Trial Outcomes & Findings for Safety and Efficacy of G-Pen Compared to Lilly Glucagon for Hypoglycemia Rescue in Adult Type 1 Diabetics (NCT NCT02656069)

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

80 participants

Primary outcome timeframe

At 30 minutes following administration of study drug

Results posted on

2018-10-30

Participant Flow

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.

A total of 6 screened and eligible subjects were not randomized to one of the treatment sequences due to closing of the enrollment period.

Participant milestones

Participant milestones
Measure	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	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
First Intervention STARTED	44	36
First Intervention COMPLETED	44	36
First Intervention NOT COMPLETED	0	0
Second Intervention STARTED	44	36
Second Intervention COMPLETED	43	35
Second Intervention NOT COMPLETED	1	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	G-Pen First, Then Lilly Glucagon n=44 Participants 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	Lilly Glucagon First, Then G-Pen n=36 Participants 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	Total n=80 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	40 Participants n=5 Participants	31 Participants n=7 Participants	71 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Age, Continuous	42.1 years STANDARD_DEVIATION 15.55 • n=5 Participants	45.5 years STANDARD_DEVIATION 14.87 • n=7 Participants	43.6 years STANDARD_DEVIATION 15.25 • n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	15 Participants n=7 Participants	30 Participants n=5 Participants
Sex: Female, Male Male	29 Participants n=5 Participants	21 Participants n=7 Participants	50 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Non-Hispanic White	38 Participants n=5 Participants	29 Participants n=7 Participants	67 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Hispanic	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · African American	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Other	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment North America · Canada	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Region of Enrollment North America · United Staates	40 Participants n=5 Participants	32 Participants n=7 Participants	72 Participants n=5 Participants

PRIMARY outcome

Timeframe: At 30 minutes following administration of study drug

Population: Modified intent-to-treat population of all randomized subjects analyzed by actual treatment received

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

Outcome measures

Outcome measures
Measure	G-Pen n=78 Participants A single 1 mg subcutaneous (SC) injection of G-Pen™ (glucagon injection)	Lilly Glucagon n=79 Participants A single 1 mg subcutaneous (SC) injection of Lilly Glucagon
Hypoglycemia Rescue: Intent-to-Treat Population	74 Participants	79 Participants

PRIMARY outcome

Timeframe: At 30 minutes following administration of study drug

Population: All randomized, treated subjects without a major protocol violation

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

Outcome measures

Outcome measures
Measure	G-Pen n=77 Participants A single 1 mg subcutaneous (SC) injection of G-Pen™ (glucagon injection)	Lilly Glucagon n=78 Participants A single 1 mg subcutaneous (SC) injection of Lilly Glucagon
Hypoglycemia Rescue: Per Protocol Population	74 Participants	78 Participants

PRIMARY outcome

Timeframe: At 30 minutes following administration of study drug

Population: Modified intent-to-treat population of all randomized subjects analyzed by actual treatment received

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

Outcome measures

Outcome measures
Measure	G-Pen n=78 Participants A single 1 mg subcutaneous (SC) injection of G-Pen™ (glucagon injection)	Lilly Glucagon n=79 Participants A single 1 mg subcutaneous (SC) injection of Lilly Glucagon
Hypoglycemia Rescue: Alternate Glucose Response Definition	76 Participants	79 Participants

SECONDARY outcome

Timeframe: At -5, 0, 10, 20, 30, 45, 60, and 90 minutes following administration of glucagon

Population: Modified intent-to-treat population of all randomized subjects analyzed by actual treatment received

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

Outcome measures

Outcome measures
Measure	G-Pen n=78 Participants A single 1 mg subcutaneous (SC) injection of G-Pen™ (glucagon injection)	Lilly Glucagon n=79 Participants A single 1 mg subcutaneous (SC) injection of Lilly Glucagon
Plasma Glucose Area Under the Curve (AUC)	11651.4 mg*min/dL Standard Deviation 2406.9	12260.4 mg*min/dL Standard Deviation 2134.2

SECONDARY outcome

Timeframe: At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon

Population: Modified intent-to-treat population of all randomized subjects analyzed by actual treatment received

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

Outcome measures

Outcome measures
Measure	G-Pen n=78 Participants A single 1 mg subcutaneous (SC) injection of G-Pen™ (glucagon injection)	Lilly Glucagon n=79 Participants A single 1 mg subcutaneous (SC) injection of Lilly Glucagon
Plasma Glucose Maximum Concentration (Cmax)	202.7 mg/dL Standard Deviation 41.8	193.5 mg/dL Standard Deviation 42.2

