Insulin HypoglycemiaPhase 3NCT03738865
G-Pen Compared to Glucagen Hypokit for Severe Hypoglycemia Rescue in Adults With Type 1 Diabetes
A Phase 3 study testing G-Pen and Novo Glucagon in people with Insulin Hypoglycemia and Type 1 Diabetes Mellitus, run by Xeris Pharmaceuticals at 7 sites in 3 countries.
Trial summary
This is a multi-center, randomized, controlled, single-blind, two-way crossover efficacy and safety study in subjects with Type 1 diabetes mellitus. The study involves two daytime clinical research center (CRC) visits with random assignment to receive G-Pen glucagon 1 mg during one period and Novo Glucagon 1 mg during… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Insulin Hypoglycemia, Type 1 Diabetes Mellitus, Severe Hypoglycemia
- What is being tested?
- G-Pen and Novo Glucagon
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 132 participants
- Where
- 7 sitesin 3 countries
- Study dates
- 27 Sep 2018to 2 Apr 2019
- 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
- Males and non-pregnant females diagnosed with type 1 diabetes (T1D) for at least 24 months.
- Current usage of daily insulin treatment that includes having an assigned "correction factor" for managing hyperglycemia.
- Age 18 to 75 years, inclusive.
- Random serum C-peptide concentration < 0.6 ng/mL.
- Willingness to follow all study procedures, including attending all clinic visits.
- Subject has provided informed consent as evidenced by a signed and dated informed consent form (ICF) completed before any trial-related activities occur.
Who cannot join
- Pregnancy
- Glycated hemoglobin (HbA1c) > 10% at Screening.
- Body mass index (BMI) > 40 kg/m2.
- Renal insufficiency (serum creatinine greater than 3.0 mg/dL) or end-stage renal disease requiring renal replacement therapy.
- Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) equal to or greater than 3 times the upper limit of normal.
- Hepatic synthetic insufficiency as defined as a serum albumin of less than 3.0 g/dL.
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- Hematocrit < 30%.
- Blood pressure (BP) readings at Screening where systolic blood pressure (SBP) < 90 or > 150 mm Hg, and diastolic blood pressure (DBP) < 50 or > 100 mm Hg.
- Clinically significant electrocardiogram (ECG) abnormalities.
- Use of total insulin dose per day > 2 U/kg.
- Inadequate venous access.
- Congestive heart failure, New York Heart Association (NYHA) class III or IV.
- History of myocardial infarction, unstable angina, or revascularization within the past 6 months.
- History of a cerebrovascular accident in the past 6 months or with major neurological deficits.
- Active malignancy within 5 years from Screening, except basal cell or squamous cell skin cancers. Any history of breast cancer or malignant melanoma will be exclusionary.
- Major surgical operation within 30 days prior to Screening.
- Current seizure disorder (other than with suspect or documented hypoglycemia).
- Current bleeding disorder, treatment with warfarin, or platelet count below 50 × 109 per liter.
- History of pheochromocytoma or disorder with increased risk of pheochromocytoma (multiple endocrine neoplasia type 2 (MEN 2), neurofibromatosis, or Von Hippel-Lindau disease).
- History of insulinoma.
- History of allergies to glucagon or glucagon-like products, or any history of significant hypersensitivity to glucagon or any related products or to any of the excipients (DMSO and trehalose) in the investigational formulation.
- History of glycogen storage disease.
- Subject tests positive for human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) infection (hepatitis B surface antigen positive [HBsAg+]) at Screening.
- Active substance other than tetrahydrocannabinol (THC) or alcohol abuse (more than 21 drinks per week for male subjects or 14 drinks per week for female subject).
- Administration of glucagon within 7 days of Screening.
- Participation in other studies involving administration of an investigational drug or device within 30 days or 5 half-lives, whichever is longer, before Screening for the current study and during participation in the current study.
- Any other reason the Investigator deems exclusionary.
Trial locations and contacts
7 sites in 3 countries.
