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CompletedNCT03738865Updated May 22, 2020Results posted

G-Pen Compared to Glucagen Hypokit for Severe Hypoglycemia Rescue in Adults With Type 1 Diabetes

A Phase 3 interventional study of G-Pen and Novo Glucagon in Insulin Hypoglycemia, Type 1 Diabetes Mellitus and Severe Hypoglycemia, sponsored by Xeris Pharmaceuticals. Completed at 7 sites in 3 countries. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2020-05-22.

Sponsored by Xeris Pharmaceuticals · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
132
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study summary

This is a multi-center, randomized, controlled, single-blind, two-way crossover efficacy and safety study in subjects with Type 1 diabetes mellitus. The study involves two daytime clinical research center (CRC) visits with random assignment to receive G-Pen glucagon 1 mg during one period and Novo Glucagon 1 mg during the other. Each daytime visit is preceded by an overnight stay in the CRC. In the morning of the inpatient study visit, the subject is brought into a state of severe hypoglycemia through IV administration of regular insulin diluted in normal saline. After a hypoglycemic state with plasma glucose \< 54 mg/dL (3 mmol/L) is verified, the subject is administered a dose of G-Pen or Novo Glucagon via subcutaneous injection. Plasma glucose levels are monitored for up to 180 minutes post-dosing, with a value of >70.0 mg/dL (3.89 mmol/L) or an increase of > 20 mg/dL (>1.11 mmol/L) within 30 minutes of glucagon administration indicating a positive response. After 3 hours, the subject is given a meal and discharged when medically stable. After a wash-out period of 7 to 28 days, subjects return to the CRC, and the procedures are repeated with each subject crossed over to the other treatment. A follow-up visit as a safety check is conducted 2-7 days following administration of the final dose of study drug.

02

Conditions studied

  • Insulin Hypoglycemia
  • Type 1 Diabetes Mellitus
  • Severe Hypoglycemia

Keywords

  • glucagon
  • hypoglycemia
03

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Males and non-pregnant females diagnosed with type 1 diabetes (T1D) for at least 24 months.
  2. Current usage of daily insulin treatment that includes having an assigned "correction factor" for managing hyperglycemia.
  3. Age 18 to 75 years, inclusive.
  4. Random serum C-peptide concentration \< 0.6 ng/mL.
  5. Willingness to follow all study procedures, including attending all clinic visits.
  6. Subject has provided informed consent as evidenced by a signed and dated informed consent form (ICF) completed before any trial-related activities occur.

Exclusion criteria

Exclusion Criteria:

  1. Pregnancy
  2. Glycated hemoglobin (HbA1c) > 10% at Screening.
  3. Body mass index (BMI) > 40 kg/m2.
  4. Renal insufficiency (serum creatinine greater than 3.0 mg/dL) or end-stage renal disease requiring renal replacement therapy.
  5. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) equal to or greater than 3 times the upper limit of normal.
  6. Hepatic synthetic insufficiency as defined as a serum albumin of less than 3.0 g/dL.
  7. Hematocrit \< 30%.
  8. Blood pressure (BP) readings at Screening where systolic blood pressure (SBP) \< 90 or > 150 mm Hg, and diastolic blood pressure (DBP) \< 50 or > 100 mm Hg.
  9. Clinically significant electrocardiogram (ECG) abnormalities.
  10. Use of total insulin dose per day > 2 U/kg.
  11. Inadequate venous access.
  12. Congestive heart failure, New York Heart Association (NYHA) class III or IV.
  13. History of myocardial infarction, unstable angina, or revascularization within the past 6 months.
  14. History of a cerebrovascular accident in the past 6 months or with major neurological deficits.
  15. Active malignancy within 5 years from Screening, except basal cell or squamous cell skin cancers. Any history of breast cancer or malignant melanoma will be exclusionary.
  16. Major surgical operation within 30 days prior to Screening.
  17. Current seizure disorder (other than with suspect or documented hypoglycemia).
  18. Current bleeding disorder, treatment with warfarin, or platelet count below 50 × 109 per liter.
  19. History of pheochromocytoma or disorder with increased risk of pheochromocytoma (multiple endocrine neoplasia type 2 (MEN 2), neurofibromatosis, or Von Hippel-Lindau disease).
  20. History of insulinoma.
  21. History of allergies to glucagon or glucagon-like products, or any history of significant hypersensitivity to glucagon or any related products or to any of the excipients (DMSO and trehalose) in the investigational formulation.
  22. History of glycogen storage disease.
  23. Subject tests positive for human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) infection (hepatitis B surface antigen positive [HBsAg+]) at Screening.
  24. Active substance other than tetrahydrocannabinol (THC) or alcohol abuse (more than 21 drinks per week for male subjects or 14 drinks per week for female subject).
  25. Administration of glucagon within 7 days of Screening.
  26. 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.
  27. Any other reason the Investigator deems exclusionary.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Single (Participant)
Enrollment
132 participants (actual)

