HypoglycemiaPhase 2NCT03841526
Glucagon Ready-to-Use (RTU) for Prevention of Exercise-Induced Hypoglycemia During Aerobic Exercise in Adults With T1D
A Phase 2 study testing Glucagon RTU Injection With Insulin Pump Reduction and Glugaon RTU Injection Without Insulin Pump Reduction in people with Hypoglycemia, run by Xeris Pharmaceuticals at 1 site in Canada.
Trial summary
This study is a randomized, placebo-controlled, double-blind, 2-treatment, 2-period, crossover comparison in a clinical research center (CRC) setting, followed by a randomized, placebo-controlled, double-blinded, 2-arm parallel comparison with a third open-label arm in an outpatient setting. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Hypoglycemia
- What is being tested?
- Glucagon RTU Injection With Insulin Pump Reduction and Glugaon RTU Injection Without Insulin Pump Reduction
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteCanada
- Study dates
- 22 Aug 2019to 2 Apr 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 18 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Clinical diagnosis of presumed autoimmune type 1 diabetes, receiving daily insulin via continuous subcutaneous insulin infusion.
- Age 18 to < 65 years.
- Duration of type 1 diabetes ≥ 2 years.
- Random C-peptide < 0.6 ng/mL (<198 pmol/L).
- Using insulin therapy by continuous subcutaneous insulin infusion pump for at least 6 months.
- History of exercise-related hypoglycemia.
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- Performs aerobic exercise regularly (2-3 times per week), and desires to exercise per American Diabetes Association guidelines (150 minutes per week). Examples of aerobic exercise include: power walking, hiking, running/jogging, cycling, swimming, cross country skiing, and aerobic fitness classes.
- Will abstain from the use of non-insulin diabetes therapies such as sodium glucose co-transporter 2, glucagon like peptide-1, and metformin for the duration of the study.
- Subject must be willing to adhere to the protocol requirements for the duration of the study.
- Subject has provided informed consent as evidenced by a signed/dated informed consent form completed before any trial-related activities occur.
Who cannot join
- Frequently experience hyperglycemia with exercise, in the clinical judgement of the investigator.
- Pregnant and/ or Nursing: For female 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 week after the last dose of study drug. Acceptable contraception includes birth control pill / patch / vaginal ring, Depo-Provera, Norplant, an intra-uterine device, the double barrier method (the woman uses a diaphragm and spermicide and the man uses a condom), or abstinence.
- One or more severe hypoglycemic episodes in the past 12 months (as defined by an episode that required third party assistance for treatment).
- Uses inhaled insulin.
- Hemoglobin A1c > 9.0% at Screening.
- Renal insufficiency (serum creatinine greater than 3 mg/dL (0.17 mmol/L)).
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- Serum alanine aminotransferase or aspartate aminotransferase 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 mg/dL (0.17 mmol/L); or serum bilirubin greater than 2 mg/dL (0.11 mmol/L).
- Hematocrit of less than or equal to 30%.
- Mean of triplicate blood pressure (BP) readings at Screening where systolic BP <90 or >150 mm Hg, or diastolic BP <50 or >100 mm Hg.
- Clinically significant electrocardiogram abnormalities.
- 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 III or IV.
- Active malignancy within 5 years from Screening, except basal cell or squamous cell skin cancers.
- Major surgical operation within 90 days prior to screening, or planned surgical operation during the study.
- History of seizure disorders.
- Bleeding disorder, treatment with warfarin or any anticoagulants, or platelet count below 50,000 mm3 at Screening.
- History of pheochromocytoma or disorder with increased risk of pheochromocytoma (multiple endocrine neoplasia type 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 (dimethylsulfoxide, mannitol, \& trehalose) in the investigational formulation.
- History of glycogen storage disease.
- Subject tests positive for human immunodeficiency virus, hepatitis C virus, or active hepatitis B virus infection at Screening.
- Any concurrent illness, other than diabetes, that is not controlled by a stable therapeutic regimen.
