Hypoglycemia
Conditions
Brief summary
This is an open-label, exploratory pilot study in patients with T1D. The study will involve two daytime clinical research center visits 7-14 days apart. Subjects will receive a single injection of G-Pen™ (glucagon injection) at each visit.
Detailed description
Following eligibility confirmation, each study participant will undergo two episodes of insulin-induced hypoglycemia with plasma glucose \< 50 mg/dL. Both episodes will be treated with a single subcutaneous injection of G-Pen™ glucagon. For the first treatment visit, all subjects will receive a 1 mg dose of G-Pen™ glucagon. The investigator will have discretion to repeat this same dose at the second treatment visit or give a 0.5 mg dose of G-Pen™ glucagon. A follow-up phone call will be conducted 3-7 days following administration of the final dose of study drug as a safety check.
Interventions
DRUGGlucagon
Sponsors
Xeris Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Type 1 diabetes mellitus for at least 24 months
Exclusion criteria
* Pregnant or Lactating * HbA1c \>10.5% at screening * Use of \> 2.0 U/kg total insulin dose per day * Inadequate bilateral venous access in both arms * Renal insufficiency * Congestive heart failure, NYHA class II, III or IV * Active malignancy within 5 years from screening * Major surgical operation within 30 days prior to screening * Seizure or bleeding disorder * Glycogen storage disease * Active substance or alchohol abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Plasma Glucose > 70 mg/dL at 30 Minutes Post-treatment | 0-90 minutes | For 90 minutes following treatment, plasma glucose was measured every 5 minutes, with an increase in plasma glucose to \>70 mg/dL within 30 minutes of treatment being considered a positive response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Plasma Glucose > 70 mg/dL | 0-90 minutes | Following treatment, plasma glucose was measured every 5 minutes. The first such measurement at which plasma glucose concentration was observed to be \>70 mg/dL was reported as the time to response. |
| Time to Resolution of Induced Hypoglycemia Symptoms | 0-30 minutes | Prior to and every 5 minutes after treatment, subjects were asked to rate the severity of each of 8 symptoms on a scale from 1 to 6, with 1 indicating the symptom was absent and 6 indicating the symptom was severe. The sum of the scores for the 8 individual symptoms was reported as the total hypoglycemia symptom score, which ranged from 8-48. The first time point post-treatment at which total hypoglycemia symptom score = 8 (i.e., all symptoms were absent) was considered the time to resolution. One and two subjects were unevaluable for response to the 1 mg and 0.5 mg doses of glucagon, respectively, as they reported no symptoms (i.e., total symptom score = 8) prior to treatment. |
Countries
United States
Participant flow
Recruitment details
A total of 7 adults with type 1 diabetes were recruited at a clinical research center over a period of 1 month.
Pre-assignment details
One subject was given the 1 mg dose of glucagon at both treatment visits, so only 6 subjects received the 0.5 mg dose.
Participants by arm
| Arm | Count |
|---|---|
| G-Pen™ (Glucagon Injection) 1 mg First, Followed by 0.5 mg A 1 mg dose of G-Pen was given at an initial clinic visit. After a 1-2 week wash-out, subjects received a 0.5 mg dose of G-Pen™ at a second visit. | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | G-Pen™ (Glucagon Injection) 1 mg First, Followed by 0.5 mg |
|---|---|
| Age, Continuous | 42 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment United States | 7 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 7 | 2 / 6 |
| serious Total, serious adverse events | 1 / 7 | 0 / 6 |
Outcome results
Primary
Number of Subjects With Plasma Glucose > 70 mg/dL at 30 Minutes Post-treatment
For 90 minutes following treatment, plasma glucose was measured every 5 minutes, with an increase in plasma glucose to \>70 mg/dL within 30 minutes of treatment being considered a positive response.
Time frame: 0-90 minutes
Population: All treated subjects
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glucagon 1 mg | Number of Subjects With Plasma Glucose > 70 mg/dL at 30 Minutes Post-treatment | 7 participants with positive response |
| Glucagon 0.5 mg | Number of Subjects With Plasma Glucose > 70 mg/dL at 30 Minutes Post-treatment | 6 participants with positive response |
Secondary
Time to Plasma Glucose > 70 mg/dL
Following treatment, plasma glucose was measured every 5 minutes. The first such measurement at which plasma glucose concentration was observed to be \>70 mg/dL was reported as the time to response.
Time frame: 0-90 minutes
Population: All treated subjects
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Glucagon 1 mg | Time to Plasma Glucose > 70 mg/dL | 15 minutes |
| Glucagon 0.5 mg | Time to Plasma Glucose > 70 mg/dL | 15 minutes |
Secondary
Time to Resolution of Induced Hypoglycemia Symptoms
Prior to and every 5 minutes after treatment, subjects were asked to rate the severity of each of 8 symptoms on a scale from 1 to 6, with 1 indicating the symptom was absent and 6 indicating the symptom was severe. The sum of the scores for the 8 individual symptoms was reported as the total hypoglycemia symptom score, which ranged from 8-48. The first time point post-treatment at which total hypoglycemia symptom score = 8 (i.e., all symptoms were absent) was considered the time to resolution. One and two subjects were unevaluable for response to the 1 mg and 0.5 mg doses of glucagon, respectively, as they reported no symptoms (i.e., total symptom score = 8) prior to treatment.
Time frame: 0-30 minutes
Population: Subjects with symptoms of hypoglycemia at time of treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Glucagon 1 mg | Time to Resolution of Induced Hypoglycemia Symptoms | 20 minutes |
| Glucagon 0.5 mg | Time to Resolution of Induced Hypoglycemia Symptoms | 27.5 minutes |