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This is a blinded, randomized crossover study to compare the safety and efficacy of G-Pen (glucagon injection) to Lilly Glucagon (glucagon for injection [rDNA origin]) for hypoglycemia rescue of adult patients with type 1 diabetes.
This is a blinded, randomized, Phase 3 comparative efficacy and safety study in adults with type 1 diabetes. Patients will complete screening procedures up to 60 days before randomization to determine eligibility before enrollment to the treatment phase.
The procedure for evaluating the efficacy of the G-Pen (glucagon injection) consists of inducing hypoglycemia by intravenous administration of regular insulin diluted in normal saline. Each participant will undergo two episodes of insulin-induced hypoglycemia, and in random order will receive 1 mg G-Pen (glucagon injection) during one episode and 1 mg Lilly Glucagon during the other episode. There will be wash out period of 7-28 days between treatment visits.
Blood glucose levels will be monitored post-dosing, with a return of plasma glucose to a concentration > 70 mg/dL within 30 minutes signifying successful hypoglycemia rescue. As a confirmation of efficacy, subjects will complete a questionnaire concerning changes in symptoms of hypoglycemia following treatment with glucagon.
Subjects will return for a follow-up safety visit 3-14 days following administration of the final dose of glucagon.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| G-Pen first, then Lilly Glucagon | Other | A single 1 mg subcutaneous (SC) injection of G-Pen (glucagon injection) with a 7-28 day wash-out, followed by a single 1 mg SC injection of Lilly Glucagon (glucagon injection [rDNA origin]) |
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| Lilly Glucagon first, then G-Pen | Other | A single 1 mg SC injection of Lilly Glucagon (glucagon injection [rDNA origin]) with a 7-28 day wash-out, followed by a single 1 mg SC injection of G-Pen (glucagon injection) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| G-Pen (glucagon injection) | Drug | 1 mg of pre-mixed liquid Xeris glucagon delivered via auto-injector |
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| Measure | Description | Time Frame |
|---|---|---|
| Hypoglycemia Rescue: Intent-to-Treat Population | Number of subjects with an increase in plasma glucose concentration from below 50 mg/dL to greater than 70 mg/dL within 30 minutes after administration of glucagon | At 30 minutes following administration of study drug |
| Hypoglycemia Rescue: Per Protocol Population | Number of subjects with an increase in plasma glucose concentration from below 50 mg/dL to greater than 70 mg/dL within 30 minutes after administration of glucagon | At 30 minutes following administration of study drug |
| Hypoglycemia Rescue: Alternate Glucose Response Definition | Number of subjects with either an increase in plasma glucose concentration from below 50 mg/dL to greater than 70 mg/dL or an increase in from baseline in plasma glucose concentration of at least 20 mg/dL within 30 minutes after administration of glucagon | At 30 minutes following administration of study drug |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma Glucose Area Under the Curve (AUC) | Pharmacodynamic endpoint of plasma glucose AUC from baseline to 90 minutes following administration of glucagon | At -5, 0, 10, 20, 30, 45, 60, and 90 minutes following administration of glucagon |
| Plasma Glucose Maximum Concentration (Cmax) |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35294 | United States | ||
| ProSciento, Inc. |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34620618 | Derived | Christiansen MP, Cummins M, Prestrelski S, Close NC, Nguyen A, Junaidi K. Comparison of a ready-to-use liquid glucagon injection administered by autoinjector to glucagon emergency kit for the symptomatic relief of severe hypoglycemia: two randomized crossover non-inferiority studies. BMJ Open Diabetes Res Care. 2021 Oct;9(1):e002137. doi: 10.1136/bmjdrc-2021-002137. |
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A total of 6 screened and eligible subjects were not randomized to one of the treatment sequences due to closing of the enrollment period.
The recruitment period began 15 March 2017 and ran through 30 June 2017. Subjects were screened for study eligibility at one of the 7 clinical sites up to 60 days prior to randomization.
