HypoglycemiaPhase 3NCT02656069

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

A Phase 3 study testing G-Pen (glucagon injection) and Lilly Glucagon (glucagon injection [rDNA origin]) in people with Hypoglycemia and Diabetes Mellitus, Type 1, run by Xeris Pharmaceuticals at 7 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is a blinded, randomized crossover study to compare the safety and efficacy of G-Pen (glucagon injection) to Lilly Glucagon (glucagon for injection [rDNA origin]) for hypoglycemia rescue of adult patients with type 1 diabetes. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Hypoglycemia, Diabetes Mellitus, Type 1
What is being tested?: G-Pen (glucagon injection) and Lilly Glucagon (glucagon injection [rDNA origin])
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 80 participants
Where: 7 sitesin 2 countries
Study dates: 15 Mar 2017to 25 Sep 2017
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

diagnosed with type 1 diabetes mellitus for at least 24 months
usage of daily insulin treatment
random serum C-peptide concentration < 0.5 ng/mL

Who cannot join

pregnant or nursing
HbA1c >9.0%
renal insufficiency
hepatic synthetic insufficiency
aspartate or alanine aminotransferase > 3 times the upper limit of normal
hematocrit less than or equal to 30%

Show all 22Show fewer

use of > 2.0 U/kg total insulin dose per day
inadequate bilateral venous access in both arms
congestive heart failure, New York Heart Association class II, III or IV
active malignancy within 5 years, except basal cell or squamous cell skin cancers
history of breast cancer or malignant melanoma
major surgical operation within 30 days
current seizure disorder.
current bleeding disorder, treatment with warfarin, or platelet count below 50,000
history of pheochromocytoma or disorder with increased risk of pheochromocytoma
history of insulinoma
history of glycogen storage disease.
positive for HIV, hepatitis C virus or active hepatitis B virus infection
whole blood donation of 1 pint (500 mL) within 8 weeks
active substance or alcohol abuse
administration of glucagon within 28 days
participation in other studies involving an investigational drug or device within 30 days

Trial locations and contacts

7 sites in 2 countries.

Country

City, postcode or hospital

7 sites in 2 countries

United States6 sites

University of Alabama at Birmingham
Birmingham, Alabama, 35294
ProSciento, Inc.
Chula Vista, California, 91911
AMCR Institute
Escondido, California, 92025
Rainier Research
Renton, Washington, 98057
Clinical Trials of Texas, Inc.
San Antonio, Texas, 78229
Diablo Clinical Research
Walnut Creek, California, 94598

Other trials in United States

Canada1 site

LMC Diabetes & Endocrinology
Toronto, Ontario, M4G 3E8

Other trials in Canada

About this study

Official title: G-Pen (Glucagon Injection) Compared to Lilly Glucagon (Glucagon for Injection [RDNA Origin]) for Induced Hypoglycemia Rescue in Adult Patients With T1DM: A Phase 3, Multi-center, Randomized, Blinded, 2-Way Crossover Study to Evaluate Efficacy and Safety

Read the detailed description

This is a blinded, randomized, Phase 3 comparative efficacy and safety study in adults with type 1 diabetes. Patients will complete screening procedures up to 60 days before randomization to determine eligibility before enrollment to the treatment phase.

The procedure for evaluating the efficacy of the G-Pen (glucagon injection) consists of inducing hypoglycemia by intravenous administration of regular insulin diluted in normal saline. Each participant will undergo two episodes of insulin-induced hypoglycemia, and in random order will receive 1 mg G-Pen (glucagon injection) during one episode and 1 mg Lilly Glucagon during the other episode. There will be wash out period of 7-28 days between treatment visits.

Blood glucose levels will be monitored post-dosing, with a return of plasma glucose to a concentration > 70 mg/dL within 30 minutes signifying successful hypoglycemia rescue. As a confirmation of efficacy, subjects will complete a questionnaire concerning changes in symptoms of hypoglycemia following treatment with glucagon.

Subjects will return for a follow-up safety visit 3-14 days following administration of the final dose of glucagon.

Conditions: Hypoglycemia, Diabetes Mellitus, Type 1
Being tested: G-Pen (glucagon injection), Lilly Glucagon (glucagon injection [rDNA origin])
Medical subject headings: Hypoglycemia, Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

G-Pen (glucagon injection)Drug
Also called glucagon
1 mg of pre-mixed liquid Xeris glucagon delivered via auto-injector
Lilly Glucagon (glucagon injection [rDNA origin])Drug
Also called glucagon
1 mg of Lilly glucagon reconstituted from lyophilized powder

Study groups in NCT02656069
Study group	Role	What they receive
G-Pen first, then Lilly Glucagon	Other	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]) Receives: Drug: G-Pen (glucagon injection); Drug: Lilly Glucagon (glucagon injection [rDNA origin])
Lilly Glucagon first, then G-Pen	Other	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) Receives: Drug: G-Pen (glucagon injection); Drug: Lilly Glucagon (glucagon injection [rDNA origin])

What is being measured

The primary outcome is the main question the study is designed to answer.