7 sites in 3 countries
United States4 sites
Atlanta Diabetes Associates
Atlanta, Georgia, 30318
PPD-Las Vegas Clinical Research Unit
Las Vegas, Nevada, 89113
Rainier Research Center
Renton, Washington, 98057
Diablo Clinical Research
Walnut Creek, California, 94598
Canada2 sites
AltaSciences
Montreal, Quebec, H3P 3P1
LMC Diabetes & Endocrinology
Toronto, Ontario, M4G 3E8
Austria1 site
Medizinische Universität Graz-Center for Medical Research
Graz, 8010
About this study
Official title: G-Pen (Glucagon Injection) Compared to GlucaGen® Hypokit® (Glucagon) for Induced Hypoglycemia Rescue in Adults With T1D: A Phase 3 Multi-center, Randomized, Controlled, Single Blind, 2-way Crossover Study to Evaluate Efficacy and Safety
This is a multi-center, randomized, controlled, single-blind, two-way crossover efficacy and safety study in subjects with Type 1 diabetes mellitus. The study involves two daytime clinical research center (CRC) visits with random assignment to receive G-Pen glucagon 1 mg during one period and Novo Glucagon 1 mg during the other. Each daytime visit is preceded by an overnight stay in the CRC. In the morning of the inpatient study visit, the subject is brought into a state of severe hypoglycemia through IV administration of regular insulin diluted in normal saline. After a hypoglycemic state with plasma glucose < 54 mg/dL (3 mmol/L) is verified, the subject is administered a dose of G-Pen or Novo Glucagon via subcutaneous injection. Plasma glucose levels are monitored for up to 180 minutes post-dosing, with a value of >70.0 mg/dL (3.89 mmol/L) or an increase of > 20 mg/dL (>1.11 mmol/L) within 30 minutes of glucagon administration indicating a positive response. After 3 hours, the subject is given a meal and discharged when medically stable. After a wash-out period of 7 to 28 days, subjects return to the CRC, and the procedures are repeated with each subject crossed over to the other treatment. A follow-up visit as a safety check is conducted 2-7 days following administration of the final dose of study drug.
- Being tested
- G-Pen, Novo Glucagon
- Keywords
- glucagon, hypoglycemia
- Medical subject headings
- Diabetes Mellitus, Type 1, Hypoglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
G-PenDrug
Also called glucagon
1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector
Novo GlucagonDrug
Also called Glucagen Hypokit
1 mg subcutaneous injection of Novo Glucagon (glucagon injection)
| Study group | Role | What they receive |
|---|---|---|
| G-Pen followed by Novo Glucagon | Experimental | 1 mg G-Pen at the first treatment visit followed by 1 mg Novo Glucagon at the second treatment visit Receives: Drug: G-Pen; Drug: Novo Glucagon |
| Novo Glucagon followed by G-Pen | Active comparator | 1 mg Novo Glucagon at the first treatment visit followed by 1 mg G-Pen at the second treatment visit Receives: Drug: G-Pen; Drug: Novo Glucagon |
What is being measured
The primary outcome is the main question the study is designed to answer.
Severe Hypoglycemia Rescue
Number of subjects with an increase in plasma glucose concentration from below 54 mg/dL (3 mmol/L) to greater than 70 mg/dL (3.89 mmol/L) or an increase in plasma glucose concentration > 20 mg/dL (> 1.11 mmol/L) within 30 minutes after administration of glucagon
Measured: At 30 minutes following administration of study drug
Secondary outcomes (4)
Plasma Glucose Response 1
Number of subjects with an increase in plasma glucose concentration from below 54 mg/dL (3 mmol/L) to greater than 70 mg/dL (3.89 mmol/L) within 30 minutes of a decision to dose
Measured: At 30 minutes following a decision to administer study drug
Plasma Glucose Response 2
Number of subjects with an increase in plasma glucose concentration > 20 mg/dL (> 1.11 mmol/L) after administration of glucagon.
Measured: At 0-30 minutes following a decision to administer study drug
Administration Time
Mean time (minutes) to administer study drug from a decision to dose
Measured: At 0-10 minutes from a decision to administer study drug
Hypoglycemia Resolution
Mean time (minutes) to complete resolution of the overall sensation of hypoglycemia from a decision to dose
Measured: At 0-90 minutes following administration of study drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2018
- Study start27 Sep 2018
- Primary completion29 Mar 2019
- Study completion2 Apr 2019
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 Insulin 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
- Single blind
- Who is masked
- Participant
- Enrolment
- 132 participants (actual)
Sponsor and investigators
- Lead sponsor
- Xeris Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Empiristat, Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03738865
- Sponsor's protocol ID
- XSGP-304
- Status last verified
- May 2020
- First submitted
- 8 Nov 2018
- Last updated
- 22 May 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Pieber TR, Aronson R, Christiansen MP, Bode B, Junaidi K, Conoscenti V. Efficacy, safety, tolerability, and noninferiority phase 3 study of glucagon as a ready-to-use room temperature liquid stable formulation versus a lyophilised formulation for the biochemical recovery and symptomatic relief of insulin-induced severe hypoglycaemia in adults with type 1 diabetes. Diabetes Obes Metab. 2022 Jul;24(7):1394-1397. doi: 10.1111/dom.14699. Epub 2022 Apr 28. No abstract available.
PubMed 35322535
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- G-Pen (Glucagon Injection) Compared to GlucaGen® Hypokit® (Glucagon) for Induced Hypoglycemia Rescue in Adults With T1D: A Phase 3 Multi-center, Randomized, Controlled, Single Blind, 2-way Crossover Study to Evaluate Efficacy and Safety
- ClinicalTrials.gov ID
- NCT03738865
- Acronym / sponsor ID
- XSGP-304
- Keywords
- glucagon, hypoglycemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 132 participants (actual)
- Lead sponsor
- Xeris PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- Empiristat, Inc.
