G-Pen™ Compared to Lilly Glucagon for Hypoglycemia Rescue in Adults With Type 1 Diabetes

• ClinicalTrials.gov Identifier: NCT03439072
• Recruitment Status: Completed
• First Posted: February 20, 2018
• Results First Posted: May 30, 2019
• Last Update Posted: February 17, 2020
• Sponsor: Xeris Pharmaceuticals
• Collaborators: SGS S.A.; Integrated Medical Development
• Information provided by (Responsible Party): Xeris Pharmaceuticals

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Single (Participant); Primary Purpose: Treatment
• Conditions: Insulin Hypoglycemia; Type 1 Diabetes Mellitus; Severe Hypoglycemia
• Interventions: Drug: G-Pen; Drug: Lilly Glucagon
• Enrollment: 81

Participant Flow

Recruitment Details	The recruitment period began 08 Jan 2018 and ran through 02 Apr 2018. Subjects were screened for study eligibility at one of the six clinical sites up to 30 days prior to randomization.
Pre-assignment Details	A total of 81 eligible subjects were randomized to treatment. However, two subjects withdrew consent prior to dosing, so the number of subjects exposed to study treatment was 79.

Arm/Group Title	G-Pen Followed by Lilly Glucagon	Lilly Glucagon Followed by G-Pen
Arm/Group Description	1 mg G-Pen at the first treatment visit followed by 1 mg Lilly Glucagon at the second treatment visit G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection [RNDA Origin])	1 mg Lilly Glucagon at the first treatment visit followed by 1 mg G-Pen at the second treatment visit G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection [RNDA Origin])
Period Title: Overall Study
Started	41	40
Completed	39 [1]	36 [2]
Not Completed	2	4
Reason Not Completed
Withdrawal by Subject	2	3
Physician Decision	0	1
[1] 1 subject dropped before G-Pen; another after G-Pen (n=40 G-Pen; N=39 Lilly Glucagon); [2] 1 subject dropped before Lilly Glucagon; 3 others after Lilly Glucagon (N=39 Lilly; N=36 G-Pen)

Baseline Characteristics

Arm/Group Title		All Randomized Subjects
Arm/Group Description		A total of 81 subjects met eligibility requirements and were randomized to study treatment.
Overall Number of Baseline Participants		81
Baseline Analysis Population Description		All randomized subjects
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	81 participants
		38.2 (14.6)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	81 participants
	Female	37 45.7%
	Male	44 54.3%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	81 participants
	Hispanic or Latino	6 7.4%
	Not Hispanic or Latino	75 92.6%
	Unknown or Not Reported	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	81 participants
	American Indian or Alaska Native	0 0.0%
	Asian	6 7.4%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	0 0.0%
	White	71 87.7%
	More than one race	3 3.7%
	Unknown or Not Reported	1 1.2%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
North America	Number Analyzed	81 participants
		81

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With a Positive Glucose Response
Description	Increase in plasma glucose concentration from below 50.0 mg/dL to greater than 70.0 mg/dL within 30 minutes after receiving glucagon
Time Frame	0 to 30 minutes post dose

Outcome Measure Data

Analysis Population Description

Intent to treat analysis population

Arm/Group Title	G-Pen	Lilly Glucagon
Arm/Group Description:	G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector	Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection [RNDA Origin])
Overall Number of Participants Analyzed	76	78
Measure Type: Count of Participants; Unit of Measure: Participants
	76 100.0%	78 100.0%

2. Secondary Outcome

Title	Time for Positive Glucose Response
Description	Time from administration of glucagon for plasma glucose to rise from below 50.0 mg/dL to above 70.0 mg/dL
Time Frame	0 to 180 minutes post dose

Outcome Measure Data

Analysis Population Description

Intent-to treat analysis population

Arm/Group Title	G-Pen	Lilly Glucagon
Arm/Group Description:	G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector	Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection [RNDA Origin])
Overall Number of Participants Analyzed	76	78
Mean (Standard Deviation); Unit of Measure: minutes
	12.17 (3.604)	8.58 (2.026)

3. Secondary Outcome

Title	Number of Subjects With a Positive Response for the Combination Endpoint: Positive Glucose Response/Positive Glucose Increase
Description	A positive response for this endpoint is a return of plasma glucose to > 70 mg/dL or an increase in plasma glucose by ≥20 mg/dL within 30 minutes after receiving glucagon
Time Frame	0 to 30 minutes post dose

Outcome Measure Data

Analysis Population Description

Intent to treat analysis population

Arm/Group Title	G-Pen	Lilly Glucagon
Arm/Group Description:	G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector	Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection [RNDA Origin])
Overall Number of Participants Analyzed	76	78
Measure Type: Count of Participants; Unit of Measure: Participants
	76 100.0%	78 100.0%

