Trial Outcomes & Findings for G-Pen™ Compared to Lilly Glucagon for Hypoglycemia Rescue in Adults With Type 1 Diabetes (NCT NCT03439072)

NCT ID: NCT03439072

Last Updated: 2020-02-17

Results Overview

Increase in plasma glucose concentration from below 50.0 mg/dL to greater than 70.0 mg/dL within 30 minutes after receiving glucagon

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 81 participants
• Primary outcome timeframe: 0 to 30 minutes post dose
• Results posted on: 2020-02-17

Participant Flow

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.

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.

Participant milestones

Measure	G-Pen Followed by Lilly Glucagon 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 \[RNDA Origin\])	Lilly Glucagon Followed by G-Pen 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 \[RNDA Origin\])
Overall Study STARTED	41	40
Overall Study COMPLETED	39	36
Overall Study NOT COMPLETED	2	4

Reasons for withdrawal

Measure	G-Pen Followed by Lilly Glucagon 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 \[RNDA Origin\])	Lilly Glucagon Followed by G-Pen 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 \[RNDA Origin\])
Overall Study Withdrawal by Subject	2	3
Overall Study Physician Decision	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	All Randomized Subjects n=81 Participants A total of 81 subjects met eligibility requirements and were randomized to study treatment.
Age, Continuous	38.2 years STANDARD_DEVIATION 14.6 • n=5 Participants
Sex: Female, Male Female	37 Participants n=5 Participants
Sex: Female, Male Male	44 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	75 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	71 Participants n=5 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment North America	81 participants n=5 Participants

PRIMARY outcome

Timeframe: 0 to 30 minutes post dose

Population: Intent to treat analysis population

Increase in plasma glucose concentration from below 50.0 mg/dL to greater than 70.0 mg/dL within 30 minutes after receiving glucagon

Outcome measures

Measure	G-Pen n=76 Participants G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector	Lilly Glucagon n=78 Participants Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection \[RNDA Origin\])
Number of Subjects With a Positive Glucose Response	76 Participants	78 Participants

SECONDARY outcome

Timeframe: 0 to 180 minutes post dose

Population: Intent-to treat analysis population

Time from administration of glucagon for plasma glucose to rise from below 50.0 mg/dL to above 70.0 mg/dL

Outcome measures

Measure	G-Pen n=76 Participants G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector	Lilly Glucagon n=78 Participants Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection \[RNDA Origin\])
Time for Positive Glucose Response	12.17 minutes Standard Deviation 3.604	8.58 minutes Standard Deviation 2.026

SECONDARY outcome

Timeframe: 0 to 30 minutes post dose

Population: Intent to treat analysis population

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

Outcome measures

Measure	G-Pen n=76 Participants G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector	Lilly Glucagon n=78 Participants Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection \[RNDA Origin\])
Number of Subjects With a Positive Response for the Combination Endpoint: Positive Glucose Response/Positive Glucose Increase	76 Participants	78 Participants

SECONDARY outcome

Timeframe: 0 to 30 minutes post dose

Population: Intent to treat analysis population

Increase in plasma glucose by ≥ 20.0 mg/dL within 30 minutes after receiving glucagon

Outcome measures

Measure	G-Pen n=76 Participants G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector	Lilly Glucagon n=78 Participants Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection \[RNDA Origin\])
Number of Subjects With a Positive Glucose Increase	76 Participants	78 Participants

SECONDARY outcome

Timeframe: 0 to 180 minutes post dose

Population: Intent to treat analysis population

Time from administration of glucagon for plasma glucose to increase by ≥20 mg/dL from baseline

Outcome measures

Measure	G-Pen n=76 Participants G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector	Lilly Glucagon n=78 Participants Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection \[RNDA Origin\])
Time for Positive Glucose Increase	11.36 minutes Standard Deviation 3.345	8.02 minutes Standard Deviation 1.856

SECONDARY outcome

Timeframe: 0 to 30 minutes post dose

Population: Intent to treat analysis population

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.

Outcome measures

Measure	G-Pen n=76 Participants G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector	Lilly Glucagon n=78 Participants Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection \[RNDA Origin\])
Number of Subjects With a Positive Response for the Combination Endpoint: Positive Glucose Response/Relief of Neuroglycopenic Symptoms	76 Participants	78 Participants

SECONDARY outcome

Timeframe: 0 to 30 minutes post dose

Population: Intent to treat analysis population

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.

