Insulin HypoglycemiaPhase 3NCT03439072
G-Pen™ Compared to Lilly Glucagon for Hypoglycemia Rescue in Adults With Type 1 Diabetes
A Phase 3 study testing G-Pen and Lilly Glucagon in people with Insulin Hypoglycemia and Type 1 Diabetes Mellitus, run by Xeris Pharmaceuticals at 6 sites in 2 countries.
Trial summary
This is a non-inferiority, 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 Lilly… 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 Lilly Glucagon
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 81 participants
- Where
- 6 sitesin 2 countries
- Study dates
- 23 Jan 2018to 3 May 2018
- 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 females diagnosed with type 1 diabetes mellitus for at least 24 months.
- Current usage of daily insulin treatment that includes having an assigned "correction factor" for managing hyperglycemia.
- Age 18-75 years, inclusive.
- Random serum C-peptide concentration < 0.5 ng/mL.
- Willingness to follow all study procedures, including attending all clinic visits.
- Subject has provided informed consent as evidenced by a signed/dated informed consent form completed before any trial-related activities occur.
Who cannot join
- Pregnancy: For women of childbearing potential, there is a requirement for a negative urine pregnancy test and for agreement to use contraception throughout the study and for 7 days after the last dose of study glucagon. Acceptable contraception includes birth control pill / patch / vaginal ring, Depo-Provera, Norplant, an IUD, the double barrier method (the woman uses a diaphragm and spermicide and the man uses a condom), or abstinence.
- Breastfeeding: Nursing mothers will be allowed into the study. However, breast feeding during the during inpatient study visits and for 48 hours after each dose of study drug is not allowed.
- HbA1c >9.0% at Screening.
- BMI > 40 kg/m2.
- Renal insufficiency (serum creatinine greater than 3.0 mg/dL) or end-stage renal disease. requiring renal replacement therapy.
- Serum ALT or AST equal to or greater than 3 times the upper limit of normal.
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- Hepatic synthetic insufficiency as defined as a serum albumin of less than 3.0 g/dL.
- Hematocrit of less than or equal to 30%.
- BP readings at Screening where SBP <90 or >150 mm Hg, and DBP <50 or >100 mm Hg.
- Clinically significant ECG abnormalities.
- Use of > 2.0 U/kg total insulin dose per day.
- Inadequate venous access.
- Congestive heart failure, NYHA class III or IV.
- History of myocardial infarction, unstable angina, or revascularization within the past 6 months.
- History of a cerebrovascular accident in past 6 months or with major neurological deficits.
- Active malignancy within 5 years from Screening, except basal cell or squamous cell skin cancers. 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 x 10e9 per liter.
- History of pheochromocytoma or disorder with increased risk of pheochromocytoma (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 \& trehalose) in the investigational formulation.
- History of glycogen storage disease.
- Subject tests positive for HIV, HCV or HBV infection (HBsAg+) at Screening.
- Active substance or alcohol abuse (more than 21 drinks/wk. for males or 14 drinks/wk. for females). Subjects reporting active marijuana use or testing positive for tetrahydrocannabinol (THC) via rapid urine test will be allowed to participate in the study at the discretion of the Investigator.
- Administration of glucagon within 28 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 reason the Investigator deems exclusionary.
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
United States4 sites
Atlanta Diabetes Associates
Atlanta, Georgia, 30318
ProSciento, Inc.
Chula Vista, California, 91911
Rainier Clinical Research Center, Inc.
Renton, Washington, 98057
Diablo Clinical Research, Inc.
Walnut Creek, California, 94598
Canada2 sites
Altasciences Algorithme Pharma
Montreal, Quebec, H3P 3P1
LMC ESD, Inc.
