Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as glucagon
Glucagon RTU · 6 trials · 5 indications
The primary endpoint for this study is an evaluation of change in plasma glucose following treatment with G-Pen, with an emphasis on the increase from baseline to 30 minutes post-dosing.
Mean incidence rate of hypoglycemia during and after sessions of moderate to high intensity aerobic exercise in 12-week Outpatient Phase. Incidence rate is defined as the number of hypoglycemic events divided by the total number of qualified exercise sessions, assessed at group level. Qualified exercise session is: (1) confirmed blood glucose of 100-180 mg/dL prior to start of exercise, (2) self-administered study drug no more than 10 min prior to exercise (5 min target), (3) conducted a protocol allowed exercise of moderate to high intensity for at least 30 min and no longer than 75 min, and (4) achieved a target heart rate of 80% of maximum calculated heart rate at least once during session. Exercise sessions were to occur at least 2-3 times per week. Only 1 qualified exercise session/subject/day was included in the analysis (the first if \>1). Hypoglycemic event defined as any hypoglycemic event occurring within 30 (+2) min after completion of a qualified exercise session.
Outpatient Phase: Mean number of hypoglycemic events associated with the qualified exercise sessions, assessed at group level. A qualified exercise session was defined as one were (1) a confirmed blood glucose value of 100-180 mg/dL prior to start of exercise, (2) self-administered the study drug no more than 10 minutes prior to exercise (5 minutes was the target), (3) conducted a protocol allowed exercise for moderate to high intensity for at least 30 minutes and no longer than 75 minutes, and (4) achieved a target heart rate of 80% of maximum calculated heart rate at least once during the session. A hypoglycemic event was defined as any hypoglycemic event occurring during or within 30 (+2) minutes after completion of a qualified exercise session. Exercise sessions were expected to occur at least 2 to 3 times per week. Only 1 qualified exercise session per subject per day was included in the analysis (the first if \>1).
Outpatient Phase: Mean number of qualified exercise sessions, assessed at group level. A qualified exercise session was defined as one were (1) a confirmed blood glucose value of 100-180 mg/dL prior to start of exercise, (2) self-administered the study drug no more than 10 minutes prior to exercise (5 minutes was the target), (3) conducted a protocol allowed exercise for moderate to high intensity for at least 30 minutes and no longer than 75 minutes, and (4) achieved a target heart rate of 80% of maximum calculated heart rate at least once during the session. Exercise sessions were expected to occur at least 2 to 3 times per week. Only 1 qualified exercise session per subject per day was included in the analysis (the first if \>1).
Number of subjects with blood glucose \> 70 mg/dL
Frequency of blood glucose \> 70 mg/dL
Change from baseline in glucose infusion rate (GIR) will be determined for each subject at 24 and 48 hours from the start of blinded treatment. Subjects with a decrease in GIR ≥ 20% at 24 hours, and ≥ 33% at 48 hours will be considered to have had a clinically meaningful treatment response.
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.
A primary endpoint for this study is the prevention of meal provoked hypoglycemia, defined as sensor glucose levels below \<65 mg/dl, comparing study drug to control.
A primary endpoint for this study is prevention of meal provoked hypoglycemia, defined as plasma glucose levels below \<65 mg/dl, comparing study drug to control
| Arm | Type | Description |
|---|---|---|
| G-Pen (glucagon injection) 0.5 mg | EXPERIMENTAL | A single 0.5 mg subcutaneous (SC) injection of G-Pen (glucagon injection) |
| G-Pen (glucagon injection) 1.0 mg | EXPERIMENTAL | A single 1.0 mg subcutaneous (SC) injection of G-Pen (glucagon injection) |
| CRC Phase: Glucagon RTU With Insulin Pump Reduction | EXPERIMENTAL | CRC Phase: 2-arm randomized double-blind crossover, Glucagon RTU Injection 30 microliters of 0.15 mg injection with 50% reduction in the insulin pump |
| CRC Phase: Vehicle for Glucagon RTU With Insulin Pump Reduction | PLACEBO_COMPARATOR | CRC Phase: 2-arm randomized double-blind crossover, Vehicle for Glucagon RTU Injection 30 microliters vehicle with 50% reduction in the insulin pump |
| Outpatient Phase: Glucagon RTU With Insulin Pump Reduction | EXPERIMENTAL | Outpatient Phase: 3-arm randomized comparison (2-arm double-blind, 1-arm open-label), Glucagon RTU Injection 30 microliters of 0.15 mg injection with 50% reduction in the insulin pump (double-blind arm) |
| Outpatient Phase: Vehicle for Glucagon RTU With Insulin Pump Reduction | PLACEBO_COMPARATOR | Outpatient Phase: 3-arm randomized comparison (2-arm double-blind, 1-arm open-label), Vehicle for Glucagon RTU Injection 30 microliters vehicle with 50% reduction in the insulin pump (double-blind arm) |
| Outpatient Phase: Glucagon RTU Without Insulin Pump Reduction | EXPERIMENTAL | Outpatient Phase: 3-arm randomized comparison (2-arm double-blind, 1-arm open-label), Glucagon RTU Injection 30 microliters of 0.15 mg injection without a reduction in the insulin pump (open-label arm) |
