Hypoglycemia UnawarenessPhase 2NCT03490942
Glucagon Infusion in T1D Patients With Recurrent Severe Hypoglycemia: Effects on Counter-Regulatory Responses
A Phase 2 study testing Glucagon in people with Hypoglycemia Unawareness and Diabetes Mellitus, Type 1, run by Xeris Pharmaceuticals at 5 sites in United States.
Trial summary
This is a prospective, randomized, controlled, double-blind, parallel 4-group trial with the primary analysis after 4 weeks of treatment with continuous subcutaneous glucagon infusion (CSGI) or placebo. Read more about this study
- Who is it for?
- Ages 21 to 64 years
- Conditions the study is for
- Hypoglycemia Unawareness, Diabetes Mellitus, Type 1
- What is being tested?
- Glucagon
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 49 participants
- Where
- 5 sitesUnited States
- Study dates
- 15 Mar 2018to 10 Feb 2020
- Phase
- Phase 2
- 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 21 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Males or females diagnosed with type 1 diabetes mellitus for at least 24 months.
- Random serum C-peptide concentration < 0.5 ng/ml at Screening.
- Current use of multiple daily dosing insulin treatment < 1 U/(kg*day) total daily dose either administered with subcutaneous injections or continuous subcutaneous insulin infusion (CSII).
- Recurrent severe hypoglycemia as defined by minimally two events during the last year and at least one the last six months requiring not merely receiving third party intervention and either confirmation with a measured glucose < 50 mg/dl, or prompt recovery from impaired consciousness. Events must be documented in patient chart prior to study entry. Events induced as a part of clinical diagnostics or experimentation do not qualify.
- Performs monitoring of glucose minimally 3 times a day. Patients using continuous glucose monitoring for monitoring should continue to do so during the course of the study.
- Age 21-64 years, inclusive, at screening.
- Willingness to provide informed consent and follow all study procedures, including using the Medtronic smart phone application "iPRO2mylog" for diabetes data logging and attending all scheduled visits.
Who cannot join
- Subjects using CSII, who do not use a Medtronic pump.
- Hemoglobin A1c ≥9.0% at Screening.
- Chronic kidney disease stage 4 or 5.
- Hepatic disease, including serum alanine transaminase (ALT) or aspartate transaminase (AST) greater than or equal to 3 times the upper limit of normal; hepatic synthetic insufficiency as defined as serum albumin < 3.0 g/dL; or serum bilirubin > 2.0.
- Hematocrit of less than or equal to 30% at Screening.
- Blood pressure (BP) reading at Screening where systolic BP <90 or >150 mm Hg, or diastolic BP <50 or >100 mm Hg.
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- Clinically significant echocardiogram (ECG) abnormalities at Screening.
- Congestive heart failure, New York Heart Association (NYHA) class II, III or IV,
- History of myocardial infarction, unstable angina or revascularization within the past 6 months.
- History of a cerebrovascular accident.
- Current seizure disorder.
- History of pheochromocytoma or disorder with increased risk of pheochromocytoma (multiple endocrine neoplasia type 2, neurofibromatosis, or Von Hippel-Lindau disease).
- History of insulinoma.
- 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 bleeding disorder, treatment with warfarin, or platelet count below 50,000 at Screening.
- 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 in the investigational formulation.
- History of glycogen storage disease.
- Any concurrent illness, other than diabetes, that is not controlled by a stable therapeutic regimen.
- Whole blood donation of 1 pint (500 mL) within 8 weeks prior to Screening. Donations of plasma, packed red blood cells, platelets or quantities less than 500 mL are allowed at investigator discretion.
- Active substance or alcohol abuse (more than 21 drinks/wk. for males or 14 drinks/wk. for females). Subjects reporting active marijuana use and/or testing positive for tetrahydrocannabinol via rapid urine test will be allowed to participate in the study at the discretion of the investigator. Subjects positive for other drugs of abuse via rapid urine test who report use of a prescription or over-the-counter medication that would explain such a finding will be allowed to participate at the discretion of the investigator.
- Administration of glucagon within 14 days of Screening.