- Active substance or alcohol abuse, in the opinion of the investigator. Subjects reporting active marijuana use or testing positive for tetrahydrocannabinol via rapid urine test will be allowed to participate in the study at the discretion of the investigator.
- Participation in other studies involving administration of an investigational therapeutic agent (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
1 site in 1 country.
About this study
Official title: Phase 2 Randomized Placebo-Controlled Double-Blind Parallel Study to Evaluate Glucagon RTU (Glucagon Injection) Compared to Standard of Care for Prevention of Exercise-Induced Hypoglycemia During Regular Aerobic Exercise in Adults With T1D
This study is a randomized, placebo-controlled, double-blind, 2-treatment, 2-period, crossover comparison in a clinical research center (CRC) setting, followed by a randomized, placebo-controlled, double-blinded, 2-arm parallel comparison with a third open-label arm in an outpatient setting. The purpose of the study is to evaluate the preliminary efficacy and safety of Glucagon Ready-to-Use [RTU] to prevent exercise-induced hypoglycemia (EIH) in adults with Type 1 diabetes mellitus (T1D), who perform regular, moderate-to-high intensity aerobic exercise.
Read the detailed description
There were 2 phases of this study: CRC and Outpatient. The initial posting of this study reflected the 3 treatment arms included in the Outpatient Phase of the study, without including the CRC and Outpatient Phases separately.
CRC Phase:
The CRC Phase was comprised of 2 visits that included daytime exercise sessions at the CRC or a comparable setting. Subjects were randomized to receive their first treatment at Visit 3 and crossed over (2 to 28 day washout) to their second treatment at Visit 4. The treatments were a single treatment with 30 microliters of either Glucagon RTU (0.15 mg) or placebo with a 50% insulin pump reduction. Blood glucose was assessed 15 minutes prior to the start of exercise, at the start of exercise, and then 15, 30, 45, 60, and 75 minutes from the start of exercise.
Outpatient Phase:
After completion of the CRC Phase, subjects entered the 12-week Outpatient Phase. Subjects were to maintain a weekly exercise average of 2 to 3 sessions of at least 30 minutes duration. Subjects were assigned randomly in 1:1:1 ratio to administer 30 microliters of one of the following prior to the exercise sessions: Glucagon RTU (0.15 mg) with a 50% insulin pump reduction, placebo with a 50% pump reduction or Glucagon RTU (0.15 mg) without an insulin pump reduction. Blood glucose was assessed 15 minutes prior to the start of exercise, just before exercise, after 30 minutes of exercise, at the end of exercise (if longer than 30 minutes), and 30 minutes post-exercise.
- Conditions
- Hypoglycemia
- Being tested
- Glucagon RTU Injection With Insulin Pump Reduction, Vehicle for Glucagon RTU Injection With Insulin Pump Reduction, Glugaon RTU Injection Without Insulin Pump Reduction
- Keywords
- Exercise, Glucagon, Insulin
- Medical subject headings
- Hypoglycemia, Motor Activity, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Glucagon RTU Injection With Insulin Pump ReductionDrug
Also called XP-3994
0.15 mg injection with 50% pump reduction
Vehicle for Glucagon RTU Injection With Insulin Pump ReductionOther
Also called Placebo
vehicle injection with 50% pump reduction
Glugaon RTU Injection Without Insulin Pump ReductionDrug
Also called XP-3994
0.15 mg injection without pump reduction
| Study group | Role | What they receive |
|---|---|---|
| CRC Phase: Glucagon RTU With Insulin Pump Reduction | Experimental | CRC Phase: 2-arm randomized double-blind crossover, Glucagon RTU Injection 30 microliters of 0.15 mg injection with 50% reduction in the insulin pump Receives: Drug: Glucagon RTU Injection With Insulin Pump Reduction |
| CRC Phase: Vehicle for Glucagon RTU With Insulin Pump Reduction | Placebo comparator | CRC Phase: 2-arm randomized double-blind crossover, Vehicle for Glucagon RTU Injection 30 microliters vehicle with 50% reduction in the insulin pump Receives: Other: Vehicle for Glucagon RTU Injection With Insulin Pump Reduction |
