Hypoglycemia, Type 1 Diabetes
Conditions
Keywords
Hypoglycemia, Low Blood Sugar, Type 1 Diabetes, Diabetes, T1D
Brief summary
This research study will investigate whether dasiglucagon as a rescue therapy for participants under 6 years of age works and is safe to use. In addition, the study will investigate how dasiglucagon works in the body (pharmacokinetics and pharmacodynamics). Participants will receive 1 single dose as an injection under the skin (subcutaneous, s.c.) into the buttocks. Participants will have 3 visits with the study team. For each participant, the study will last up to 84 days.
Detailed description
This trial will use a single-administration, open-label trial design to assess the ability of a single SC injection of dasiglucagon to increase plasma glucose in pediatric children with T1D with hypoglycemia. A total of 8 children will be included; 4 children receiving a dose of 0.3 mg and 4 children receiving a dose of 0.6 mg. Of the 4 children receiving 0.3 mg, 2 children should preferably be below 2 years at screening. The 2 additional children receiving 0.3 mg should weigh below 15 kg at screening and should preferably be below 4 years at screening. For children receiving the 0.6 mg dose, all must be above 2 years at screening. Before an eligible child is dosed, the dose level (0.6 mg or 0.3 mg) must be confirmed by the sponsor. Each child will be dosed after the safety assessment of the preceding child has been completed and assessed by the Trial Safety Group. The trial will include the following visits: * A screening visit (Visit 1) in the period from Day - 50 to Day - 29 (pre-treatment visit) * A dosing visit (Visit 2), Day 1 (day of single dosing with investigational medicinal product \[IMP\]) * A Safety follow-up visit (Visit 3) at Day 29 +5 days (the end-of-trial visit). The primary endpoint of the trial is plasma glucose change from baseline at 30 minutes after IMP injection or at the time of rescue by intravenous glucose. Pharmacodynamics (PD) i.e., plasma glucose will be assessed at baseline and 15 and 30 minutes after dosing, while the glucose levels will be monitored by continuous glucose monitoring and by a plasma glucose analyzer during the dosing visit (Visit 2). Pharmacokinetics (PK) will be assessed throughout a 300-minute period at the dosing visit (Visit 2). Safety will be assessed prior to dosing and throughout a 300-minute period after dosing and again at the follow-up visit.
Interventions
DRUGDasiglucagon
Dasiglucagon, 0.6 mg/0.6 mL or 0.3 mg/0.3 mL will be administered as an under the skin (subcutaneous, s.c.) injection by a prefilled syringe, into the buttocks.
Sponsors
Novo Nordisk A/S
Zealand Pharma
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 5 Years
Healthy volunteers
No
Inclusion criteria
* Participants who are confirmed as having T1D based on medical history and are receiving daily insulin therapy via insulin pump or MDI * Body weight greater than 8 kg * Child must be \<6 years of age at the time of screening * Further inclusion criteria apply
Exclusion criteria
* Known or suspected allergy to the IMP or related products * Any condition that in the investigators opinion may result in diminished hepatic glycogen stores (e.g., prolonged fasting (more than 24 hours) at Visit 2 * History of anaphylaxis or symptoms of severe systemic allergy (such as angioedema) * History of hypoglycemic events associated with seizures * Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Plasma Glucose Concentration at 30 Minutes After IMP Injection | Baseline, 30 minutes after dosing on Day 1 | Glucose levels were monitored by continuous glucose monitoring and by a plasma glucose analyzer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Plasma Glucose Concentration at 15 Minutes After IMP Injection | Baseline, 15 minutes after dosing on Day 1 | Glucose levels were monitored by continuous glucose monitoring and by a plasma glucose analyzer. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From first dose of study drug up to end of follow up (up to Day 29) | Treatment-emergence was defined as those adverse events (AEs) that occurred after dosing and those existing AEs that worsened during the study. An AE was any untoward medical occurrence in a clinical trial participant, temporally associated with the use of trial intervention, whether or not considered related to the trial intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the trial intervention. |
| Number of Participants Who Received Rescue Intravenous (IV) Glucose Infusion Administration | Within 30 minutes of infusion on Day 1 | — |
| Time to First IV Glucose Infusion Following Treatment With Dasiglucagon | Start of first glucose administration up to 30 minutes post-infusion on Day 1 | Time to first IV glucose infusion (minutes) was defined as Time of start of first glucose administration - Time of administration of study medication. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at 2 centers in the United States.
