.49, 1.74]Negative binominal regression
Secondary
Extent of Hypoglycemia
Extent of hypoglycemia (area over the glucose curve \[AOCglucose\] below 70 mg/dL \[3.9 mmol/L\]) and below 54 mg/dL \[3.0 mmol/L\] as measured by continuous glucose monitoring. The extent of hypoglycemia was defined as the AOCglucose under the threshold divided by total duration in hours of CGM measurement. A reduction in this measure indicates a benefit. The Week 2-4 value is the average weekly extent of hypoglycemia below 70 mg/dL and below 54 mg/dL across the last 3 weeks of the treatment period. The change from Baseline to Week 2-4 is also provided. The Baseline value is the value assessed during the 14 days before randomization.
Time frame: Baseline, Week 2-4 (Treatment Period 1)
Population: There was 1 missing value at Baseline for the dasiglucagon + standard of care group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care + Dasiglucagon | Extent of Hypoglycemia | Week 2-4: Extent of Hypoglycemia Below 70 mg/dL (3.9 mmol/L) | 0.083 mmol/L | Standard Deviation 0.0618 |
| Standard of Care + Dasiglucagon | Extent of Hypoglycemia | Change from Baseline in Extent of Hypoglycemia Below 70 mg/dL (3.9 mmol/L) | -0.062 mmol/L | Standard Deviation 0.1003 |
| Standard of Care + Dasiglucagon | Extent of Hypoglycemia | Week 2-4: Extent of Hypoglycemia Below 54 mg/dL (3.0 mmol/L) | 0.015 mmol/L | Standard Deviation 0.0117 |
| Standard of Care + Dasiglucagon | Extent of Hypoglycemia | Change from Baseline in Extent of Hypoglycemia Below 54 mg/dL (3.0 mmol/L) | -0.008 mmol/L | Standard Deviation 0.0252 |
| Standard of Care Only | Extent of Hypoglycemia | Change from Baseline in Extent of Hypoglycemia Below 54 mg/dL (3.0 mmol/L) | -0.007 mmol/L | Standard Deviation 0.0252 |
| Standard of Care Only | Extent of Hypoglycemia | Week 2-4: Extent of Hypoglycemia Below 70 mg/dL (3.9 mmol/L) | 0.147 mmol/L | Standard Deviation 0.0736 |
| Standard of Care Only | Extent of Hypoglycemia | Week 2-4: Extent of Hypoglycemia Below 54 mg/dL (3.0 mmol/L) | 0.025 mmol/L | Standard Deviation 0.0132 |
| Standard of Care Only | Extent of Hypoglycemia | Change from Baseline in Extent of Hypoglycemia Below 70 mg/dL (3.9 mmol/L) | -0.019 mmol/L | Standard Deviation 0.0959 |
Secondary
Increase in Fasting Tolerance
Increase in fasting tolerance (time from beginning of meal to the beginning of the first continuous 15-minute continuous glucose monitoring reading \<70 mg/dL \[3.9 mmol/L\]), or the time the test ended if a continuous 15-minute CGM reading \<70 mg/dL was not reached. The change from Baseline to the End of Treatment Period 1 (Week 4) is also provided. The Baseline value is the value recorded at the Screening visit.
Time frame: Baseline, Week 2-4 (Treatment Period 1)
Population: There were 2 missing values at the end of Treatment Period 1 in the dasiglucagon + standard of care group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care + Dasiglucagon | Increase in Fasting Tolerance | End of Treatment Period 1 | 6.13 hours | Standard Deviation 5.335 |
| Standard of Care + Dasiglucagon | Increase in Fasting Tolerance | Change from Baseline | 1.20 hours | Standard Deviation 5.908 |
| Standard of Care Only | Increase in Fasting Tolerance | End of Treatment Period 1 | 4.22 hours | Standard Deviation 4.222 |
| Standard of Care Only | Increase in Fasting Tolerance | Change from Baseline | 1.27 hours | Standard Deviation 3.836 |
p-value: 0.643395% CI: [-2.71, 4.39]ANCOVA
Secondary
Percent Time in Hypoglycemia
Percent time in hypoglycemia (PG \<70 mg/dL \[3.9 mmol/L\]) as measured by continuous glucose monitoring. The Week 2-4 value is the average weekly percent of time in hypoglycemia across the last 3 weeks of the treatment period. The change from Baseline to Week 2-4 is also provided. The Baseline value is the value assessed during the 14 days before randomization.