| Outpatient Phase: Glucagon RTU With Insulin Pump Reduction | Experimental | Outpatient Phase: 3-arm randomized comparison (2-arm double-blind, 1-arm open-label), Glucagon RTU Injection 30 microliters of 0.15 mg injection with 50% reduction in the insulin pump (double-blind arm) Receives: Drug: Glucagon RTU Injection With Insulin Pump Reduction |
| Outpatient Phase: Vehicle for Glucagon RTU With Insulin Pump Reduction | Placebo comparator | Outpatient Phase: 3-arm randomized comparison (2-arm double-blind, 1-arm open-label), Vehicle for Glucagon RTU Injection 30 microliters vehicle with 50% reduction in the insulin pump (double-blind arm) Receives: Other: Vehicle for Glucagon RTU Injection With Insulin Pump Reduction |
| Outpatient Phase: Glucagon RTU Without Insulin Pump Reduction | Experimental | Outpatient Phase: 3-arm randomized comparison (2-arm double-blind, 1-arm open-label), Glucagon RTU Injection 30 microliters of 0.15 mg injection without a reduction in the insulin pump (open-label arm) Receives: Drug: Glugaon RTU Injection Without Insulin Pump Reduction |
What is being measured
The primary outcome is the main question the study is designed to answer.
Outpatient Phase: Incidence Rate of Hypoglycemia During and After Moderate to High Intensity Aerobic Exercise.
Mean incidence rate of hypoglycemia during and after sessions of moderate to high intensity aerobic exercise in 12-week Outpatient Phase. Incidence rate is defined as the number of hypoglycemic events divided by the total number of qualified exercise sessions, assessed at group level.
Qualified exercise session is: (1) confirmed blood glucose of 100-180 mg/dL prior to start of exercise, (2) self-administered study drug no more than 10 min prior to exercise (5 min target), (3) conducted a protocol allowed exercise of moderate to high intensity for at least 30 min and no longer than 75 min, and (4) achieved a target heart rate of 80% of maximum calculated heart rate at least once during session.
Exercise sessions were to occur at least 2-3 times per week. Only 1 qualified exercise session/subject/day was included in the analysis (the first if >1).
Hypoglycemic event defined as any hypoglycemic event occurring within 30 (+2) min after completion of a qualified exercise session.
Measured: Daily; During the 12-week Outpatient Phase qualified exercise sessions were assessed daily and associated hypoglycemia events were assessed continuously during and within the 30 (+2) minute period following a qualified exercise session.
Outpatient Phase: Mean Number of Hypoglycemic Events
Outpatient Phase: Mean number of hypoglycemic events associated with the qualified exercise sessions, assessed at group level.
A qualified exercise session was defined as one were (1) a confirmed blood glucose value of 100-180 mg/dL prior to start of exercise, (2) self-administered the study drug no more than 10 minutes prior to exercise (5 minutes was the target), (3) conducted a protocol allowed exercise for moderate to high intensity for at least 30 minutes and no longer than 75 minutes, and (4) achieved a target heart rate of 80% of maximum calculated heart rate at least once during the session.
A hypoglycemic event was defined as any hypoglycemic event occurring during or within 30 (+2) minutes after completion of a qualified exercise session.
Exercise sessions were expected to occur at least 2 to 3 times per week. Only 1 qualified exercise session per subject per day was included in the analysis (the first if >1).
Measured: Daily; During the 12-week Outpatient Phase qualified exercise sessions were assessed daily and associated hypoglycemia events were assessed continuously throughout the 30 (+2) minute period following a qualified exercise session.
Outpatient Phase: Mean Number of Qualified High Intensity Aerobic Exercise Sessions
Outpatient Phase: Mean number of qualified exercise sessions, assessed at group level.
