Glucose Response of G-Pen (Glucagon Injection) in Pediatric T1D Patients

• Sponsor: Xeris Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03091673
• Collaborator: The Emmes Company, LLC (Industry)
• Enrollment: 31
• Locations: 7
• Arms: 2
• Actual Duration (Months): 6
• Patients Per Site: 4.4
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This is a sequential efficacy and safety study in pediatric patients with type 1 diabetes. Subjects will be administered insulin to induce a low normal glycemic state and will then receive an age-appropriate dose of G-Pen (glucagon injection) in a clinical research center (CRC) or comparable setting.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1	Drug: Glucagon	Phase 3

Detailed Description

This is an open-label, Phase 3 sequential efficacy and safety study in pediatric patients ages 2-17 with type 1 diabetes. Patients will complete the screening procedures up to 30 days before dosing to determine eligibility before enrollment to the treatment phase.

The procedure to evaluate the efficacy of G-Pen (glucagon injection) consists of inducing a low normal glycemic state by administration of insulin. Subjects ages 2-11 will then be given a 0.5 mg dose of G-Pen, while subjects ages 12-17 will receive a 1 mg dose of G-Pen. Subjects ages 12-17 will return for a second visit 1-4 weeks later and will receive a 0.5 mg dose of G-Pen when in a low normal glycemic stare. Plasma glucose and glucagon levels will be monitored for 90 and 180 minutes post-dosing, respectively, at all visits.

A follow-up phone call as a safety check will be conducted 3 - 14 days following administration of the final dose.

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Study to Evaluate the Glucose Response of G-Pen (Glucagon Injection) in Pediatric Patients With Type 1 Diabetes
• Actual Study Start Date: Mar 27, 2017
• Actual Primary Completion Date: Sep 7, 2017
• Actual Study Completion Date: Sep 27, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: G-Pen (glucagon injection) 0.5 mg A single 0.5 mg subcutaneous (SC) injection of G-Pen (glucagon injection)	Drug: Glucagon; 0.5 or 1.0 mg of pre-mixed liquid Xeris glucagon delivered via auto-injector; Other Names: G-Pen (glucagon injection)
Experimental: G-Pen (glucagon injection) 1.0 mg A single 1.0 mg subcutaneous (SC) injection of G-Pen (glucagon injection)	Drug: Glucagon; 0.5 or 1.0 mg of pre-mixed liquid Xeris glucagon delivered via auto-injector; Other Names: G-Pen (glucagon injection)

Outcome Measures

Primary Outcome Measures

1. Change in Plasma Glucose [0-30 minutes]

   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.

Secondary Outcome Measures

1. Time for Plasma Glucose to Increase by ≥25 mg/dL [0-90 minutes]

   Time for plasma glucose to increase by ≥25 mg/dL from baseline will be analyzed descriptively for each age cohort.

2. Plasma Glucagon Area Under the Curve [0-90 minutes]

   Plasma glucagon area under the curve (AUC) for each age cohort will be analyzed descriptively.

3. Plasma Glucagon Cmax [0-180 minutes]

   Plasma glucagon maximum concentration for each age cohort will be analyzed descriptively.

4. Plasma Glucagon Tmax [0-180 minutes]

   Plasma glucagon time to maximum concentration for each age cohort will be analyzed descriptively.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

• hematocrit less than or equal to 30%

• use of > 2.0 U/kg total insulin dose per day

• inadequate venous access

• current seizure disorder

• history of pheochromocytoma or disorder with increased risk of pheochromocytoma

• history of insulinoma

• history of glycogen storage disease.

• active use of alcohol or drugs of abuse

• administration of glucagon within 14 days of the first treatment visit

• participation in other studies involving an investigational drug or device within 30 days

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University	Stanford	California	United States	94305
2	Barbara Davis Center for Childhood Diabetes	Aurora	Colorado	United States	80045
3	Yale University	New Haven	Connecticut	United States	06511
4	University of Florida	Gainesville	Florida	United States	32611
5	Indiana University	Indianapolis	Indiana	United States	46202
6	University of Iowa	Iowa City	Iowa	United States	52422
7	Women & Children's Hospital of Buffalo	Buffalo	New York	United States	14222

Sponsors and Collaborators

• Xeris Pharmaceuticals
• The Emmes Company, LLC

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Dec 6, 2016
• Statistical Analysis Plan - Aug 16, 2017

More Information

Publications

None provided.

• Responsible Party: Xeris Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03091673
• Other Study ID Numbers: XSGP-302
• First Posted: Mar 27, 2017
• Last Update Posted: Dec 11, 2018
• Last Verified: Nov 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Diabetes Mellitus, Type 1; Glucagon; Glucagon-Like Peptide 1

Study Results

Participant Flow

Arm/Group Title	G-Pen (Glucagon Injection) 0.5 mg	G-Pen (Glucagon Injection) 1.0 mg
Arm/Group Description	A single 0.5 mg subcutaneous (SC) injection of G-Pen (glucagon injection) Glucagon: 0.5 or 1.0 mg of pre-mixed liquid Xeris glucagon delivered via auto-injector	A single 1.0 mg subcutaneous (SC) injection of G-Pen (glucagon injection) Glucagon: 0.5 or 1.0 mg of pre-mixed liquid Xeris glucagon delivered via auto-injector
Period Title: First Dose
STARTED	31	0
COMPLETED	31	0
NOT COMPLETED	0	0
Period Title: First Dose
STARTED	0	11
COMPLETED	0	11
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Subjects 2 to <6 Years of Age	Subjects 6 to <12 Years of Age	Subjects 12 to <18 Years of Age	Total
Arm/Group Description	Study subjects at least 2, but less than 6 years of age at the time of dosing	Study subjects at least 6, but less than 12 years of age at the time of dosing	Study subjects at least 12, but less than 18 years of age at the time of dosing	Total of all reporting groups
Overall Participants	7	13	11	31
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	4.96 (1.1)	9.95 (2.25)	15.48 (1.58)	10.79 (4.41)
Sex: Female, Male (Count of Participants)
Female	5 71.4%	5 38.5%	6 54.5%	16 51.6%
Male	2 28.6%	8 61.5%	5 45.5%	15 48.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	7 100%	13 100%	11 100%	31 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	2 28.6%	1 7.7%	0 0%	3 9.7%
White	5 71.4%	12 92.3%	11 100%	28 90.3%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	7 100%	13 100%	11 100%	31 100%

Outcome Measures

1. Primary Outcome

Title	Change in Plasma Glucose
Description	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.
Time Frame	0-30 minutes

Outcome Measure Data

Analysis Population Description

All enrolled subjects.

Arm/Group Title	Subjects 2 to <6 Years of Age	Subjects 6 to <12 Years of Age	Subjects 12 to <18 Years of Age
Arm/Group Description	Study subjects at least 2, but less than 6 years of age at the time of receiving a 0.5 mg dose of G-Pen.	Study subjects at least 6, but less than 12 years of age at the time of receiving a 0.5 mg dose of G-Pen.	Study subjects at least 12, but less than 18 years of age at the time of receiving a 1 mg dose of G-Pen.
Measure Participants	7	13	11
Mean (Standard Deviation) [mg/dL]	81.4 (18.3)	84.2 (25.3)	54.0 (27.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Subjects 2 to <6 Years of Age, Subjects 6 to <12 Years of Age, Subjects 12 to <18 Years of Age
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value was computed using a t-test to determine if change in plasma glucose from baseline to 30 minutes was zero.
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Time for Plasma Glucose to Increase by ≥25 mg/dL
Description	Time for plasma glucose to increase by ≥25 mg/dL from baseline will be analyzed descriptively for each age cohort.
Time Frame	0-90 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subjects 2 to <6 Years of Age	Subjects 6 to <12 Years of Age	Subjects 12 to <18 Years of Age
Arm/Group Description	Study subjects at least 2, but less than 6 years of age at the time of receiving a 0.5 mg dose of G-Pen.	Study subjects at least 6, but less than 12 years of age at the time of receiving a 0.5 mg dose of G-Pen.	Study subjects at least 12, but less than 18 years of age at the time of receiving a 1 mg dose of G-Pen.
Measure Participants	7	13	11
Mean (Standard Deviation) [minutes]	16.4 (3.78)	16.2 (4.63)	26.6 (9.51)

3. Secondary Outcome

Title	Plasma Glucagon Area Under the Curve
Description	Plasma glucagon area under the curve (AUC) for each age cohort will be analyzed descriptively.
Time Frame	0-90 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subjects 2 to <6 Years of Age	Subjects 6 to <12 Years of Age	Subjects 12 to <18 Years of Age
Arm/Group Description	Study subjects at least 2, but less than 6 years of age at the time of receiving a 0.5 mg dose of G-Pen	Study subjects at least 6, but less than 12 years of age at the time of receiving a 0.5 mg dose of G-Pen	Study subjects at least 12, but less than 18 years of age at the time of receiving a 1 mg dose of G-Pen
Measure Participants	7	13	11
Mean (Standard Deviation) [min*mg/dL]	14440.8 (2114.9)	14392.3 (2698.4)	13105.5 (13105.45)

4. Secondary Outcome

Title	Plasma Glucagon Cmax
Description	Plasma glucagon maximum concentration for each age cohort will be analyzed descriptively.
Time Frame	0-180 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subjects 2 to <6 Years of Age	Subjects 6 to <12 Years of Age	Subjects 12 to <18 Years of Age
Arm/Group Description	Study subjects at least 2, but less than 6 years of age at the time of receiving a 0.5 mg dose of G-Pen.	Study subjects at least 6, but less than 12 years of age at the time of receiving a 0.5 mg dose of G-Pen.	Study subjects at least 12, but less than 18 years of age at the time of receiving a 1 mg dose of G-Pen.
Measure Participants	7	13	11
Mean (Standard Deviation) [mg/dL]	202.3 (35.9)	216.3 (51.2)	199.0 (57.0)

5. Secondary Outcome

Title	Plasma Glucagon Tmax
Description	Plasma glucagon time to maximum concentration for each age cohort will be analyzed descriptively.
Time Frame	0-180 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subjects 2 to <6 Years of Age	Subjects 6 to <12 Years of Age	Subjects 12 to <18 Years of Age
Arm/Group Description	Study subjects at least 2, but less than 6 years of age at the time of receiving a 0.5 mg dose of G-Pen.	Study subjects at least 6, but less than 12 years of age at the time of receiving a 0.5 mg dose of G-Pen.	Study subjects at least 12, but less than 18 years of age at the time of receiving a 1 mg dose of G-Pen.
Measure Participants	7	13	11
Mean (Standard Deviation) [minutes]	66.6 (10.5)	68.5 (15.3)	81.2 (14.9)

Adverse Events

Time Frame	Adverse events were collected from the signing of informed consent through the follow-up phone call, which was completed 3-14 days after the last dose of treatment. The maximum adverse event (AE) collection period was 44 days for subjects receiving a single dose, and 72 days for subjects receiving 2 doses of G-Pen.
Arm/Group Title	Subjects 2 to <6 Years of Age		Subjects 6 to <12 Years of Age		Subjects 12 to <18 Years of Age
Arm/Group Description	Study subjects at least 2, but less than 6 years of age at the time of receiving a 0.5 mg dose of G-Pen.		Study subjects at least 6, but less than 12 years of age at the time of receiving a 0.5 mg dose of G-Pen.		Study subjects at least 12, but less than 18 years of age at the time of receiving a 1 mg dose of G-Pen.
All Cause Mortality
	Subjects 2 to <6 Years of Age		Subjects 6 to <12 Years of Age		Subjects 12 to <18 Years of Age
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/13 (0%)		0/11 (0%)
Serious Adverse Events
	Subjects 2 to <6 Years of Age		Subjects 6 to <12 Years of Age		Subjects 12 to <18 Years of Age
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/13 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	Subjects 2 to <6 Years of Age		Subjects 6 to <12 Years of Age		Subjects 12 to <18 Years of Age
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/7 (71.4%)		12/13 (92.3%)		8/11 (72.7%)
Gastrointestinal disorders
Nausea	3/7 (42.9%)	4	7/13 (53.8%)	7	4/11 (36.4%)	4
Vomiting	1/7 (14.3%)	1	3/13 (23.1%)	3	2/11 (18.2%)	2
Metabolism and nutrition disorders
Hyperglycemia	1/7 (14.3%)	1	1/13 (7.7%)	1	0/11 (0%)	0
Hypoglycemia	2/7 (28.6%)	2	7/13 (53.8%)	7	3/11 (27.3%)	3
Nervous system disorders
Headache	0/7 (0%)	0	2/13 (15.4%)	2	0/11 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.