Pre-assignment details
A total 10 participants were screened of which 2 were screen failures and 8 were enrolled to receive study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Dasiglucagon 0.3 mg Participants received a single dose of 0.3 mg dasiglucagon SC injection on Day 1. | 4 |
| Dasiglucagon 0.6 mg Participants received a single dose of 0.6 mg dasiglucagon SC injection on Day 1. | 4 |
| Total | 8 |
Baseline characteristics
| Characteristic | Dasiglucagon 0.6 mg | Total | Dasiglucagon 0.3 mg |
|---|---|---|---|
| Age, Continuous | 4.0 years STANDARD_DEVIATION 0.82 | 3.3 years STANDARD_DEVIATION 1.16 | 2.5 years STANDARD_DEVIATION 1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 7 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| 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 | 4 Participants | 8 Participants | 4 Participants |
| Sex: Female, Male Female | 1 Participants | 4 Participants | 3 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 / 4 | 0 / 4 |
| other Total, other adverse events | 3 / 4 | 3 / 4 |
| serious Total, serious adverse events | 0 / 4 | 1 / 4 |
Outcome results
Primary
Change From Baseline in Plasma Glucose Concentration at 30 Minutes After IMP Injection
Glucose levels were monitored by continuous glucose monitoring and by a plasma glucose analyzer.
Time frame: Baseline, 30 minutes after dosing on Day 1
Population: Full analysis set (FAS) included all participants of the SAF. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dasiglucagon 0.3 mg | Change From Baseline in Plasma Glucose Concentration at 30 Minutes After IMP Injection | 102.3 milligrams per deciliter (mg/dL) | Standard Deviation 10.72 |
| Dasiglucagon 0.6 mg | Change From Baseline in Plasma Glucose Concentration at 30 Minutes After IMP Injection | 104.3 milligrams per deciliter (mg/dL) | Standard Deviation 14.47 |
Secondary
Change From Baseline in Plasma Glucose Concentration at 15 Minutes After IMP Injection
Glucose levels were monitored by continuous glucose monitoring and by a plasma glucose analyzer.
Time frame: Baseline, 15 minutes after dosing on Day 1
Population: FAS included all participants of the SAF. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dasiglucagon 0.3 mg | Change From Baseline in Plasma Glucose Concentration at 15 Minutes After IMP Injection | 57.3 mg/dL | Standard Deviation 13.84 |
| Dasiglucagon 0.6 mg | Change From Baseline in Plasma Glucose Concentration at 15 Minutes After IMP Injection | 53.3 mg/dL | Standard Deviation 4.04 |
Secondary
Number of Participants Who Received Rescue Intravenous (IV) Glucose Infusion Administration
Time frame: Within 30 minutes of infusion on Day 1
Population: SAF included all participants who were enrolled and received at least 1 dose of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dasiglucagon 0.3 mg | Number of Participants Who Received Rescue Intravenous (IV) Glucose Infusion Administration | 0 Participants |
| Dasiglucagon 0.6 mg | Number of Participants Who Received Rescue Intravenous (IV) Glucose Infusion Administration | 0 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Treatment-emergence was defined as those adverse events (AEs) that occurred after dosing and those existing AEs that worsened during the study. An AE was any untoward medical occurrence in a clinical trial participant, temporally associated with the use of trial intervention, whether or not considered related to the trial intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the trial intervention.
Time frame: From first dose of study drug up to end of follow up (up to Day 29)
Population: SAF included all participants who were enrolled and received at least 1 dose of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dasiglucagon 0.3 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 3 Participants |
| Dasiglucagon 0.6 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 4 Participants |
Secondary
Time to First IV Glucose Infusion Following Treatment With Dasiglucagon
Time to first IV glucose infusion (minutes) was defined as Time of start of first glucose administration - Time of administration of study medication.
Time frame: Start of first glucose administration up to 30 minutes post-infusion on Day 1
Population: SAF included all participants who were enrolled and received at least 1 dose of IMP. Here, Overall Number of Participants Analyzed is '0' because no participants received glucose infusion.