A qualified exercise session was defined as one were (1) a confirmed blood glucose value of 100-180 mg/dL prior to start of exercise, (2) self-administered the study drug no more than 10 minutes prior to exercise (5 minutes was the target), (3) conducted a protocol allowed exercise for moderate to high intensity for at least 30 minutes and no longer than 75 minutes, and (4) achieved a target heart rate of 80% of maximum calculated heart rate at least once during the session.
Exercise sessions were expected to occur at least 2 to 3 times per week. Only 1 qualified exercise session per subject per day was included in the analysis (the first if >1).
Measured: Daily; During the 12-week Outpatient Phase the occurrence of qualified exercise sessions were assessed daily.
Secondary outcomes (6)
CRC Phase: Interstitial Glucose Below Target Range
Analysis of interstitial glucose (IG) was performed by treatment, independent of the order of treatment during the randomized cross-over CRC Phase. The number of participants are categorized by the following IG levels:
Below range, as defined by IG <= 70 mg/dl (<=3.89 mmol/L); Between range, as defined by IG between 54 to 70 mg/dL (3 to 3.89 mmol/L); Below range, as defined by IG <54 mg/dL (<3 mmol/L)
Measured: Visit 3 (Day 1) and Visit 4 (Day 3 or any day up to Day 29); Assessed continuously 0-300 minutes following the start of the exercise session corresponding to each of the treatments during the corresponding in-clinic visit during the CRC Phase.
Outpatient Phase: Interstitial Glucose Levels Below Target Range
Analysis of interstitial glucose (IG) was performed by treatment, during the randomized Outpatient Phase. The number of participants are categorized by the following IG levels:
Below range, as defined by IG <= 70 mg/dl (<=3.89 mmol/L); Between range, as defined by IG between 54 to 70 mg/dL (3 to 3.89 mmol/L); Below range, as defined by IG <54 mg/dL (<3 mmol/L)
Measured: Visit 3 (Day 1) and Visit 4 (Day 3 or any day up to Day 29); Assessed continuously 0-300 minutes following the start of each qualified exercise session corresponding to each of the treatments during the Outpatient Phase.
Outpatient Phase: Insulin Use Change From Baseline
Insulin use as reported by subject as Change from Outpatient Phase Baseline at Study Weeks 4, 8, and 12
Measured: Insulin use measured continuously from Study Baseline to End of Study and assessed during Outpatient Phase as Change from Outpatient Phase Baseline at Study Weeks 4, 8, and 12
Outpatient Phase: Barriers to Physical Activity Diabetes (Type 1): BAPAD-1 Change From Baseline
Change from Baseline to End of the Outpatient Phase in Score on Barriers to Physical Activity in Type 1 Diabetes (BAPAD-1) Questionnaire A total of 12 factors were scored from 1=unlikely (min.) to 7=extremely likely (max.) for their propensity to keep the subject from practicing regular physical exercise during the next 6 months. Lower scores are considered better, while higher scores are considered worse outcomes. The higher the score (1 to 7), the less likely the subject was to engage in exercise.
The mean of the scores of the 12 factors were calculated for each subject and the overall mean for the subjects was calculated at a group level with overall mean and standard deviation calculated at Baseline (Visit 3) and Follow-up/Early Termination (Visit 11) to calculate change from Baseline. Subject level and overall means could range from 1 to 7.
Measured: Baseline to End of Study measured at Outpatient Phase Baseline (Visit 3, Day 1) and Follow-up (Visit 11, 14-21 days after last exercise session, up to Day 134) or Early Termination (at time of discontinuation)
Outpatient Phase: HFS-II Overall Score Change From Baseline
Change from Baseline in Score on Hypoglycemia Fear Survey-II (HFS-II)
A total of 33 items were scored from 0=never (min.) to 4=almost always (max.) for how often in the past 6 months they had done the following:
Behavior (15 items): things that people with diabetes often do to avoid low blood sugar.
