Glucagon Ready-to-Use (RTU) for Prevention of Exercise-Induced Hypoglycemia During Aerobic Exercise in Adults With T1D

NCT03841526 | Completed Phase 2 Results FDA Drug

• 1 other identifier: XSMP-204
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Hypoglycemia

Keywords

Exercise; Glucagon; Insulin

Outcome Measures

Primary Outcomes (3)

• 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.

  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).

  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).

  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

  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

  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 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

  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

  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)

Other Outcomes (3)

• CRC Phase: Incidence Rate of Hypoglycemia During and After Moderate to High Intensity Aerobic Exercise Exercise.

  Visit 3 (Day 1) and Visit 4 (Day 3 or any day up to Day 29); At each visit, the associated hypoglycemia events were assessed continuously throughout the 30 (+2) minute period following a qualified exercise session.

• CRC Phase: Mean Number of Hypoglycemic Events Exercise.

  Visit 3 (Day 1) and Visit 4 (Day 3 or any day up to Day 29); At each visit, the associated hypoglycemia events were assessed continuously throughout the 30 (+2) minute period following a qualified exercise session.

• CRC Phase: Mean Number of Qualified High Intensity Aerobic Exercise Sessions

  Visit 3 (Day 1) and Visit 4 (Day 3 or any day up to Day 29); At each visit, the number of qualified exercise sessions that occurred.

Study Arms (5)

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

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

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)

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)

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)

Drug: Glugaon RTU Injection Without Insulin Pump Reduction

Interventions

Glucagon RTU Injection With Insulin Pump Reduction DRUG

0.15 mg injection with 50% pump reduction

Also known as: XP-3994

CRC Phase: Glucagon RTU With Insulin Pump Reduction; Outpatient Phase: Glucagon RTU With Insulin Pump Reduction

Vehicle for Glucagon RTU Injection With Insulin Pump Reduction OTHER

vehicle injection with 50% pump reduction

Also known as: Placebo

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 Reduction DRUG

0.15 mg injection without pump reduction

Also known as: XP-3994

Outpatient Phase: Glucagon RTU Without Insulin Pump Reduction

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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)).
• 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.

Sponsors & Collaborators

• Xeris Pharmaceuticals: lead

Study Sites (1)

LMC Clinical Research Inc

Toronto, Ontario, M4G 3E8, Canada

Location

Related Publications (1)

• 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.

  PMID: 36689626 RESULT

MeSH Terms

Conditions

Hypoglycemia; Motor Activity; Insulin Resistance

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Behavior; Hyperinsulinism

Results Point of Contact

• Title: Dawn Harper, VP Clinical Devlopment
• Organization: Xeris Pharmaceuticals

clinicaltrials@xerispharma.com

1-877-XERIS-37

Study Officials

• Khaled Junaidi, MD

  Xeris Pharmaceuticals

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: CRC Phase was a fully masked double-blind crossover with each subject receiving each treatment 1 time. In the Outpatient Phase, the two arms with 50% insulin pump reduction were double-blind (fully masked) and the arm with Glucagon RTU and no insulin pump reduction was open-label.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 12, 2019
• First Posted: February 15, 2019
• Study Start: August 22, 2019
• Primary Completion: April 2, 2020
• Study Completion: April 2, 2020
• Last Updated: August 22, 2025
• Results First Posted: August 25, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)