- Pregnant and/or Lactating. For subjects of childbearing potential, there is a requirement for a negative urine pregnancy test and for agreement to use contraception and to refrain from breast feeding during the study and for at least 1 month after participating in the study. Acceptable contraception includes birth control pill / patch / vaginal ring, Depo-Provera, Norplant, an intra-uterine device, the double barrier method (the female uses a diaphragm and spermicide and the male uses a condom), or abstinence.
- Inadequate venous access.
- Participation in other studies involving administration of an investigational drug or interventional device within 30 days or 5 half-lives, whichever is longer, before Screening for the current study and during the four weeks of study product administration in the current study.
- Any reason the principal investigator deems exclusionary.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Emory University - Grady Memorial Hospital
Atlanta, Georgia, 30303
Atlanta Diabetes Associates
Atlanta, Georgia, 30318
University of Alabama, Birmingham
Birmingham, Alabama, 35294
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
University of California, San Diego
San Diego, California, 92037
About this study
Official title: Fixed Rate Continuous Subcutaneous Glucagon Infusion (CSGI) vs Placebo in Type 1 Diabetes Mellitus Patients With Recurrent Severe Hypoglycemia: Effects on Counter-Regulatory Responses to Insulin-Induced Hypoglycemia
This is a prospective, randomized, controlled, double-blind, parallel 4-group trial with the primary analysis after 4 weeks of treatment with continuous subcutaneous glucagon infusion (CSGI) or placebo. After a 1-week qualification on continuous glucose monitoring (CGM), subjects will have their baseline hypoglycemia counter-regulatory response hormones quantified using a step-wise hypoglycemia induction procedure. Subjects meeting eligibility requirements will be randomized to 1 of 4 treatment groups, 2 glucagon, 2 placebo. Subjects will receive blinded study drug for 4 weeks, and they will be followed for an additional 26 weeks post-treatment. Subjects' counter-regulatory hormone response will be measured at baseline, the end of treatment (4 weeks), and 13 and 26 weeks after treatment ends.
- Being tested
- Glucagon, Placebo
- Keywords
- glucagon, hypoglycemia counter-regulation
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GlucagonDrug
Also called CSI-Glucagon, CGSI
CSI-Glucagon is a room temperature stable, non-aqueous, liquid formulation of glucagon.
PlaceboDrug
The placebo solution is a non-active formulation containing excipients only.
| Study group | Role | What they receive |
|---|---|---|
| CSGI high infusion rate | Experimental | Glucagon given as a continuous subcutaneous infusion for 28 days Receives: Drug: Glucagon |
| CSGI low infusion rate | Experimental | Glucagon given as a continuous subcutaneous infusion for 28 days Receives: Drug: Glucagon |
| Placebo high infusion rate | Placebo comparator | Placebo given as a continuous subcutaneous infusion for 28 days Receives: Drug: Placebo |
| Placebo low infusion rate | Placebo comparator | Placebo given as a continuous subcutaneous infusion for 28 days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma Epinephrine
Plasma epinephrine concentration after 30 minutes of induced hypoglycemia. Change from baseline to the end of treatment will be assessed.
Measured: 0-30 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2018
- Study start15 Mar 2018
- Primary completion4 Nov 2019
- Study completion10 Feb 2020
Why it stopped: Primary endpoint was not met
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.