- Study start
- 27 Sep 2018 (actual)
- Primary completion
- 29 Mar 2019 (actual)
- Study completion
- 2 Apr 2019 (actual)
- First posted
- 13 Nov 2018 (actual)
- Results
- Posted 13 May 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multi-center, randomized, controlled, single-blind, two-way crossover efficacy and safety study in subjects with Type 1 diabetes mellitus. The study involves two daytime clinical research center (CRC) visits with random assignment to receive G-Pen glucagon 1 mg during one period and Novo Glucagon 1 mg during the other. Each daytime visit is preceded by an overnight stay in the CRC. In the morning of the inpatient study visit, the subject is brought into a state of severe hypoglycemia through IV administration of regular insulin diluted in normal saline. After a hypoglycemic state with plasma glucose < 54 mg/dL (3 mmol/L) is verified, the subject is administered a dose of G-Pen or Novo Glucagon via subcutaneous injection. Plasma glucose levels are monitored for up to 180 minutes post-dosing, with a value of >70.0 mg/dL (3.89 mmol/L) or an increase of > 20 mg/dL (>1.11 mmol/L) within 30 minutes of glucagon administration indicating a positive response. After 3 hours, the subject is given a meal and discharged when medically stable. After a wash-out period of 7 to 28 days, subjects return to the CRC, and the procedures are repeated with each subject crossed over to the other treatment. A follow-up visit as a safety check is conducted 2-7 days following administration of the final dose of study drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| G-Pen followed by Novo Glucagon | Experimental | Drug: G-Pen, Drug: Novo Glucagon1 mg G-Pen at the first treatment visit followed by 1 mg Novo Glucagon at the second treatment visit |
| Novo Glucagon followed by G-Pen | Active comparator | Drug: G-Pen, Drug: Novo Glucagon1 mg Novo Glucagon at the first treatment visit followed by 1 mg G-Pen at the second treatment visit |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Males and non-pregnant females diagnosed with type 1 diabetes (T1D) for at least 24 months.
- Current usage of daily insulin treatment that includes having an assigned "correction factor" for managing hyperglycemia.
- Age 18 to 75 years, inclusive.
- Random serum C-peptide concentration < 0.6 ng/mL.
- Willingness to follow all study procedures, including attending all clinic visits.
Key exclusion criteria (27 listed)
- Pregnancy
- Glycated hemoglobin (HbA1c) > 10% at Screening.
- Body mass index (BMI) > 40 kg/m2.
- Renal insufficiency (serum creatinine greater than 3.0 mg/dL) or end-stage renal disease requiring renal replacement therapy.
- Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) equal to or greater than 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-PenAlso: glucagon1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector | Drug | G-Pen followed by Novo Glucagon, Novo Glucagon followed by G-Pen |
| Novo GlucagonAlso: Glucagen Hypokit1 mg subcutaneous injection of Novo Glucagon (glucagon injection) | Drug | G-Pen followed by Novo Glucagon, Novo Glucagon followed by G-Pen |
Primary outcome
Severe Hypoglycemia Rescue
Time frame: At 30 minutes following administration of study drug
Number of subjects with an increase in plasma glucose concentration from below 54 mg/dL (3 mmol/L) to greater than 70 mg/dL (3.89 mmol/L) or an increase in plasma glucose concentration > 20 mg/dL (> 1.11 mmol/L) within 30 minutes after administration of glucagon
4 secondary outcomes
Plasma Glucose Response 1
Time frame: At 30 minutes following a decision to administer study drug
Plasma Glucose Response 2
Time frame: At 0-30 minutes following a decision to administer study drug
Administration Time
Time frame: At 0-10 minutes from a decision to administer study drug
Hypoglycemia Resolution
Time frame: At 0-90 minutes following administration of study drug
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35322535Pieber TR, Aronson R, Christiansen MP, Bode B, Junaidi K, Conoscenti V. Efficacy, safety, tolerability, and noninferiority phase 3 study of glucagon as a ready-to-use room temperature liquid stable formulation versus a lyophilised formulation for the biochemical recovery and symptomatic relief of insulin-induced severe hypoglycaemia in adults with type 1 diabetes. Diabetes Obes Metab. 2022 Jul;24(7):1394-1397. doi: 10.1111/dom.14699. Epub 2022 Apr 28. No abstract available.
- 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 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing G-Pen and Novo Glucagon in people with Insulin Hypoglycemia and Type 1 Diabetes Mellitus, run by Xeris Pharmaceuticals at 7 sites in 3 countries.
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 6 inclusion and 27 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 22 May 2020. 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, Austria. 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 13 May 2020). 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?
Severe Hypoglycemia Rescue (time frame: At 30 minutes following administration of study drug). 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 NCT03738865, 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 22 May 2020.