NCT02656069

Safety and Efficacy of G-Pen Compared to Lilly Glucagon for Hypoglycemia Rescue in Adult Type 1 Diabetics

Completed Phase 3 Results posted Last updated 30 October 2018

What this trial tests

Phase 3 trial testing G-Pen (glucagon injection) in Hypoglycemia in 80 participants. Completed in 25 September 2017.

Timeline

15 March 2017

Primary endpoint
14 August 2017

25 September 2017

Quick facts

Lead sponsor	Xeris Pharmaceuticals
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	triple
Primary purpose	treatment
Enrollment	80
Start date	15 March 2017
Primary completion	14 August 2017
Estimated completion	25 September 2017
Sites	7 locations across Canada, United States

Drugs / interventions tested

• G-Pen (glucagon injection) — full drug profile →
• Lilly Glucagon (glucagon injection [rDNA origin]) — full drug profile →

Conditions studied

• Hypoglycemia — all drugs for Hypoglycemia →
• Diabetes Mellitus, Type 1 — all drugs for Diabetes Mellitus, Type 1 →

Sponsor

Xeris Pharmaceuticals — full company profile →

Who can join

Adults 18 to 75, any sex, with Hypoglycemia or Diabetes Mellitus, Type 1. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Hypoglycemia Rescue: Intent-to-Treat Population Primary · At 30 minutes following administration of study drug

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

Group	Value	95% CI
G-Pen	74
Lilly Glucagon	79

Hypoglycemia Rescue: Per Protocol Population Primary · At 30 minutes following administration of study drug

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

Group	Value	95% CI
G-Pen	74
Lilly Glucagon	78

Hypoglycemia Rescue: Alternate Glucose Response Definition Primary · At 30 minutes following administration of study drug

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

Group	Value	95% CI
G-Pen	76
Lilly Glucagon	79

Plasma Glucose Area Under the Curve (AUC) Secondary · At -5, 0, 10, 20, 30, 45, 60, and 90 minutes following administration of glucagon

Pharmacodynamic endpoint of plasma glucose AUC from baseline to 90 minutes following administration of glucagon

Group	Value	95% CI
G-Pen	11651.4	± 2406.9
Lilly Glucagon	12260.4	± 2134.2

Plasma Glucose Maximum Concentration (Cmax) Secondary · At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon

Pharmacodynamic endpoint of plasma glucose Cmax from baseline to 4 hours following administration of glucagon

Group	Value	95% CI
G-Pen	202.7	± 41.8
Lilly Glucagon	193.5	± 42.2

Plasma Glucose Time to Maximum Concentration (Tmax) Secondary · At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon

Pharmacodynamic endpoint of plasma glucose Tmax from baseline to 4 hours following administration of glucagon

Group	Value	95% CI
G-Pen	111.3	± 33.5
Lilly Glucagon	100.4	± 42.7

Plasma Glucose Time to Concentration > 70 mg/dL Secondary · At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon

Pharmacodynamic endpoint of time to achieve a plasma glucose concentration \> 70 mg/dL following administration of glucagon

Group	Value	95% CI
G-Pen	19.9	± 8.5
Lilly Glucagon	14.2	± 4.3

Time to Resolution of Hypoglycemia Symptoms Secondary · 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

Time to resolution of mean autonomic, mean neuroglycopenic and mean total hypoglycemia symptom scores from baseline through 90 minutes following administration of glucagon.

Autonomic Symptoms

Group	Value	95% CI
G-Pen	16.0	± 11.5
Lilly Glucagon	14.2	± 9.4

Neuroglycopenic Symptoms

Group	Value	95% CI
G-Pen	16.7	± 10.2
Lilly Glucagon	14.3	± 9.0

All Symptoms

Group	Value	95% CI
G-Pen	19.8	± 11.7
Lilly Glucagon	17.0	± 8.9

Global Assessment of Hypoglycemia Secondary · 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

Time to resolution of the overall sensation of hypoglycemia following administration of glucagon

Group	Value	95% CI
G-Pen	16.8	± 10.7
Lilly Glucagon	15.7	± 8.3

Hypoglycemia Rescue: Glucose or Symptomatic Response Definition Secondary · At 30 minutes following administration of study drug

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

Group	Value	95% CI
G-Pen	78
Lilly Glucagon	79

Adverse events — posted to ClinicalTrials.gov

Time frame: 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.. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

G-Pen

Serious: 0/78 (0%)

Deaths: 0/78

Lilly Glucagon

Serious: 1/79 (1%)

Deaths: 0/79

Serious adverse events (1 terms)

Reaction	System	G-Pen	Lilly Glucagon
hyperinsulinemic hypoglycemia	Endocrine disorders	—	—

Other adverse events (3 terms — click to expand)

Reaction	System	G-Pen	Lilly Glucagon
Nausea	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Headache	Nervous system disorders	—	—

Most-reported serious reactions: hyperinsulinemic hypoglycemia.

Data from ClinicalTrials.gov NCT02656069 adverse events section.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. 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.
   Christiansen MP, Cummins M, Prestrelski S, Close NC, et al · · 2021 · cited 17× · PMID 34620618 · DOI 10.1136/bmjdrc-2021-002137
2. Systematic Literature Review and Indirect Treatment Comparison of Three Ready-to-Use Glucagon Treatments for Severe Hypoglycemia.
   Giménez M, Khunti K, Matsuhisa M, Chenji S, et al · · 2023 · cited 3× · PMID 37707700 · DOI 10.1007/s13300-023-01466-6