Time frame: Baseline, Week 2-4 (Treatment Period 1)
Population: There was 1 missing value at Baseline for the dasiglucagon + standard of care group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care + Dasiglucagon | Percent Time in Hypoglycemia | Week 2-4 | 11.77 percent time | Standard Deviation 9.248 |
| Standard of Care + Dasiglucagon | Percent Time in Hypoglycemia | Change from Baseline | -9.91 percent time | Standard Deviation 10.119 |
| Standard of Care Only | Percent Time in Hypoglycemia | Week 2-4 | 20.22 percent time | Standard Deviation 10.034 |
| Standard of Care Only | Percent Time in Hypoglycemia | Change from Baseline | -1.95 percent time | Standard Deviation 10.186 |
Secondary
Percent Time in Hypoglycemia in Treatment Period 2
Percent time in hypoglycemia (PG \<70 mg/dL \[3.9 mmol/L\]) as measured by continuous glucose monitoring. The Week 6-8 value is the average weekly percent of time in hypoglycemia across the last 3 weeks of the treatment period. The change from Baseline to Week 6-8 is also provided. The Baseline value is the value assessed during the 14 days before randomization.
Time frame: Baseline, Week 6-8 (Treatment Period 2)
Population: There was 1 participant with a missing value at Baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care + Dasiglucagon | Percent Time in Hypoglycemia in Treatment Period 2 | Week 6-8 | 8.64 percent time | Standard Deviation 6.011 |
| Standard of Care + Dasiglucagon | Percent Time in Hypoglycemia in Treatment Period 2 | Change from Baseline | -13.27 percent time | Standard Deviation 10.12 |
Secondary
Percent Time in Range 70-180 mg/dL
Percent time in range 70-180 mg/dL (3.9-10.0 mmol/L) during Weeks 2-4 as measured by continuous glucose monitoring. The Week 2-4 value is the average weekly percent time in range 70-180 mg/dL across the last 3 weeks of the treatment period. The change from Baseline to Week 2-4 is also provided. The Baseline value was calculated as the average percent time in range during the 14 days before randomization.
Time frame: Baseline, Week 2-4 (Treatment Period 1)
Population: There was 1 missing value at Baseline for the dasiglucagon + standard of care group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care + Dasiglucagon | Percent Time in Range 70-180 mg/dL | Week 2-4 | 75.10 percent time | Standard Deviation 11.821 |
| Standard of Care + Dasiglucagon | Percent Time in Range 70-180 mg/dL | Change from Baseline | -0.97 percent time | Standard Deviation 11.837 |
| Standard of Care Only | Percent Time in Range 70-180 mg/dL | Week 2-4 | 72.65 percent time | Standard Deviation 7.313 |
| Standard of Care Only | Percent Time in Range 70-180 mg/dL | Change from Baseline | 2.44 percent time | Standard Deviation 9.584 |
p-value: 0.965395% CI: [-6.48, 6.78]ANCOVA
Secondary
Rate of Clinically Significant Hypoglycemia Episodes in Treatment Period 2
Change from Baseline to Week 6-8 in the clinically significant (CS) hypoglycemia episode rate in treatment period 2, defined as the average weekly number of episodes \<54 mg/dL (3.0 mmol/L), for 15 minutes or more, as measured by continuous glucose monitoring (CGM). The Week 6-8 value is the average weekly CS hypoglycemia episode rate across the last 3 weeks of the treatment period. The Baseline value is the average weekly number of CS hypoglycemic episodes during the 14 days before randomization.