Worry (18 items): things that people with diabetes often worry about because of low blood sugar.
Lower scores are considered better outcomes, higher scores are considered worse outcomes.
The higher the score (0 to 4), the greater the subject's fear of hypoglycemia. The mean of the scores of the 33 items were calculated for each subject and the overall mean for the subjects was calculated at a group level with overall mean and standard deviation calculated at Baseline (Visit 3) and Follow-up/Early Termination (Visit 11) to calculate change from Baseline. Subject level and overall means could range from 0 to 4.
Measured: Baseline to End of Study measured at Outpatient Phase Baseline (Visit 3, Day 1) and Follow-up (Visit 11, 14-21 days after last exercise session, up to Day 134) or Early Termination (at time of discontinuation)
Outpatient Phase: Hypoglycemic Confidence Scale (HCS) Change From Baseline
Change from Baseline in Score on Hypoglycemia Confidence Scale (HCS)
The 9-item scale assessed a subject's confidence about safety regarding hypoglycemia. The questionnaire had 4 responses possible for each question, ranging from 1=not confident at all (min.) to 4=very confident (max.). Higher scores are considered better outcomes, while lower scores are considered worse outcomes. The lower the score (1 to 4), the less likely the subject was to engage in exercise.
The mean of the scores of the 9 items were calculated for each subject and the overall mean for the subjects was calculated at a group level with overall mean and standard deviation calculated at Baseline (Visit 3) and Follow-up/Early Termination (Visit 11) to calculate change from Baseline. Subject level and overall means could range from 1 to 4.
Measured: Baseline to End of Study measured at Outpatient Phase Baseline (Visit 3, Day 1) and Follow-up (Visit 11, 14-21 days after last exercise session, up to Day 134) or Early Termination (at time of discontinuation)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2019
- Study start22 Aug 2019
- Primary completion2 Apr 2020
- Study completion2 Apr 2020
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- CRC Phase: randomized, placebo-controlled, double-blind, two-treatment, two-period, crossover comparison in a clinical research center (CRC) setting. The subjects were re-randomized into the Outpatient Phase: randomized, placebo-controlled, partially double-blind, 3-arm parallel comparison in an outpatient setting.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Xeris Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Khaled Junaidi, MD, Study chair, Xeris Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03841526
- Sponsor's protocol ID
- XSMP-204
- Status last verified
- Aug 2023
- First submitted
- 12 Feb 2019
- Last updated
- 22 Aug 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Aronson R, Riddell MC, Conoscenti V, Junaidi MK. Effect of Mini-Dose Ready-to-Use Liquid Glucagon on Preventing Exercise-Associated Hypoglycemia in Adults With Type 1 Diabetes. Diabetes Care. 2023 Apr 1;46(4):765-772. doi: 10.2337/dc22-1145.
PubMed 36689626
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Randomized Placebo-Controlled Double-Blind Parallel Study to Evaluate Glucagon RTU (Glucagon Injection) Compared to Standard of Care for Prevention of Exercise-Induced Hypoglycemia During Regular Aerobic Exercise in Adults With T1D
- ClinicalTrials.gov ID
- NCT03841526
- Acronym / sponsor ID
- XSMP-204
- Conditions
- Hypoglycemia
- Keywords
- Exercise, Glucagon, Insulin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Xeris PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 22 Aug 2019 (actual)
- Primary completion
- 2 Apr 2020 (actual)
- Study completion
- 2 Apr 2020 (actual)
- First posted
- 15 Feb 2019 (actual)
- Results
- Posted 25 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a randomized, placebo-controlled, double-blind, 2-treatment, 2-period, crossover comparison in a clinical research center (CRC) setting, followed by a randomized, placebo-controlled, double-blinded, 2-arm parallel comparison with a third open-label arm in an outpatient setting. The purpose of the study is to evaluate the preliminary efficacy and safety of Glucagon Ready-to-Use [RTU] to prevent exercise-induced hypoglycemia (EIH) in adults with Type 1 diabetes mellitus (T1D), who perform regular, moderate-to-high intensity aerobic exercise.