SECONDARY outcome

Timeframe: At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon

Population: Modified intent-to-treat population of all randomized subjects analyzed by actual treatment received

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

Outcome measures

Outcome measures
Measure	G-Pen n=78 Participants A single 1 mg subcutaneous (SC) injection of G-Pen™ (glucagon injection)	Lilly Glucagon n=79 Participants A single 1 mg subcutaneous (SC) injection of Lilly Glucagon
Plasma Glucose Time to Maximum Concentration (Tmax)	111.3 minutes Standard Deviation 33.5	100.4 minutes Standard Deviation 42.7

SECONDARY outcome

Timeframe: At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon

Population: Modified intent-to-treat population of all randomized subjects analyzed by actual treatment received

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

Outcome measures

Outcome measures
Measure	G-Pen n=78 Participants A single 1 mg subcutaneous (SC) injection of G-Pen™ (glucagon injection)	Lilly Glucagon n=79 Participants A single 1 mg subcutaneous (SC) injection of Lilly Glucagon
Plasma Glucose Time to Concentration > 70 mg/dL	19.9 minutes Standard Deviation 8.5	14.2 minutes Standard Deviation 4.3

SECONDARY outcome

Timeframe: 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

Population: Modified intent-to-treat population of all randomized subjects analyzed by actual treatment received

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

Outcome measures

Outcome measures
Measure	G-Pen n=77 Participants A single 1 mg subcutaneous (SC) injection of G-Pen™ (glucagon injection)	Lilly Glucagon n=79 Participants A single 1 mg subcutaneous (SC) injection of Lilly Glucagon
Time to Resolution of Hypoglycemia Symptoms Autonomic Symptoms	16.0 minutes Standard Deviation 11.5	14.2 minutes Standard Deviation 9.4
Time to Resolution of Hypoglycemia Symptoms Neuroglycopenic Symptoms	16.7 minutes Standard Deviation 10.2	14.3 minutes Standard Deviation 9.0
Time to Resolution of Hypoglycemia Symptoms All Symptoms	19.8 minutes Standard Deviation 11.7	17.0 minutes Standard Deviation 8.9

SECONDARY outcome

Timeframe: 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

Population: Modified intent-to-treat population of all randomized subjects analyzed by actual treatment received

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

Outcome measures

Outcome measures
Measure	G-Pen n=76 Participants A single 1 mg subcutaneous (SC) injection of G-Pen™ (glucagon injection)	Lilly Glucagon n=79 Participants A single 1 mg subcutaneous (SC) injection of Lilly Glucagon
Global Assessment of Hypoglycemia	16.8 minutes Standard Deviation 10.7	15.7 minutes Standard Deviation 8.3

POST_HOC outcome

Timeframe: At 30 minutes following administration of study drug

Population: Modified intent-to-treat population of all randomized subjects analyzed by actual treatment received

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

Outcome measures

Outcome measures
Measure	G-Pen n=78 Participants A single 1 mg subcutaneous (SC) injection of G-Pen™ (glucagon injection)	Lilly Glucagon n=79 Participants A single 1 mg subcutaneous (SC) injection of Lilly Glucagon
Hypoglycemia Rescue: Glucose or Symptomatic Response Definition	78 Participants	79 Participants

Adverse Events

G-Pen

Serious events: 0 serious events

Other events: 24 other events

Deaths: 0 deaths

Lilly Glucagon

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	G-Pen n=78 participants at risk A single 1 mg subcutaneous (SC) injection of G-Pen™ (glucagon injection)	Lilly Glucagon n=79 participants at risk A single 1 mg subcutaneous (SC) injection of Lilly Glucagon
Endocrine disorders hyperinsulinemic hypoglycemia	0.00% 0/78 • 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.	1.3% 1/79 • Number of events 1 • 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.

Other adverse events

Other adverse events
Measure	G-Pen n=78 participants at risk A single 1 mg subcutaneous (SC) injection of G-Pen™ (glucagon injection)	Lilly Glucagon n=79 participants at risk A single 1 mg subcutaneous (SC) injection of Lilly Glucagon
Gastrointestinal disorders Nausea	21.8% 17/78 • Number of events 18 • 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.	12.7% 10/79 • Number of events 10 • 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.
Gastrointestinal disorders Vomiting	6.4% 5/78 • Number of events 5 • 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.	5.1% 4/79 • Number of events 4 • 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.
Nervous system disorders Headache	2.6% 2/78 • Number of events 2 • 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.	2.5% 2/79 • Number of events 2 • 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.

Additional Information

Martin J. Cummins, VP, Clinical Development

Xeris Pharamaceuticals, Inc.

Phone: 806-282-2120

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place