Time frame: Baseline, Week 6-8 (Treatment Period 2)
Population: There was 1 participant with a missing value at Baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care + Dasiglucagon | Rate of Clinically Significant Hypoglycemia Episodes in Treatment Period 2 | Week 6-8 | 7.78 episodes per week | Standard Deviation 5.226 |
| Standard of Care + Dasiglucagon | Rate of Clinically Significant Hypoglycemia Episodes in Treatment Period 2 | Change from Baseline | -8.51 episodes per week | Standard Deviation 9.941 |
Secondary
Rate of Gastric Carbohydrates Administrations to Treat Hypoglycemia
Rate of gastric carbohydrate administrations via nasogastric tube or gastrostomy per week to treat hypoglycemia, calculated as the number of times gastric carbohydrates were administered to treat hypoglycemia per week. The Week 2-4 value is the average weekly rate of gastric carbohydrate administrations across the last 3 weeks of the treatment period. The change from Baseline to Week 2-4 is also provided. The Baseline value is the value recorded during the 2-week Baseline period.
Time frame: Baseline, Week 2-4 (Treatment Period 1)
Population: The total amount of gastric carbohydrates administered to treat hypoglycemia could be evaluated only in patients with gastrostomy or NG-tube at screening, and is summarized accordingly.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care + Dasiglucagon | Rate of Gastric Carbohydrates Administrations to Treat Hypoglycemia | Week 2-4 | 2.30 number of administrations per week | Standard Deviation 3.433 |
| Standard of Care + Dasiglucagon | Rate of Gastric Carbohydrates Administrations to Treat Hypoglycemia | Change from Baseline | -0.29 number of administrations per week | Standard Deviation 4.92 |
| Standard of Care Only | Rate of Gastric Carbohydrates Administrations to Treat Hypoglycemia | Week 2-4 | 2.18 number of administrations per week | Standard Deviation 2.714 |
| Standard of Care Only | Rate of Gastric Carbohydrates Administrations to Treat Hypoglycemia | Change from Baseline | -2.13 number of administrations per week | Standard Deviation 3.825 |
Secondary
Rate of Gastric Carbohydrates Administrations to Treat Hypoglycemia in Treatment Period 2
Rate of gastric carbohydrate administrations via nasogastric tube or gastrostomy per week to treat hypoglycemia, calculated as the number of times gastric carbohydrates were administered to treat hypoglycemia per week. The Week 6-8 value is the average weekly rate of gastric carbohydrate administrations across the last 3 weeks of the treatment period. The change from Baseline to Week 6-8 is also provided. The Baseline value is the value recorded during the 2-week Baseline period.
Time frame: Baseline, Week 6-8 (Treatment Period 2)
Population: The total amount of gastric carbohydrates administered to treat hypoglycemia could be evaluated only in patients with gastrostomy or NG-tube at screening, and is summarized accordingly.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care + Dasiglucagon | Rate of Gastric Carbohydrates Administrations to Treat Hypoglycemia in Treatment Period 2 | Week 6-8 | 1.31 number of administrations per week | Standard Deviation 2.254 |
| Standard of Care + Dasiglucagon | Rate of Gastric Carbohydrates Administrations to Treat Hypoglycemia in Treatment Period 2 | Change from Baseline | -2.22 number of administrations per week | Standard Deviation 4.99 |
Secondary
Rate of Hypoglycemic Episodes
Rate of hypoglycemic episodes, defined as number of episodes with PG \<70 mg/dL (3.9 mmol/L) for 15 minutes or more per week, as measured by continuous glucose monitoring. The Week 2-4 value is the average weekly number of hypoglycemic episodes across the last 3 weeks of the treatment period. The change from Baseline to Week 2-4 is also provided. The Baseline value is the average weekly number of hypoglycemic episodes during the 14 days before randomization.