Detailed description
There were 2 phases of this study: CRC and Outpatient. The initial posting of this study reflected the 3 treatment arms included in the Outpatient Phase of the study, without including the CRC and Outpatient Phases separately.
CRC Phase:
The CRC Phase was comprised of 2 visits that included daytime exercise sessions at the CRC or a comparable setting. Subjects were randomized to receive their first treatment at Visit 3 and crossed over (2 to 28 day washout) to their second treatment at Visit 4. The treatments were a single treatment with 30 microliters of either Glucagon RTU (0.15 mg) or placebo with a 50% insulin pump reduction. Blood glucose was assessed 15 minutes prior to the start of exercise, at the start of exercise, and then 15, 30, 45, 60, and 75 minutes from the start of exercise.
Outpatient Phase:
After completion of the CRC Phase, subjects entered the 12-week Outpatient Phase. Subjects were to maintain a weekly exercise average of 2 to 3 sessions of at least 30 minutes duration. Subjects were assigned randomly in 1:1:1 ratio to administer 30 microliters of one of the following prior to the exercise sessions: Glucagon RTU (0.15 mg) with a 50% insulin pump reduction, placebo with a 50% pump reduction or Glucagon RTU (0.15 mg) without an insulin pump reduction. Blood glucose was assessed 15 minutes prior to the start of exercise, just before exercise, after 30 minutes of exercise, at the end of exercise (if longer than 30 minutes), and 30 minutes post-exercise.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
- Model description
- CRC Phase: randomized, placebo-controlled, double-blind, two-treatment, two-period, crossover comparison in a clinical research center (CRC) setting. The subjects were re-randomized into the Outpatient Phase: randomized, placebo-controlled, partially double-blind, 3-arm parallel comparison in an outpatient setting.
| Arm | Type | Receives |
|---|---|---|
| CRC Phase: Glucagon RTU With Insulin Pump Reduction | Experimental | Drug: Glucagon RTU Injection With Insulin Pump ReductionCRC Phase: 2-arm randomized double-blind crossover, Glucagon RTU Injection 30 microliters of 0.15 mg injection with 50% reduction in the insulin pump |
| CRC Phase: Vehicle for Glucagon RTU With Insulin Pump Reduction | Placebo comparator | Other: Vehicle for Glucagon RTU Injection With Insulin Pump ReductionCRC Phase: 2-arm randomized double-blind crossover, Vehicle for Glucagon RTU Injection 30 microliters vehicle with 50% reduction in the insulin pump |
| Outpatient Phase: Glucagon RTU With Insulin Pump Reduction | Experimental | Drug: Glucagon RTU Injection With Insulin Pump ReductionOutpatient Phase: 3-arm randomized comparison (2-arm double-blind, 1-arm open-label), Glucagon RTU Injection 30 microliters of 0.15 mg injection with 50% reduction in the insulin pump (double-blind arm) |
| Outpatient Phase: Vehicle for Glucagon RTU With Insulin Pump Reduction | Placebo comparator | Other: Vehicle for Glucagon RTU Injection With Insulin Pump ReductionOutpatient Phase: 3-arm randomized comparison (2-arm double-blind, 1-arm open-label), Vehicle for Glucagon RTU Injection 30 microliters vehicle with 50% reduction in the insulin pump (double-blind arm) |
| Outpatient Phase: Glucagon RTU Without Insulin Pump Reduction | Experimental | Drug: Glugaon RTU Injection Without Insulin Pump ReductionOutpatient Phase: 3-arm randomized comparison (2-arm double-blind, 1-arm open-label), Glucagon RTU Injection 30 microliters of 0.15 mg injection without a reduction in the insulin pump (open-label arm) |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Clinical diagnosis of presumed autoimmune type 1 diabetes, receiving daily insulin via continuous subcutaneous insulin infusion.