Hypoglycemia Rescue: Intent-to-Treat Population
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
Measured: At 30 minutes following administration of study drug
Hypoglycemia Rescue: Per Protocol Population
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
Measured: At 30 minutes following administration of study drug
Hypoglycemia Rescue: Alternate Glucose Response Definition
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
Measured: At 30 minutes following administration of study drug

Secondary outcomes (6)

Plasma Glucose Area Under the Curve (AUC)
Pharmacodynamic endpoint of plasma glucose AUC from baseline to 90 minutes following administration of glucagon
Measured: At -5, 0, 10, 20, 30, 45, 60, and 90 minutes following administration of glucagon
Plasma Glucose Maximum Concentration (Cmax)
Pharmacodynamic endpoint of plasma glucose Cmax from baseline to 4 hours following administration of glucagon
Measured: At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon
Plasma Glucose Time to Maximum Concentration (Tmax)
Pharmacodynamic endpoint of plasma glucose Tmax from baseline to 4 hours following administration of glucagon
Measured: At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon
Plasma Glucose Time to Concentration > 70 mg/dL
Pharmacodynamic endpoint of time to achieve a plasma glucose concentration > 70 mg/dL following administration of glucagon
Measured: At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon
Time to Resolution of Hypoglycemia Symptoms
Time to resolution of mean autonomic, mean neuroglycopenic and mean total hypoglycemia symptom scores from baseline through 90 minutes following administration of glucagon.
Measured: 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
Global Assessment of Hypoglycemia
Time to resolution of the overall sensation of hypoglycemia following administration of glucagon
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 Mar 201725 Sep 2017

First posted14 Jan 2016 (estimated)
Study start15 Mar 2017
Primary completion14 Aug 2017
Study completion25 Sep 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HypoglycemiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 80 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02656069
Sponsor's protocol ID: XSGP-301
Status last verified: Sep 2018
First submitted: 12 Jan 2016
Last updated: 30 Oct 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 34620618

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 30 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: G-Pen (Glucagon Injection) Compared to Lilly Glucagon (Glucagon for Injection [RDNA Origin]) for Induced Hypoglycemia Rescue in Adult Patients With T1DM: A Phase 3, Multi-center, Randomized, Blinded, 2-Way Crossover Study to Evaluate Efficacy and Safety
ClinicalTrials.gov ID: NCT02656069
Acronym / sponsor ID: XSGP-301
Conditions: Hypoglycemia, Diabetes Mellitus, Type 1
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 80 participants (actual)
Lead sponsor: Xeris PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 15 Mar 2017 (actual)
Primary completion: 14 Aug 2017 (actual)
Study completion: 25 Sep 2017 (actual)
First posted: 14 Jan 2016 (estimated)
Results: Posted 28 Sep 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Subjects will return for a follow-up safety visit 3-14 days following administration of the final dose of glucagon.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
G-Pen first, then Lilly Glucagon	Other	Drug: G-Pen (glucagon injection), Drug: Lilly Glucagon (glucagon injection [rDNA origin])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])
Lilly Glucagon first, then G-Pen	Other	Drug: G-Pen (glucagon injection), Drug: Lilly Glucagon (glucagon injection [rDNA origin])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)

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

diagnosed with type 1 diabetes mellitus for at least 24 months
usage of daily insulin treatment
random serum C-peptide concentration < 0.5 ng/mL

Key exclusion criteria (22 listed)

pregnant or nursing
HbA1c >9.0%
renal insufficiency
hepatic synthetic insufficiency
aspartate or alanine aminotransferase > 3 times the upper limit of normal

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
G-Pen (glucagon injection)Also: glucagon1 mg of pre-mixed liquid Xeris glucagon delivered via auto-injector	Drug	G-Pen first, then Lilly Glucagon, Lilly Glucagon first, then G-Pen
Lilly Glucagon (glucagon injection [rDNA origin])Also: glucagon1 mg of Lilly glucagon reconstituted from lyophilized powder	Drug	G-Pen first, then Lilly Glucagon, Lilly Glucagon first, then G-Pen

Primary outcome

Hypoglycemia Rescue: Intent-to-Treat Population
Time frame: At 30 minutes following administration of study drug
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
Hypoglycemia Rescue: Per Protocol Population
Time frame: At 30 minutes following administration of study drug
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
Hypoglycemia Rescue: Alternate Glucose Response Definition
Time frame: At 30 minutes following administration of study drug
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

6 secondary outcomes

Plasma Glucose Area Under the Curve (AUC)
Time frame: At -5, 0, 10, 20, 30, 45, 60, and 90 minutes following administration of glucagon
Plasma Glucose Maximum Concentration (Cmax)
Time frame: At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon
Plasma Glucose Time to Maximum Concentration (Tmax)
Time frame: At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon
Plasma Glucose Time to Concentration > 70 mg/dL
Time frame: At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon
Time to Resolution of Hypoglycemia Symptoms
Time frame: 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
Global Assessment of Hypoglycemia
Time frame: 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

Results and safety

Results posted to the registry on 28 Sep 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
G-Pen First, Then Lilly Glucagon	44	44
Lilly Glucagon First, Then G-Pen	36	36

Primary outcome: Hypoglycemia Rescue: Intent-to-Treat Population

Time frame: At 30 minutes following administration of study drug. Count of participants. Unit: Participants

Measure	G-Pen n = 78	Lilly Glucagon n = 79
Value	74	79

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

Primary outcome: Hypoglycemia Rescue: Per Protocol Population

Time frame: At 30 minutes following administration of study drug. Count of participants. Unit: Participants

Measure	G-Pen n = 77	Lilly Glucagon n = 78
Value	74	78

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

Primary outcome: Hypoglycemia Rescue: Alternate Glucose Response Definition

Time frame: At 30 minutes following administration of study drug. Count of participants. Unit: Participants

Measure	G-Pen n = 78	Lilly Glucagon n = 79
Value	76	79

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

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: 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 reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
G-Pen	0 of 78 (0%)	24 of 78 (30.8%)	0 of 78
Lilly Glucagon	1 of 79 (1.3%)	16 of 79 (20.3%)	0 of 79

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 34620618Christiansen 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

7 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Hypoglycemia Rescue: Intent-to-Treat Population (time frame: At 30 minutes following administration of study drug). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02656069, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2018.