Toronto, Ontario, M4G 3E8
About this study
Official title: G-Pen™ (Glucagon Injection) Compared to Lilly Glucagon (Glucagon for Injection [RDNA Origin]) for Induced Hypoglycemia Rescue in Adults With T1D: a Phase 3 B Multi-Centered, Randomized, Controlled, Single Blind, 2-Way Crossover Study to Evaluate Efficacy and Safety
This is a non-inferiority, 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 Lilly 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 hypoglycemia through IV administration of regular insulin diluted in normal saline. After a hypoglycemic state with plasma glucose < 50 mg/dL is verified, the subject is administered a dose of G-Pen or Lilly Glucagon via subcutaneous injection. Plasma glucose levels are monitored for up to 180 minutes post-dosing, with a value of >70.0 mg/dL 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 procedure 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, Lilly 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
Lilly GlucagonDrug
Also called GEK
1 mg subcutaneous injection of Lilly Glucagon (glucagon injection [RNDA Origin])
| Study group | Role | What they receive |
|---|---|---|
| G-Pen followed by Lilly Glucagon | Other | 1 mg G-Pen at the first treatment visit followed by 1 mg Lilly Glucagon at the second treatment visit Receives: Drug: G-Pen; Drug: Lilly Glucagon |
| Lilly Glucagon followed by G-Pen | Other | 1 mg Lilly Glucagon at the first treatment visit followed by 1 mg G-Pen at the second treatment visit Receives: Drug: G-Pen; Drug: Lilly Glucagon |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With a Positive Glucose Response
Increase in plasma glucose concentration from below 50.0 mg/dL to greater than 70.0 mg/dL within 30 minutes after receiving glucagon
Measured: 0 to 30 minutes post dose
Secondary outcomes (13)
Time for Positive Glucose Response
Time from administration of glucagon for plasma glucose to rise from below 50.0 mg/dL to above 70.0 mg/dL
Measured: 0 to 180 minutes post dose
Number of Subjects With a Positive Response for the Combination Endpoint: Positive Glucose Response/Positive Glucose Increase
A positive response for this endpoint is a return of plasma glucose to > 70 mg/dL or an increase in plasma glucose by ≥20 mg/dL within 30 minutes after receiving glucagon
Measured: 0 to 30 minutes post dose
Number of Subjects With a Positive Glucose Increase
Increase in plasma glucose by ≥ 20.0 mg/dL within 30 minutes after receiving glucagon
Measured: 0 to 30 minutes post dose
Time for Positive Glucose Increase
Time from administration of glucagon for plasma glucose to increase by ≥20 mg/dL from baseline
Measured: 0 to 180 minutes post dose
Number of Subjects With a Positive Response for the Combination Endpoint: Positive Glucose Response/Relief of Neuroglycopenic Symptoms
A positive response for this endpoint is a return of plasma glucose to > 70 mg/dL or clearance of all neuroglycopenic symptoms of hypoglycemia within 30 minutes after receiving glucagon. Four symptoms were assessed: dizziness, blurred vision, difficulty in thinking and faintness.
Measured: 0 to 30 minutes post dose
Number of Subjects With Relief of Neuroglycopenic Symptoms
Clearance of all neuroglycopenic symptoms of hypoglycemia within 30 minutes after receiving glucagon. Four symptoms were assessed: dizziness, blurred vision, difficulty in thinking and faintness.
Measured: 0 to 30 minutes post dose
Time to Resolution of Autonomic Symptoms
Time from administration of glucagon to complete resolution of 4 autonomic symptoms of hypoglycemia. Symptoms included: sweating, tremor, palpitations and feeling of nervousness.
Measured: 0 to 180 minutes post dose
Time to Resolution of Neuroglycopenic Symptoms
Time from administration of glucagon to complete resolution of 4 neuroglycopenic symptoms of hypoglycemia. Four symptoms were assessed: dizziness, blurred vision, difficulty in thinking and faintness.
Measured: 0 to 180 minutes post dose
Time to Resolution of the Feeling of Hypoglycemia
Time from administration of glucagon to resolution of the overall sensation of hypoglycemia. Subjects were asked to answer yes/no to the question, "Do you feel hypoglycemic?" The time point as which the subject first answered "no" was considered the time of resolution.
Measured: 0 to 180 minutes post dose
Glucose AUC
Area under the curve for plasma glucose.
Measured: 0 to 180 minutes post dose - Blood samples for assessment of blood glucose concentration were collected every 5 minutes post-dose to 90 minutes, and then at 120, 150 and 180 minutes post dose.
Glucose Cmax
Maximum concentration of plasma glucose.
Measured: 0 to 180 minutes post dose - Blood samples for assessment of blood glucose concentration were collected every 5 minutes post-dose to 90 minutes, and then at 120, 150 and 180 minutes post dose.
Glucose Tmax
Time to maximum concentration of plasma glucose. Blood samples for assessment of blood glucose concentration were collected every 5 minutes post-dose to 90 minutes, and then at 120, 150 and 180 minutes post dose.