- Age 18 to < 65 years.
- Duration of type 1 diabetes ≥ 2 years.
- Random C-peptide < 0.6 ng/mL (<198 pmol/L).
- Using insulin therapy by continuous subcutaneous insulin infusion pump for at least 6 months.
Key exclusion criteria (27 listed)
- Frequently experience hyperglycemia with exercise, in the clinical judgement of the investigator.
- Pregnant and/ or Nursing: For female 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 week after the last dose of study drug. Acceptable contraception includes birth control pill / patch / vaginal ring, Depo-Provera, Norplant, an intra-uterine device, the double barrier method (the woman uses a diaphragm and spermicide and the man uses a condom), or abstinence.
- One or more severe hypoglycemic episodes in the past 12 months (as defined by an episode that required third party assistance for treatment).
- Uses inhaled insulin.
- Hemoglobin A1c > 9.0% 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 |
|---|---|---|
| Glucagon RTU Injection With Insulin Pump ReductionAlso: XP-39940.15 mg injection with 50% pump reduction | Drug | CRC Phase: Glucagon RTU With Insulin Pump Reduction, Outpatient Phase: Glucagon RTU With Insulin Pump Reduction |
| Vehicle for Glucagon RTU Injection With Insulin Pump ReductionAlso: Placebovehicle injection with 50% pump reduction | Other | CRC Phase: Vehicle for Glucagon RTU With Insulin Pump Reduction, Outpatient Phase: Vehicle for Glucagon RTU With Insulin Pump Reduction |
| Glugaon RTU Injection Without Insulin Pump ReductionAlso: XP-39940.15 mg injection without pump reduction | Drug | Outpatient Phase: Glucagon RTU Without Insulin Pump Reduction |
Primary outcome
Outpatient Phase: Incidence Rate of Hypoglycemia During and After Moderate to High Intensity Aerobic Exercise.
Time frame: Daily; During the 12-week Outpatient Phase qualified exercise sessions were assessed daily and associated hypoglycemia events were assessed continuously during and within the 30 (+2) minute period following a qualified exercise session.
Mean incidence rate of hypoglycemia during and after sessions of moderate to high intensity aerobic exercise in 12-week Outpatient Phase. Incidence rate is defined as the number of hypoglycemic events divided by the total number of qualified exercise sessions, assessed at group level. Qualified exercise session is: (1) confirmed blood glucose of 100-180 mg/dL prior to start of exercise, (2) self-administered study drug no more than 10 min prior to exercise (5 min target), (3) conducted a protocol allowed exercise of moderate to high intensity for at least 30 min and no longer than 75 min, and (4) achieved a target heart rate of 80% of maximum calculated heart rate at least once during session. Exercise sessions were to occur at least 2-3 times per week. Only 1 qualified exercise session/subject/day was included in the analysis (the first if >1). Hypoglycemic event defined as any hypoglycemic event occurring within 30 (+2) min after completion of a qualified exercise session.
Outpatient Phase: Mean Number of Hypoglycemic Events
Time frame: Daily; During the 12-week Outpatient Phase qualified exercise sessions were assessed daily and associated hypoglycemia events were assessed continuously throughout the 30 (+2) minute period following a qualified exercise session.
Outpatient Phase: Mean number of hypoglycemic events associated with the qualified exercise sessions, assessed at group level. A qualified exercise session was defined as one were (1) a confirmed blood glucose value of 100-180 mg/dL prior to start of exercise, (2) self-administered the study drug no more than 10 minutes prior to exercise (5 minutes was the target), (3) conducted a protocol allowed exercise for moderate to high intensity for at least 30 minutes and no longer than 75 minutes, and (4) achieved a target heart rate of 80% of maximum calculated heart rate at least once during the session. A hypoglycemic event was defined as any hypoglycemic event occurring during or within 30 (+2) minutes after completion of a qualified exercise session. Exercise sessions were expected to occur at least 2 to 3 times per week. Only 1 qualified exercise session per subject per day was included in the analysis (the first if >1).