4. Secondary Outcome

Title	Number of Subjects With a Positive Glucose Increase
Description	Increase in plasma glucose by ≥ 20.0 mg/dL within 30 minutes after receiving glucagon
Time Frame	0 to 30 minutes post dose

Outcome Measure Data

Analysis Population Description

Intent to treat analysis population

Arm/Group Title	G-Pen	Lilly Glucagon
Arm/Group Description:	G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector	Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection [RNDA Origin])
Overall Number of Participants Analyzed	76	78
Measure Type: Count of Participants; Unit of Measure: Participants
	76 100.0%	78 100.0%

5. Secondary Outcome

Title	Time for Positive Glucose Increase
Description	Time from administration of glucagon for plasma glucose to increase by ≥20 mg/dL from baseline
Time Frame	0 to 180 minutes post dose

Outcome Measure Data

Analysis Population Description

Intent to treat analysis population

Arm/Group Title	G-Pen	Lilly Glucagon
Arm/Group Description:	G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector	Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection [RNDA Origin])
Overall Number of Participants Analyzed	76	78
Mean (Standard Deviation); Unit of Measure: minutes
	11.36 (3.345)	8.02 (1.856)

6. Secondary Outcome

Title	Number of Subjects With a Positive Response for the Combination Endpoint: Positive Glucose Response/Relief of Neuroglycopenic Symptoms
Description	A positive response for this endpoint is a return of plasma glucose to > 70 mg/dL or clearance of all neuroglycopenic symptoms of hypoglycemia within 30 minutes after receiving glucagon. Four symptoms were assessed: dizziness, blurred vision, difficulty in thinking and faintness.
Time Frame	0 to 30 minutes post dose

Outcome Measure Data

Analysis Population Description

Intent to treat analysis population

Arm/Group Title	G-Pen	Lilly Glucagon
Arm/Group Description:	G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector	Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection [RNDA Origin])
Overall Number of Participants Analyzed	76	78
Measure Type: Count of Participants; Unit of Measure: Participants
	76 100.0%	78 100.0%

7. Secondary Outcome

Title	Number of Subjects With Relief of Neuroglycopenic Symptoms
Description	Clearance of all neuroglycopenic symptoms of hypoglycemia within 30 minutes after receiving glucagon. Four symptoms were assessed: dizziness, blurred vision, difficulty in thinking and faintness.
Time Frame	0 to 30 minutes post dose

Outcome Measure Data

Analysis Population Description

Intent to treat analysis population

Arm/Group Title	G-Pen	Lilly Glucagon
Arm/Group Description:	G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector	Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection [RNDA Origin])
Overall Number of Participants Analyzed	76	78
Measure Type: Count of Participants; Unit of Measure: Participants
	74 97.4%	77 98.7%

8. Secondary Outcome

Title	Time to Resolution of Autonomic Symptoms
Description	Time from administration of glucagon to complete resolution of 4 autonomic symptoms of hypoglycemia. Symptoms included: sweating, tremor, palpitations and feeling of nervousness.
Time Frame	0 to 180 minutes post dose

Outcome Measure Data

Analysis Population Description

Intent to treat analysis population

Arm/Group Title	G-Pen	Lilly Glucagon
Arm/Group Description:	G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector	Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection [RNDA Origin])
Overall Number of Participants Analyzed	76	78
Mean (Standard Deviation); Unit of Measure: minutes
	13.8 (10.89)	12.0 (7.44)

9. Secondary Outcome

Title	Time to Resolution of Neuroglycopenic Symptoms
Description	Time from administration of glucagon to complete resolution of 4 neuroglycopenic symptoms of hypoglycemia. Four symptoms were assessed: dizziness, blurred vision, difficulty in thinking and faintness.
Time Frame	0 to 180 minutes post dose

Outcome Measure Data

Analysis Population Description

Intent to treat analysis population

Arm/Group Title	G-Pen	Lilly Glucagon
Arm/Group Description:	G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector	Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection [RNDA Origin])
Overall Number of Participants Analyzed	76	78
Mean (Standard Deviation); Unit of Measure: minutes
	14.2 (15.12)	12.2 (8.85)

10. Secondary Outcome

Title	Time to Resolution of the Feeling of Hypoglycemia
Description	Time from administration of glucagon to resolution of the overall sensation of hypoglycemia. Subjects were asked to answer yes/no to the question, "Do you feel hypoglycemic?" The time point as which the subject first answered "no" was considered the time of resolution.
Time Frame	0 to 180 minutes post dose

Outcome Measure Data

Analysis Population Description

Intent to treat analysis population

Arm/Group Title	G-Pen	Lilly Glucagon
Arm/Group Description:	G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector	Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection [RNDA Origin])
Overall Number of Participants Analyzed	76	78
Mean (Standard Deviation); Unit of Measure: minutes
	11.6 (6.45)	13.1 (7.86)

11. Secondary Outcome

Title	Glucose AUC
Description	Area under the curve for plasma glucose.
Time Frame	0 to 180 minutes post dose - Blood samples for assessment of blood glucose concentration were collected every 5 minutes post-dose to 90 minutes, and then at 120, 150 and 180 minutes post dose.