Measured: 0 to 180 minutes post dose
Glucagon Preparation and Administration Time
Time required to prepare and inject glucagon as measured between a "decision to dose" and completion of the injection
Measured: 0 to 5 minutes pre-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2018
- Study start23 Jan 2018
- Primary completion18 Apr 2018
- Study completion3 May 2018
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
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- Xeris Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- SGS S.A., Integrated Medical Development
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03439072
- Sponsor's protocol ID
- XSGP-303
- Status last verified
- Feb 2020
- First submitted
- 13 Feb 2018
- Last updated
- 17 Feb 2020
- 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
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2020. 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 Adults With T1D: a Phase 3 B Multi-Centered, Randomized, Controlled, Single Blind, 2-Way Crossover Study to Evaluate Efficacy and Safety
- ClinicalTrials.gov ID
- NCT03439072
- Acronym / sponsor ID
- XSGP-303
- Keywords
- glucagon, hypoglycemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- Xeris PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- SGS S.A., Integrated Medical Development
- Study start
- 23 Jan 2018 (actual)
- Primary completion
- 18 Apr 2018 (actual)
- Study completion
- 3 May 2018 (actual)
- First posted
- 20 Feb 2018 (actual)
- Results
- Posted 30 May 2019
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 non-inferiority, 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 Lilly 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 hypoglycemia through IV administration of regular insulin diluted in normal saline. After a hypoglycemic state with plasma glucose < 50 mg/dL is verified, the subject is administered a dose of G-Pen or Lilly Glucagon via subcutaneous injection. Plasma glucose levels are monitored for up to 180 minutes post-dosing, with a value of >70.0 mg/dL 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 procedure 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 Lilly Glucagon | Other | Drug: G-Pen, Drug: Lilly Glucagon1 mg G-Pen at the first treatment visit followed by 1 mg Lilly Glucagon at the second treatment visit |
| Lilly Glucagon followed by G-Pen | Other | Drug: G-Pen, Drug: Lilly Glucagon1 mg Lilly 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 females diagnosed with type 1 diabetes mellitus for at least 24 months.
- Current usage of daily insulin treatment that includes having an assigned "correction factor" for managing hyperglycemia.
- Age 18-75 years, inclusive.
- Random serum C-peptide concentration < 0.5 ng/mL.
- Willingness to follow all study procedures, including attending all clinic visits.
Key exclusion criteria (28 listed)
- Pregnancy: For women of childbearing potential, there is a requirement for a negative urine pregnancy test and for agreement to use contraception throughout the study and for 7 days after the last dose of study glucagon. Acceptable contraception includes birth control pill / patch / vaginal ring, Depo-Provera, Norplant, an IUD, the double barrier method (the woman uses a diaphragm and spermicide and the man uses a condom), or abstinence.
- Breastfeeding: Nursing mothers will be allowed into the study. However, breast feeding during the during inpatient study visits and for 48 hours after each dose of study drug is not allowed.
- HbA1c >9.0% at Screening.
- BMI > 40 kg/m2.
- Renal insufficiency (serum creatinine greater than 3.0 mg/dL) or end-stage renal disease. requiring renal replacement therapy.
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 Lilly Glucagon, Lilly Glucagon followed by G-Pen |
| Lilly GlucagonAlso: GEK1 mg subcutaneous injection of Lilly Glucagon (glucagon injection [RNDA Origin]) | Drug | G-Pen followed by Lilly Glucagon, Lilly Glucagon followed by G-Pen |
Primary outcome
Number of Subjects With a Positive Glucose Response
Time frame: 0 to 30 minutes post dose
Increase in plasma glucose concentration from below 50.0 mg/dL to greater than 70.0 mg/dL within 30 minutes after receiving glucagon
13 secondary outcomes
Time for Positive Glucose Response
Time frame: 0 to 180 minutes post dose
Number of Subjects With a Positive Response for the Combination Endpoint: Positive Glucose Response/Positive Glucose Increase
Time frame: 0 to 30 minutes post dose
Number of Subjects With a Positive Glucose Increase
Time frame: 0 to 30 minutes post dose
Time for Positive Glucose Increase
Time frame: 0 to 180 minutes post dose
Number of Subjects With a Positive Response for the Combination Endpoint: Positive Glucose Response/Relief of Neuroglycopenic Symptoms
Time frame: 0 to 30 minutes post dose
Number of Subjects With Relief of Neuroglycopenic Symptoms
Time frame: 0 to 30 minutes post dose
Time to Resolution of Autonomic Symptoms
Time frame: 0 to 180 minutes post dose
Time to Resolution of Neuroglycopenic Symptoms
Time frame: 0 to 180 minutes post dose
Time to Resolution of the Feeling of Hypoglycemia
Time frame: 0 to 180 minutes post dose
Glucose AUC
Time frame: 0 to 180 minutes post dose - Blood samples for assessment of blood glucose concentration were collected every 5 minutes post-dose to 90 minutes, and then at 120, 150 and 180 minutes post dose.
Glucose Cmax
Time frame: 0 to 180 minutes post dose - Blood samples for assessment of blood glucose concentration were collected every 5 minutes post-dose to 90 minutes, and then at 120, 150 and 180 minutes post dose.
Glucose Tmax
Time frame: 0 to 180 minutes post dose
Glucagon Preparation and Administration Time
Time frame: 0 to 5 minutes pre-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2020.
- 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.
6 sites in 2 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 Lilly Glucagon in people with Insulin Hypoglycemia and Type 1 Diabetes Mellitus, run by Xeris Pharmaceuticals at 6 sites in 2 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 28 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 17 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 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 30 May 2019). 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?
Number of Subjects With a Positive Glucose Response (time frame: 0 to 30 minutes post dose). 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 NCT03439072, 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 17 Feb 2020.