Outpatient Phase: Mean Number of Qualified High Intensity Aerobic Exercise Sessions
Time frame: Daily; During the 12-week Outpatient Phase the occurrence of qualified exercise sessions were assessed daily.
Outpatient Phase: Mean number of qualified exercise sessions, assessed at group level. A qualified exercise session was defined as one were (1) a confirmed blood glucose value of 100-180 mg/dL prior to start of exercise, (2) self-administered the study drug no more than 10 minutes prior to exercise (5 minutes was the target), (3) conducted a protocol allowed exercise for moderate to high intensity for at least 30 minutes and no longer than 75 minutes, and (4) achieved a target heart rate of 80% of maximum calculated heart rate at least once during the session. Exercise sessions were expected to occur at least 2 to 3 times per week. Only 1 qualified exercise session per subject per day was included in the analysis (the first if >1).
6 secondary outcomes
CRC Phase: Interstitial Glucose Below Target Range
Time frame: Visit 3 (Day 1) and Visit 4 (Day 3 or any day up to Day 29); Assessed continuously 0-300 minutes following the start of the exercise session corresponding to each of the treatments during the corresponding in-clinic visit during the CRC Phase.
Outpatient Phase: Interstitial Glucose Levels Below Target Range
Time frame: Visit 3 (Day 1) and Visit 4 (Day 3 or any day up to Day 29); Assessed continuously 0-300 minutes following the start of each qualified exercise session corresponding to each of the treatments during the Outpatient Phase.
Outpatient Phase: Insulin Use Change From Baseline
Time frame: Insulin use measured continuously from Study Baseline to End of Study and assessed during Outpatient Phase as Change from Outpatient Phase Baseline at Study Weeks 4, 8, and 12
Outpatient Phase: Barriers to Physical Activity Diabetes (Type 1): BAPAD-1 Change From Baseline
Time frame: Baseline to End of Study measured at Outpatient Phase Baseline (Visit 3, Day 1) and Follow-up (Visit 11, 14-21 days after last exercise session, up to Day 134) or Early Termination (at time of discontinuation)
Outpatient Phase: HFS-II Overall Score Change From Baseline
Time frame: Baseline to End of Study measured at Outpatient Phase Baseline (Visit 3, Day 1) and Follow-up (Visit 11, 14-21 days after last exercise session, up to Day 134) or Early Termination (at time of discontinuation)
Outpatient Phase: Hypoglycemic Confidence Scale (HCS) Change From Baseline
Time frame: Baseline to End of Study measured at Outpatient Phase Baseline (Visit 3, Day 1) and Follow-up (Visit 11, 14-21 days after last exercise session, up to Day 134) or Early Termination (at time of discontinuation)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 36689626Aronson R, Riddell MC, Conoscenti V, Junaidi MK. Effect of Mini-Dose Ready-to-Use Liquid Glucagon on Preventing Exercise-Associated Hypoglycemia in Adults With Type 1 Diabetes. Diabetes Care. 2023 Apr 1;46(4):765-772. doi: 10.2337/dc22-1145.
- 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.
Khaled Junaidi, MD study chair
Xeris Pharmaceuticals
1 site 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 RTU Injection With Insulin Pump Reduction and Glugaon RTU Injection Without Insulin Pump Reduction in people with Hypoglycemia, run by Xeris Pharmaceuticals at 1 site in Canada.
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 10 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 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in 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. 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 25 Aug 2023). 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?
Outpatient Phase: Incidence Rate of Hypoglycemia During and After Moderate to High Intensity Aerobic Exercise. (time frame: Daily; During the 12-week Outpatient Phase qualified exercise sessions were assessed daily and associated hypoglycemia events were assessed continuously during and within the 30 (+2) minute period following a qualified exercise session.). 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 NCT03841526, 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 Aug 2025.