- Other trials for Hypoglycemia UnawarenessStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a prospective, randomized, controlled, double-blind, parallel 4-group trial with the primary analysis after 4 weeks treatment with CSGI or placebo.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Xeris Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Integrated Medical Development
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03490942
- Sponsor's protocol ID
- XSGO-AF01
- Status last verified
- May 2020
- First submitted
- 25 Mar 2018
- Last updated
- 21 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fixed Rate Continuous Subcutaneous Glucagon Infusion (CSGI) vs Placebo in Type 1 Diabetes Mellitus Patients With Recurrent Severe Hypoglycemia: Effects on Counter-Regulatory Responses to Insulin-Induced Hypoglycemia
- ClinicalTrials.gov ID
- NCT03490942
- Acronym / sponsor ID
- XSGO-AF01
- Keywords
- glucagon, hypoglycemia counter-regulation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Primary endpoint was not met
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Xeris PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- Integrated Medical Development
- Study start
- 15 Mar 2018 (actual)
- Primary completion
- 4 Nov 2019 (actual)
- Study completion
- 10 Feb 2020 (actual)
- First posted
- 6 Apr 2018 (actual)
- Results
- Posted 21 Feb 2021
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 prospective, randomized, controlled, double-blind, parallel 4-group trial with the primary analysis after 4 weeks of treatment with continuous subcutaneous glucagon infusion (CSGI) or placebo. After a 1-week qualification on continuous glucose monitoring (CGM), subjects will have their baseline hypoglycemia counter-regulatory response hormones quantified using a step-wise hypoglycemia induction procedure. Subjects meeting eligibility requirements will be randomized to 1 of 4 treatment groups, 2 glucagon, 2 placebo. Subjects will receive blinded study drug for 4 weeks, and they will be followed for an additional 26 weeks post-treatment. Subjects' counter-regulatory hormone response will be measured at baseline, the end of treatment (4 weeks), and 13 and 26 weeks after treatment ends.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
- Model description
- This is a prospective, randomized, controlled, double-blind, parallel 4-group trial with the primary analysis after 4 weeks treatment with CSGI or placebo.
| Arm | Type | Receives |
|---|---|---|
| CSGI high infusion rate | Experimental | Drug: GlucagonGlucagon given as a continuous subcutaneous infusion for 28 days |
| CSGI low infusion rate | Experimental | Drug: GlucagonGlucagon given as a continuous subcutaneous infusion for 28 days |
| Placebo high infusion rate | Placebo comparator | Drug: PlaceboPlacebo given as a continuous subcutaneous infusion for 28 days |
| Placebo low infusion rate | Placebo comparator | Drug: PlaceboPlacebo given as a continuous subcutaneous infusion for 28 days |
Who may qualify
- Ages
- 21 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Males or females diagnosed with type 1 diabetes mellitus for at least 24 months.
- Random serum C-peptide concentration < 0.5 ng/ml at Screening.
- Current use of multiple daily dosing insulin treatment < 1 U/(kg*day) total daily dose either administered with subcutaneous injections or continuous subcutaneous insulin infusion (CSII).
- Recurrent severe hypoglycemia as defined by minimally two events during the last year and at least one the last six months requiring not merely receiving third party intervention and either confirmation with a measured glucose < 50 mg/dl, or prompt recovery from impaired consciousness. Events must be documented in patient chart prior to study entry. Events induced as a part of clinical diagnostics or experimentation do not qualify.
- Performs monitoring of glucose minimally 3 times a day. Patients using continuous glucose monitoring for monitoring should continue to do so during the course of the study.
Key exclusion criteria (26 listed)
- Subjects using CSII, who do not use a Medtronic pump.
- Hemoglobin A1c ≥9.0% at Screening.
- Chronic kidney disease stage 4 or 5.
- Hepatic disease, including serum alanine transaminase (ALT) or aspartate transaminase (AST) greater than or equal to 3 times the upper limit of normal; hepatic synthetic insufficiency as defined as serum albumin < 3.0 g/dL; or serum bilirubin > 2.0.
- Hematocrit of less than or equal to 30% at Screening.
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 |
|---|---|---|
| GlucagonAlso: CSI-Glucagon, CGSICSI-Glucagon is a room temperature stable, non-aqueous, liquid formulation of glucagon. | Drug | CSGI high infusion rate, CSGI low infusion rate |
| PlaceboThe placebo solution is a non-active formulation containing excipients only. | Drug | Placebo high infusion rate, Placebo low infusion rate |
Primary outcome
Plasma Epinephrine
Time frame: 0-30 minutes
Plasma epinephrine concentration after 30 minutes of induced hypoglycemia. Change from baseline to the end of treatment will be assessed.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Glucagon in people with Hypoglycemia Unawareness and Diabetes Mellitus, Type 1, run by Xeris Pharmaceuticals at 5 sites in United States.
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 7 inclusion and 26 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: stopped early, as of the sponsor's last update on 21 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 21 Feb 2021). 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?
Plasma Epinephrine (time frame: 0-30 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 Feb 2021.