Outcome measures

Measure	G-Pen n=76 Participants G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector	Lilly Glucagon n=78 Participants Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection \[RNDA Origin\])
Number of Subjects With Relief of Neuroglycopenic Symptoms	74 Participants	77 Participants

SECONDARY outcome

Timeframe: 0 to 180 minutes post dose

Population: Intent to treat analysis population

Time from administration of glucagon to complete resolution of 4 autonomic symptoms of hypoglycemia. Symptoms included: sweating, tremor, palpitations and feeling of nervousness.

Outcome measures

Measure	G-Pen n=76 Participants G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector	Lilly Glucagon n=78 Participants Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection \[RNDA Origin\])
Time to Resolution of Autonomic Symptoms	13.8 minutes Standard Deviation 10.89	12.0 minutes Standard Deviation 7.44

SECONDARY outcome

Timeframe: 0 to 180 minutes post dose

Population: Intent to treat analysis population

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.

Outcome measures

Measure	G-Pen n=76 Participants G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector	Lilly Glucagon n=78 Participants Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection \[RNDA Origin\])
Time to Resolution of Neuroglycopenic Symptoms	14.2 minutes Standard Deviation 15.12	12.2 minutes Standard Deviation 8.85

SECONDARY outcome

Timeframe: 0 to 180 minutes post dose

Population: Intent to treat analysis population

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.

Outcome measures

Measure	G-Pen n=76 Participants G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector	Lilly Glucagon n=78 Participants Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection \[RNDA Origin\])
Time to Resolution of the Feeling of Hypoglycemia	11.6 minutes Standard Deviation 6.45	13.1 minutes Standard Deviation 7.86

SECONDARY outcome

Timeframe: 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.

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

Area under the curve for plasma glucose.

Outcome measures

Measure	G-Pen n=67 Participants G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector	Lilly Glucagon n=67 Participants Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection \[RNDA Origin\])
Glucose AUC	33686.04 mg∙min/dL Standard Deviation 5300.204	33538.60 mg∙min/dL Standard Deviation 5705.219

SECONDARY outcome

Timeframe: 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.

Population: Intent to treat analysis population

Maximum concentration of plasma glucose.

Outcome measures

Measure	G-Pen n=76 Participants G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector	Lilly Glucagon n=78 Participants Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection \[RNDA Origin\])
Glucose Cmax	238.32 mg/dL Standard Deviation 45.626	228.11 mg/dL Standard Deviation 46.567

SECONDARY outcome

Timeframe: 0 to 180 minutes post dose

Population: Intent to treat analysis population

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.

Outcome measures

Measure	G-Pen n=76 Participants G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector	Lilly Glucagon n=78 Participants Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection \[RNDA Origin\])
Glucose Tmax	125.67 minutes Standard Deviation 33.513	113.89 minutes Standard Deviation 31.908

SECONDARY outcome

Timeframe: 0 to 5 minutes pre-dose

Population: Intent to treat analysis population

Time required to prepare and inject glucagon as measured between a "decision to dose" and completion of the injection

Outcome measures

Measure	G-Pen n=76 Participants G-Pen: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector	Lilly Glucagon n=78 Participants Lilly Glucagon: 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection \[RNDA Origin\])
Glucagon Preparation and Administration Time	27.3 seconds Standard Deviation 19.66	97.2 seconds Standard Deviation 45.06

Adverse Events

G-Pen

Serious events: 0 serious events

Other events: 46 other events

Deaths: 0 deaths

Lilly Glucagon

Serious events: 0 serious events

Other events: 34 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	G-Pen n=76 participants at risk 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 n=78 participants at risk 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.
Nervous system disorders Headache	7.9% 6/76 • Adverse events were collected for up to 9 weeks, from the time of consent through the follow-up visit. 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.	5.1% 4/78 • Adverse events were collected for up to 9 weeks, from the time of consent through the follow-up visit. 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.
Gastrointestinal disorders Nausea	38.2% 29/76 • Adverse events were collected for up to 9 weeks, from the time of consent through the follow-up visit. 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.	33.3% 26/78 • Adverse events were collected for up to 9 weeks, from the time of consent through the follow-up visit. 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.
Gastrointestinal disorders Vomiting	26.3% 20/76 • Adverse events were collected for up to 9 weeks, from the time of consent through the follow-up visit. 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.	14.1% 11/78 • Adverse events were collected for up to 9 weeks, from the time of consent through the follow-up visit. 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.

Additional Information

Martin J. Cummins

Xeris Pharmaceuticals, Inc.

Phone: 312-736-1624

Email: mcummins@xerispharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER