Trial Outcomes & Findings for Equivalence of A Stable Liquid Glucagon Formulation With Freshly Reconstituted Lyophilized Glucagon (NCT NCT02018627)

Results Overview

tmax for Xeris vs. Lilly (non-inferiority)

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

20 participants

Primary outcome timeframe

every 2 minutes for 1 hour post-dose of each glucagon

Results posted on

2019-10-08

Participant Flow

20 subjects were enrolled in this study. One was ineligible after enrollment. 4 were enrolled and eligible, but were not able to schedule their study visit. 2 participated in "test run" experiments as we adjusted glucagon doses to account for concentration differences. 13 subjects completed experiments using the same protocol.

Participant milestones

Participant milestones
Measure	Xeris Glucagon First, Then Lilly Glucagon Xeris glucagon 50 micrograms, subcutaneous injection then Lilly glucagon 30 micrograms, subcutaneous injection Lilly glucagon: The subject is given an injection of lilly glucagon Xeris glucagon: The subject is given an injection of xeris glucagon	Lilly Glucagon First, Then Xeris Glucagon Lilly glucagon 30 micrograms, subcutaneous injection then Xeris glucagon 50 micrograms, subcutaneous injection Lilly glucagon: The subject is given an injection of lilly glucagon Xeris glucagon: The subject is given an injection of xeris glucagon
Overall Study STARTED	7	6
Overall Study COMPLETED	7	6
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Equivalence of A Stable Liquid Glucagon Formulation With Freshly Reconstituted Lyophilized Glucagon

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Xeris Glucagon First, Then Lilly Glucagon n=7 Participants Xeris glucagon 50 micrograms, subcutaneous injection, then Lilly glucagon 30 micrograms, subcutaneous injection Xeris glucagon: The subject is given an injection of xeris glucagon Lilly glucagon: The subject is given an injection of lilly glucagon	Lilly Glucagon First, Then Xeris Glucagon n=6 Participants Lilly glucagon 30 micrograms, subcutaneous injection, then Xeris glucagon 50 micrograms, subcutaneous injection Lilly glucagon: The subject is given an injection of lilly glucagon Xeris glucagon: The subject is given an injection of xeris glucagon	Total n=13 Participants Total of all reporting groups
Age, Continuous	57.0 years STANDARD_DEVIATION 11.8 • n=93 Participants	45.6 years STANDARD_DEVIATION 11.9 • n=4 Participants	51.7 years STANDARD_DEVIATION 12.8 • n=27 Participants
Sex: Female, Male Female	2 Participants n=93 Participants	3 Participants n=4 Participants	5 Participants n=27 Participants
Sex: Female, Male Male	5 Participants n=93 Participants	3 Participants n=4 Participants	8 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=93 Participants	6 Participants n=4 Participants	12 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Hemoglobin A1c	7.4 percent STANDARD_DEVIATION 1.3 • n=93 Participants	7.0 percent STANDARD_DEVIATION 0.6 • n=4 Participants	7.2 percent STANDARD_DEVIATION 1.0 • n=27 Participants

PRIMARY outcome

Timeframe: every 2 minutes for 1 hour post-dose of each glucagon

Population: 13 subjects completed the study following a consistent protocol using the glucagon doses described in the arm/group description. 7 subjects were randomized to get Xeris glucagon first, 6 subjects were randomized to get Lilly glucagon first. All 13 subjects received both glucagon injections, and the data is reported for each drug.

tmax for Xeris vs. Lilly (non-inferiority)

Outcome measures

Outcome measures
Measure	Xeris Glucagon n=13 Participants Xeris glucagon 50 micrograms, subcutaneous injection Xeris glucagon: The subject is given an injection of xeris glucagon	Lilly Glucagon n=13 Participants Lilly glucagon 30 micrograms, subcutaneous injection Lilly glucagon: The subject is given an injection of lilly glucagon
Tmax	23.8 minutes Standard Deviation 9.3	15.7 minutes Standard Deviation 3.0

SECONDARY outcome

Timeframe: every 2 minutes for 1 hour post-dose of each glucagon

Population: 13 subjects completed the study following a consistent protocol using the glucagon doses described in the arm/group description. 7 subjects were randomized to get Xeris glucagon first, 6 subjects were randomized to get Lilly glucagon first. All 13 subjects received both glucagon injections, and the data is reported for each drug.

Area over the curve for glucose infusion rate in the hour following administration (AOCGIR) for Xeris vs. Lilly (non-inferiority)

Outcome measures

Outcome measures
Measure	Xeris Glucagon n=13 Participants Xeris glucagon 50 micrograms, subcutaneous injection Xeris glucagon: The subject is given an injection of xeris glucagon	Lilly Glucagon n=13 Participants Lilly glucagon 30 micrograms, subcutaneous injection Lilly glucagon: The subject is given an injection of lilly glucagon
AOCGIR	201.1 mg*min/kg Standard Deviation 275.5	132.2 mg*min/kg Standard Deviation 87.9

SECONDARY outcome

Timeframe: every 2 minutes for 1 hour post-dose of each glucagon

Population: 13 subjects completed the study following a consistent protocol using the glucagon doses described in the arm/group description. 7 subjects were randomized to get Xeris glucagon first, 6 subjects were randomized to get Lilly glucagon first. All 13 subjects received both glucagon injections, and the data is reported for each drug.

Minimal glucose infusion rate (GIRmin) for Xeris vs. Lilly (non-inferiority)

Outcome measures

Outcome measures
Measure	Xeris Glucagon n=13 Participants Xeris glucagon 50 micrograms, subcutaneous injection Xeris glucagon: The subject is given an injection of xeris glucagon	Lilly Glucagon n=13 Participants Lilly glucagon 30 micrograms, subcutaneous injection Lilly glucagon: The subject is given an injection of lilly glucagon
GIRmin	2.9 dextrose mg/kg/min Standard Deviation 2.2	2.9 dextrose mg/kg/min Standard Deviation 1.8

SECONDARY outcome

Timeframe: every 2 minutes for 1 hour post-dose of each glucagon

Population: 13 subjects completed the study following a consistent protocol using the glucagon doses described in the arm/group description. 7 subjects were randomized to get Xeris glucagon first, 6 subjects were randomized to get Lilly glucagon first. All 13 subjects received both glucagon injections, and the data is reported for each drug.

Glucagon t½max for Xeris vs. Lilly (non-inferiority)

Outcome measures

Outcome measures
Measure	Xeris Glucagon n=13 Participants Xeris glucagon 50 micrograms, subcutaneous injection Xeris glucagon: The subject is given an injection of xeris glucagon	Lilly Glucagon n=13 Participants Lilly glucagon 30 micrograms, subcutaneous injection Lilly glucagon: The subject is given an injection of lilly glucagon
t½Max	11.3 minutes Standard Deviation 3.1	5.9 minutes Standard Deviation 2.1

SECONDARY outcome

Timeframe: immediately after injection

Population: 13 subjects completed the study following a consistent protocol using the glucagon doses described in the arm/group description. 7 subjects were randomized to get Xeris glucagon first, 6 subjects were randomized to get Lilly glucagon first. All 13 subjects received both glucagon injections, and the data is reported for each drug.

Quantitation of adverse events related to glucagon injection for Xeris vs. Lilly: -average Injection pain on a 10 cm standard VAS: 0 = no pain, 10 = worst imaginable pain reported immediately after injection of glucagon

Outcome measures

Outcome measures
Measure	Xeris Glucagon n=13 Participants Xeris glucagon 50 micrograms, subcutaneous injection Xeris glucagon: The subject is given an injection of xeris glucagon	Lilly Glucagon n=13 Participants Lilly glucagon 30 micrograms, subcutaneous injection Lilly glucagon: The subject is given an injection of lilly glucagon
Injection Pain	13.8 cm Standard Deviation 17.7	7.6 cm Standard Deviation 8.7

SECONDARY outcome

Timeframe: within 1 hour of injection

Population: 13 subjects completed the study following a consistent protocol using the glucagon doses described in the arm/group description. 7 subjects were randomized to get Xeris glucagon first, 6 subjects were randomized to get Lilly glucagon first. All 13 subjects received both glucagon injections, and the data is reported for each drug.

Quantitation of adverse events related to glucagon injection for Xeris vs. Lilly: -Injection site erythema or other local reaction, maximum diameter within 1 hour of injection

Outcome measures

Outcome measures
Measure	Xeris Glucagon n=13 Participants Xeris glucagon 50 micrograms, subcutaneous injection Xeris glucagon: The subject is given an injection of xeris glucagon	Lilly Glucagon n=13 Participants Lilly glucagon 30 micrograms, subcutaneous injection Lilly glucagon: The subject is given an injection of lilly glucagon
Injection Site Erythema	0 cm Standard Deviation 0	0 cm Standard Deviation 0

SECONDARY outcome

Timeframe: within 1 hour of injection

Population: 13 subjects completed the study following a consistent protocol using the glucagon doses described in the arm/group description. 7 subjects were randomized to get Xeris glucagon first, 6 subjects were randomized to get Lilly glucagon first. All 13 subjects received both glucagon injections, and the data is reported for each drug.

Quantitation of adverse events related to glucagon injection for Xeris vs. Lilly: -Maximal nausea within 1 hour of injection on a 10 cm VAS: no nausea = 0, vomiting = 10

Outcome measures

Outcome measures
Measure	Xeris Glucagon n=13 Participants Xeris glucagon 50 micrograms, subcutaneous injection Xeris glucagon: The subject is given an injection of xeris glucagon	Lilly Glucagon n=13 Participants Lilly glucagon 30 micrograms, subcutaneous injection Lilly glucagon: The subject is given an injection of lilly glucagon
Maximal Nausea	1.0 cm	2.3 cm

SECONDARY outcome

Timeframe: within 1 hour of injection

Population: 13 subjects completed the study following a consistent protocol using the glucagon doses described in the arm/group description. 7 subjects were randomized to get Xeris glucagon first, 6 subjects were randomized to get Lilly glucagon first. All 13 subjects received both glucagon injections, and the data is reported for each drug.

Average grade on the erythema and eschar formation portion of the Draize scale for dermal response (0 being the lowest, 4 being the highest)

Outcome measures

Outcome measures
Measure	Xeris Glucagon n=13 Participants Xeris glucagon 50 micrograms, subcutaneous injection Xeris glucagon: The subject is given an injection of xeris glucagon	Lilly Glucagon n=13 Participants Lilly glucagon 30 micrograms, subcutaneous injection Lilly glucagon: The subject is given an injection of lilly glucagon
Dermal Response (Draize Scale for Erythema and Eschar Formation)	0 score on draize scale Standard Deviation 0	0 score on draize scale Standard Deviation 0

SECONDARY outcome

Timeframe: within 1 hour of injection

Population: 13 subjects completed the study following a consistent protocol using the glucagon doses described in the arm/group description. 7 subjects were randomized to get Xeris glucagon first, 6 subjects were randomized to get Lilly glucagon first. All 13 subjects received both glucagon injections, and the data is reported for each drug.

Average grade on the edema formation portion of the Draize scale for dermal response (0 being the lowest, 4 being the highest)

Outcome measures

Outcome measures
Measure	Xeris Glucagon n=13 Participants Xeris glucagon 50 micrograms, subcutaneous injection Xeris glucagon: The subject is given an injection of xeris glucagon	Lilly Glucagon n=13 Participants Lilly glucagon 30 micrograms, subcutaneous injection Lilly glucagon: The subject is given an injection of lilly glucagon
Dermal Response (Draize Scale Grade for Edema Formation)	0 score on draize scale Standard Deviation 0	0 score on draize scale Standard Deviation 0

Adverse Events

Xeris Glucagon

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Lilly Glucagon

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Courtney Balliro, BS, RN, CDE

Massachusetts General Hospital

Phone: 617-726-1242

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place