Outcome Measure Data

Analysis Population Description

Intent to treat analysis population. Due to missing data AUC was only evaluable in 67 subjects per arm.

Arm/Group Title	G-Pen	Lilly Glucagon
Arm/Group Description:	G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector	Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection [RNDA Origin])
Overall Number of Participants Analyzed	67	67
Mean (Standard Deviation); Unit of Measure: mg∙min/dL
	33686.04 (5300.204)	33538.60 (5705.219)

12. Secondary Outcome

Title	Glucose Cmax
Description	Maximum concentration of plasma glucose.
Time Frame	0 to 180 minutes post dose - Blood samples for assessment of blood glucose concentration were collected every 5 minutes post-dose to 90 minutes, and then at 120, 150 and 180 minutes post dose.

Outcome Measure Data

Analysis Population Description

Intent to treat analysis population

Arm/Group Title	G-Pen	Lilly Glucagon
Arm/Group Description:	G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector	Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection [RNDA Origin])
Overall Number of Participants Analyzed	76	78
Mean (Standard Deviation); Unit of Measure: mg/dL
	238.32 (45.626)	228.11 (46.567)

13. Secondary Outcome

Title	Glucose Tmax
Description	Time to maximum concentration of plasma glucose. Blood samples for assessment of blood glucose concentration were collected every 5 minutes post-dose to 90 minutes, and then at 120, 150 and 180 minutes post dose.
Time Frame	0 to 180 minutes post dose

Outcome Measure Data

Analysis Population Description

Intent to treat analysis population

Arm/Group Title	G-Pen	Lilly Glucagon
Arm/Group Description:	G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector	Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection [RNDA Origin])
Overall Number of Participants Analyzed	76	78
Mean (Standard Deviation); Unit of Measure: minutes
	125.67 (33.513)	113.89 (31.908)

14. Secondary Outcome

Title	Glucagon Preparation and Administration Time
Description	Time required to prepare and inject glucagon as measured between a "decision to dose" and completion of the injection
Time Frame	0 to 5 minutes pre-dose

Outcome Measure Data

Analysis Population Description

Intent to treat analysis population

Arm/Group Title	G-Pen	Lilly Glucagon
Arm/Group Description:	G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector	Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection [RNDA Origin])
Overall Number of Participants Analyzed	76	78
Mean (Standard Deviation); Unit of Measure: seconds
	27.3 (19.66)	97.2 (45.06)

Adverse Events

Time Frame	Adverse events were collected for up to 9 weeks, from the time of consent through the follow-up visit.
Adverse Event Reporting Description	Treatment-Emergent Adverse Events Note: Some subjects experienced multiple adverse events. Consequently, the sum of the number of subjects experiencing each individual adverse events is greater than the number of unique subjects experiencing at least one adverse event.
Arm/Group Title	G-Pen	Lilly Glucagon
Arm/Group Description	G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector. Between the 2 arms, a total of 76 subjects received a dose of G-Pen in the study.	Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection [RNDA Origin]). Between the 2 arms, a total of 78 subjects received a dose of Lilly Glucagon in the study.
All-Cause Mortality
	G-Pen	Lilly Glucagon
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/76 (0.00%)	0/78 (0.00%)
Serious Adverse Events
	G-Pen	Lilly Glucagon
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/76 (0.00%)	0/78 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	G-Pen	Lilly Glucagon
	Affected / at Risk (%)	Affected / at Risk (%)
Total	46/76 (60.53%)	34/78 (43.59%)
Gastrointestinal disorders
Nausea * 1	29/76 (38.16%)	26/78 (33.33%)
Vomiting * 1	20/76 (26.32%)	11/78 (14.10%)
Nervous system disorders
Headache * 1	6/76 (7.89%)	4/78 (5.13%)
1 Term from vocabulary, MedDRA 20.0; * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Neither the Institution nor the principal investigator may submit for publication or presentation, the results of this trial without prior written consent of the sponsor.

Results Point of Contact

• Name/Title: Martin J. Cummins
• Organization: Xeris Pharmaceuticals, Inc.
• Phone: 312-736-1624
• EMail: mcummins@xerispharma.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Xeris Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03439072
• Other Study ID Numbers: XSGP-303
• First Submitted: February 13, 2018
• First Posted: February 20, 2018
• Results First Submitted: April 17, 2019
• Results First Posted: May 30, 2019
• Last Update Posted: February 17, 2020