| Glucagon RTU (glucagon injection) | EXPERIMENTAL | Glucagon Ready-to-Use (RTU); 60 μL injection (0.3 mg glucagon) |
| Placebo | PLACEBO_COMPARATOR | Non-active vehicle for Glucagon RTU; 60 μL injection |
| CSI-Glucagon (Double-Blind Phase - 2 days) | EXPERIMENTAL | Glucagon solution delivered as a continuous subcutaneous infusion via a patch pump at a starting dosage of 5 mcg/kg/hr. |
| Placebo (Double-Blind Phase - 2 days) | PLACEBO_COMPARATOR | Vehicle solution delivered as a 24-hour continuous subcutaneous infusion via a patch pump. |
| CSI-Glucagon (Open-label Phase - Up to 28 days) | EXPERIMENTAL | Glucagon solution delivered as a continuous subcutaneous infusion via a patch pump at a starting dosage of 5 mcg/kg/hr. |
| Glucagon | EXPERIMENTAL | 1 mg G-Pen™ (glucagon injection) first, followed by 0.5 mg |
| Study drug (glucagon) first, placebo second | OTHER | Each subject will have two mixed meal tolerance tests performed. Each will be randomized to receive either glucagon or matched placebo during the first testing session. A participant could receive 2 doses of the study drug or placebo at each study visit. The opposite treatment will be given during the second testing session after a 1-2 week washout period. Both participants and the study team will be blinded to the intervention being used during each session. |
| Placebo first, study drug (glucagon) second | OTHER | Each subject will have two mixed meal tolerance tests performed. Each will be randomized to receive either glucagon or matched placebo during the first testing session. A participant could receive 2 doses of the study drug or placebo at each study visit. The opposite treatment will be given during the second testing session after a 1-2 week washout period. Both participants and the study team will be blinded to the intervention being used during each session. |
| Name | Type | Description |
|---|---|---|
| Glucagon | DRUG | 0.5 or 1.0 mg of pre-mixed liquid Xeris glucagon delivered via auto-injector |
| Glucagon RTU Injection With Insulin Pump Reduction | DRUG | 0.15 mg injection with 50% pump reduction |
| Vehicle for Glucagon RTU Injection With Insulin Pump Reduction | OTHER | vehicle injection with 50% pump reduction |
| Glugaon RTU Injection Without Insulin Pump Reduction | DRUG | 0.15 mg injection without pump reduction |
| Glucagon RTU | DRUG | Glucagon RTU is a sterile subcutaneous injectable non-aqueous solution formulation supplied in a vial and administered via syringe. |
| Placebo | OTHER | The placebo is a non-active version of Glucagon RTU formulation, containing the same solvent and excipients (i.e., vehicle). |
| Closed loop glucagon pump | DEVICE | a novel closed-loop glucagon system (CLG) incorporating a novel, stable non-aqueous glucagon formulation together with an infusion pump system (Omnipod) guided by real-time continuous glucose monitoring (Dexcom) that is triggered by a hypoglycemia alert algorithm. |
Inclusion Criteria: * diagnosed with T1D for at least 6 months at Screening. * current usage of daily insulin treatment. Exclusion Criteria: * pregnant or nursing * renal insufficiency * hepatic synthetic insufficiency * aspartate or alanine aminotransferase \> 3 times the upper limit of normal *...
Glucagon RTU is an investigational ready-to-use glucagon formulation developed by Xeris Biopharma Holdings, Inc. (ticker XERS) for hypoglycemia and hyperinsulinemic hypoglycemia. It is a small molecule glucagon receptor agonist given without the reconstitution step required for conventional glucagon products. It is in Phase 2 clinical development.
Glucagon RTU is being studied for the treatment and prevention of hypoglycemia, including exercise-induced hypoglycemia in adults with type 1 diabetes and hyperinsulinemic hypoglycemia after bariatric surgery. Both are Phase 2 indications. It is investigational and has not been approved for commercial use.
Glucagon RTU targets the glucagon receptor, or GCGR, acting as an agonist. By activating GCGR, it stimulates hepatic glucose production to raise blood glucose. The target class is agonist, and the compound is a small molecule. ChEMBL lists it under identifier CHEMBL5314341.
Glucagon RTU is developed by Xeris Biopharma Holdings, Inc., which trades under the ticker XERS. Xeris is the sponsor of the Phase 2 clinical program evaluating the ready-to-use glucagon formulation in hypoglycemia and hyperinsulinemic hypoglycemia.
Glucagon RTU is in Phase 2 clinical development. It is investigational and has not been approved by the FDA. Two Phase 2 trials have been completed, and no active trials are currently listed. The program has enrolled a combined total of 62 participants across those completed studies.
Glucagon RTU has been studied in two completed Phase 2 trials. NCT03841526 evaluated it for prevention of exercise-induced hypoglycemia during aerobic exercise in adults with type 1 diabetes in Canada, enrolling 48 participants. NCT03770637 studied it in subjects with hyperinsulinemic hypoglycemia after bariatric surgery in the United States, enrolling 14 participants.