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| ID | Title | Description |
|---|---|---|
| FG000 | G-Pen First, Then Lilly Glucagon | A single 1 mg subcutaneous (SC) injection of G-Pen™ (glucagon injection) with a 7-28 day wash-out, followed by a single 1 mg SC injection of Lilly Glucagon (glucagon injection [rDNA origin]) G-Pen™ (glucagon injection): 1 mg of pre-mixed liquid Xeris glucagon delivered via auto-injector Lilly Glucagon (glucagon injection [rDNA origin]): 1 mg of Lilly glucagon reconstituted from lyophilized powder |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| First Intervention |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 16, 2017 |
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| Lilly Glucagon (glucagon injection [rDNA origin]) | Drug | 1 mg of Lilly glucagon reconstituted from lyophilized powder |
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Pharmacodynamic endpoint of plasma glucose Cmax from baseline to 4 hours following administration of glucagon |
| At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon |
| Plasma Glucose Time to Maximum Concentration (Tmax) | Pharmacodynamic endpoint of plasma glucose Tmax from baseline to 4 hours following administration of glucagon | At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon |
| Plasma Glucose Time to Concentration > 70 mg/dL | Pharmacodynamic endpoint of time to achieve a plasma glucose concentration > 70 mg/dL following administration of glucagon | At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon |
| Time to Resolution of Hypoglycemia Symptoms | Time to resolution of mean autonomic, mean neuroglycopenic and mean total hypoglycemia symptom scores from baseline through 90 minutes following administration of glucagon. | At 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85 and 90 minutes following administration of glucagon |
| Global Assessment of Hypoglycemia | Time to resolution of the overall sensation of hypoglycemia following administration of glucagon | At 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85 and 90 minutes following administration of glucagon |
| Chula Vista |
| California |
| 91911 |
| United States |
| AMCR Institute | Escondido | California | 92025 | United States |
| Diablo Clinical Research | Walnut Creek | California | 94598 | United States |
| Clinical Trials of Texas, Inc. | San Antonio | Texas | 78229 | United States |
| Rainier Research | Renton | Washington | 98057 | United States |
| LMC Diabetes & Endocrinology | Toronto | Ontario | M4G 3E8 | Canada |
| FG001 | Lilly Glucagon First, Then G-Pen | A single 1 mg SC injection of Lilly Glucagon (glucagon injection [rDNA origin]) with a 7-28 day wash-out, followed by a single 1 mg SC injection of G-Pen™ (glucagon injection) Lilly Glucagon (glucagon injection [rDNA origin]): 1 mg of Lilly glucagon reconstituted from lyophilized powder G-Pen™ (glucagon injection): 1 mg of pre-mixed liquid Xeris glucagon delivered via auto-injector |
| COMPLETED |
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| NOT COMPLETED |
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| Second Intervention |
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All eligible, randomized subjects
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| ID | Title | Description |
|---|---|---|
| BG000 | G-Pen First, Then Lilly Glucagon | A single 1 mg subcutaneous (SC) injection of G-Pen™ (glucagon injection) with a 7-28 day wash-out, followed by a single 1 mg SC injection of Lilly Glucagon (glucagon injection [rDNA origin]) G-Pen™ (glucagon injection): 1 mg of pre-mixed liquid Xeris glucagon delivered via auto-injector Lilly Glucagon (glucagon injection [rDNA origin]): 1 mg of Lilly glucagon reconstituted from lyophilized powder |
| BG001 | Lilly Glucagon First, Then G-Pen | A single 1 mg SC injection of Lilly Glucagon (glucagon injection [rDNA origin]) with a 7-28 day wash-out, followed by a single 1 mg SC injection of G-Pen™ (glucagon injection) Lilly Glucagon (glucagon injection [rDNA origin]): 1 mg of Lilly glucagon reconstituted from lyophilized powder G-Pen™ (glucagon injection): 1 mg of pre-mixed liquid Xeris glucagon delivered via auto-injector |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Hypoglycemia Rescue: Intent-to-Treat Population | Number of subjects with an increase in plasma glucose concentration from below 50 mg/dL to greater than 70 mg/dL within 30 minutes after administration of glucagon | Modified intent-to-treat population of all randomized subjects analyzed by actual treatment received | Posted | Count of Participants | Participants | At 30 minutes following administration of study drug |
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| Primary | Hypoglycemia Rescue: Per Protocol Population | Number of subjects with an increase in plasma glucose concentration from below 50 mg/dL to greater than 70 mg/dL within 30 minutes after administration of glucagon | All randomized, treated subjects without a major protocol violation | Posted | Count of Participants | Participants | At 30 minutes following administration of study drug |
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| Primary | Hypoglycemia Rescue: Alternate Glucose Response Definition | Number of subjects with either an increase in plasma glucose concentration from below 50 mg/dL to greater than 70 mg/dL or an increase in from baseline in plasma glucose concentration of at least 20 mg/dL within 30 minutes after administration of glucagon | Modified intent-to-treat population of all randomized subjects analyzed by actual treatment received | Posted | Count of Participants | Participants | At 30 minutes following administration of study drug |