Time frame: Baseline, Week 2-4 (Treatment Period 1)
Population: There was 1 missing value at Baseline for the dasiglucagon + standard of care group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care + Dasiglucagon | Rate of Hypoglycemic Episodes | Week 2-4 | 21.71 episodes per week | Standard Deviation 14.179 |
| Standard of Care + Dasiglucagon | Rate of Hypoglycemic Episodes | Change from Baseline | -14.37 episodes per week | Standard Deviation 21.184 |
| Standard of Care Only | Rate of Hypoglycemic Episodes | Week 2-4 | 36.88 episodes per week | Standard Deviation 15.023 |
| Standard of Care Only | Rate of Hypoglycemic Episodes | Change from Baseline | -6.28 episodes per week | Standard Deviation 20.565 |
Secondary
Rate of Hypoglycemic Episodes in Treatment Period 2
Hypoglycemia episode rate, defined as average weekly number of hypoglycemic episodes (PG \<70 mg/dL \[3.9 mmol/L\]) as detected by SMPG. The Week 6-8 value is the average weekly number of hypoglycemic episodes across the last 3 weeks of the treatment period. The change from Baseline to Week 6-8 is also provided. The Baseline value is the average weekly number of hypoglycemic episodes during the 2-week baseline period.
Time frame: Baseline, Week 6-8 (Treatment Period 2)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care + Dasiglucagon | Rate of Hypoglycemic Episodes in Treatment Period 2 | Weekly number of episodes in Weeks 6-8 | 3.06 episodes per week | Standard Deviation 2.73 |
| Standard of Care + Dasiglucagon | Rate of Hypoglycemic Episodes in Treatment Period 2 | Change from Baseline | -5.61 episodes per week | Standard Deviation 4.096 |
Secondary
Total Amount of Gastric Carbohydrates Administered
Total amount of gastric carbohydrates administered (regardless of whether this was to treat hypoglycemia or not) via nasogastric tube or gastrostomy per week. The Week 2-4 value is the average amount of gastric carbohydrates administered via nasogastric tube or gastrostomy across the last 3 weeks of the treatment period. The change from baseline to Week 2-4 is also provided. The baseline value is the value recorded during the 2-week baseline period.
Time frame: Baseline, Week 2-4 (Treatment Period 1)
Population: The total amount of gastric carbohydrates administered to treat hypoglycemia could be evaluated only in patients with gastrostomy or NG-tube at screening, and is summarized accordingly.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care + Dasiglucagon | Total Amount of Gastric Carbohydrates Administered | Week 2-4 | 567.35 grams | Standard Deviation 453.373 |
| Standard of Care + Dasiglucagon | Total Amount of Gastric Carbohydrates Administered | Change from Baseline | -146.56 grams | Standard Deviation 222.995 |
| Standard of Care Only | Total Amount of Gastric Carbohydrates Administered | Week 2-4 | 775.96 grams | Standard Deviation 551.64 |
| Standard of Care Only | Total Amount of Gastric Carbohydrates Administered | Change from Baseline | 160.44 grams | Standard Deviation 438.735 |
Secondary
Total Amount of Gastric Carbohydrates Administered to Treat Hypoglycemia
Total amount of gastric carbohydrates administered via nasogastric tube or gastrostomy per week to treat hypoglycemia. The Week 2-4 value is the average weekly total amount of gastric carbohydrates across the last 3 weeks of treatment period. The change from Baseline to Week 2-4 is also provided. The Baseline value is the value recorded during the 2-week Baseline period.
Time frame: Baseline, Week 2-4 (Treatment Period 1)
Population: The total amount of gastric carbohydrates administered to treat hypoglycemia could be evaluated only in patients with gastrostomy or NG-tube at screening, and is summarized accordingly.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care + Dasiglucagon | Total Amount of Gastric Carbohydrates Administered to Treat Hypoglycemia | Week 2-4 | 22.89 grams | Standard Deviation 31.415 |
| Standard of Care + Dasiglucagon | Total Amount of Gastric Carbohydrates Administered to Treat Hypoglycemia | Change from Baseline | -33.66 grams | Standard Deviation 82.767 |
| Standard of Care Only | Total Amount of Gastric Carbohydrates Administered to Treat Hypoglycemia | Week 2-4 | 37.66 grams | Standard Deviation 57.998 |
| Standard of Care Only | Total Amount of Gastric Carbohydrates Administered to Treat Hypoglycemia | Change from Baseline | -19.74 grams | Standard Deviation 64.082 |