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| Secondary | Plasma Glucose Area Under the Curve (AUC) | Pharmacodynamic endpoint of plasma glucose AUC from baseline to 90 minutes following administration of glucagon | Modified intent-to-treat population of all randomized subjects analyzed by actual treatment received | Posted | Mean | Standard Deviation | mg*min/dL | At -5, 0, 10, 20, 30, 45, 60, and 90 minutes following administration of glucagon |
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| Secondary | Plasma Glucose Maximum Concentration (Cmax) | Pharmacodynamic endpoint of plasma glucose Cmax from baseline to 4 hours following administration of glucagon | Modified intent-to-treat population of all randomized subjects analyzed by actual treatment received | Posted | Mean | Standard Deviation | mg/dL | At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon |
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| Secondary | Plasma Glucose Time to Maximum Concentration (Tmax) | Pharmacodynamic endpoint of plasma glucose Tmax from baseline to 4 hours following administration of glucagon | Modified intent-to-treat population of all randomized subjects analyzed by actual treatment received | Posted | Mean | Standard Deviation | minutes | At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon |
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| Secondary | Plasma Glucose Time to Concentration > 70 mg/dL | Pharmacodynamic endpoint of time to achieve a plasma glucose concentration > 70 mg/dL following administration of glucagon | Modified intent-to-treat population of all randomized subjects analyzed by actual treatment received | Posted | Mean | Standard Deviation | minutes | At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon |
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| Secondary | Time to Resolution of Hypoglycemia Symptoms | Time to resolution of mean autonomic, mean neuroglycopenic and mean total hypoglycemia symptom scores from baseline through 90 minutes following administration of glucagon. | Modified intent-to-treat population of all randomized subjects analyzed by actual treatment received | Posted | Mean | Standard Deviation | minutes | At 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85 and 90 minutes following administration of glucagon |
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| Secondary | Global Assessment of Hypoglycemia | Time to resolution of the overall sensation of hypoglycemia following administration of glucagon | Modified intent-to-treat population of all randomized subjects analyzed by actual treatment received | Posted | Mean | Standard Deviation | minutes | At 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85 and 90 minutes following administration of glucagon |
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| Post-Hoc | Hypoglycemia Rescue: Glucose or Symptomatic Response Definition | Number of subjects with either an increase in plasma glucose concentration from below 50 mg/dL to greater than 70 mg/dL or resolution of all neuroglycopenic symptoms of hypoglycemia within 30 minutes after administration of glucagon | Modified intent-to-treat population of all randomized subjects analyzed by actual treatment received | Posted | Count of Participants | Participants | At 30 minutes following administration of study drug |
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For the first intervention, treatment emergent adverse events were defined as adverse events occurring at any time after receipt of the first intervention and prior to receipt of the second intervention, 7-28 days later. For the second intervention, treatment emergent adverse events were defined as adverse events occurring at any time after receipt of the second intervention and prior to completion of the follow-up evaluation visit occurring 3-14 days later.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | G-Pen | A single 1 mg subcutaneous (SC) injection of G-Pen™ (glucagon injection) | 0 | 78 | 0 | 78 | 24 | 78 |
| EG001 | Lilly Glucagon | A single 1 mg subcutaneous (SC) injection of Lilly Glucagon | 0 | 79 | 1 | 79 | 16 | 79 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| hyperinsulinemic hypoglycemia | Endocrine disorders | MedDRA (20.0) | Non-systematic Assessment | The evening after receiving Lilly Glucagon 1 mg, a subject had severe hypoglycemia at home requiring 3rd party assistance. An emergency medical technician administered saline. The subject recovered with no sequelae and completed the study. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA (20.0) | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (20.0) | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (20.0) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Martin J. Cummins, VP, Clinical Development | Xeris Pharamaceuticals, Inc. | 806-282-2120 | mcummins@xerispharma.com |
| Aug 31, 2018 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D007003 | Hypoglycemia |
| D003922 | Diabetes Mellitus, Type 1 |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D003920 | Diabetes Mellitus |
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D005934 | Glucagon |
| ID | Term |
|---|---|
| D052336 | Proglucagon |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
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| >=65 years |
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| Male |
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| Hispanic |
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| African American |
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| Other |
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| United Staates |
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