Study arms

  • Experimental
    G-Pen followed by Novo Glucagon

    1 mg G-Pen at the first treatment visit followed by 1 mg Novo Glucagon at the second treatment visit

    Drug: G-Pen · Drug: Novo Glucagon

  • Active comparator
    Novo Glucagon followed by G-Pen

    1 mg Novo Glucagon at the first treatment visit followed by 1 mg G-Pen at the second treatment visit

    Drug: G-Pen · Drug: Novo Glucagon

Interventions

  • DrugG-Pen

    1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector

    Also known as: glucagon

  • DrugNovo Glucagon

    1 mg subcutaneous injection of Novo Glucagon (glucagon injection)

    Also known as: Glucagen Hypokit

05

What researchers measure

Primary outcomes

  1. Severe Hypoglycemia Rescue

    Number of subjects with an increase in plasma glucose concentration from below 54 mg/dL (3 mmol/L) to greater than 70 mg/dL (3.89 mmol/L) or an increase in plasma glucose concentration \> 20 mg/dL (\> 1.11 mmol/L) within 30 minutes after administration of glucagon

    Time frame: At 30 minutes following administration of study drug

Secondary outcomes

  1. Plasma Glucose Response 1

    Number of subjects with an increase in plasma glucose concentration from below 54 mg/dL (3 mmol/L) to greater than 70 mg/dL (3.89 mmol/L) within 30 minutes of a decision to dose

    Time frame: At 30 minutes following a decision to administer study drug

  2. Plasma Glucose Response 2

    Number of subjects with an increase in plasma glucose concentration \> 20 mg/dL (\> 1.11 mmol/L) after administration of glucagon.

    Time frame: At 0-30 minutes following a decision to administer study drug

  3. Administration Time

    Mean time (minutes) to administer study drug from a decision to dose

    Time frame: At 0-10 minutes from a decision to administer study drug

  4. Hypoglycemia Resolution

    Mean time (minutes) to complete resolution of the overall sensation of hypoglycemia from a decision to dose

    Time frame: At 0-90 minutes following administration of study drug

06

Results

Posted May 13, 2020

Participant flow

Participant flow — Overall Study
MilestoneG-Pen, Then Novo GlucagonNovo Glucagon, Then G-Pen
Started6666
Completed6162
Not completed54
Withdrew: Withdrawal by subject33
Withdrew: Adverse event20
Withdrew: Physician decision01

Outcome measures

PrimarySevere Hypoglycemia Rescue

Number of subjects with an increase in plasma glucose concentration from below 54 mg/dL (3 mmol/L) to greater than 70 mg/dL (3.89 mmol/L) or an increase in plasma glucose concentration \> 20 mg/dL (\> 1.11 mmol/L) within 30 minutes after administration of glucagon

Time frame:
At 30 minutes following administration of study drug
Reported as:
Count of participants · Participants
Severe Hypoglycemia Rescue
ParticipantsG-PenNovo Glucagon
Severe Hypoglycemia Rescue127123
SecondaryPlasma Glucose Response 1

Number of subjects with an increase in plasma glucose concentration from below 54 mg/dL (3 mmol/L) to greater than 70 mg/dL (3.89 mmol/L) within 30 minutes of a decision to dose

Time frame:
At 30 minutes following a decision to administer study drug
Reported as:
Count of participants · Participants
Plasma Glucose Response 1
ParticipantsG-PenNovo Glucagon
Plasma Glucose Response 1127123
SecondaryPlasma Glucose Response 2

Number of subjects with an increase in plasma glucose concentration \> 20 mg/dL (\> 1.11 mmol/L) after administration of glucagon.

Time frame:
At 0-30 minutes following a decision to administer study drug
Reported as:
Count of participants · Participants
Plasma Glucose Response 2
ParticipantsG-PenNovo Glucagon
Plasma Glucose Response 2127123
SecondaryAdministration Time

Mean time (minutes) to administer study drug from a decision to dose

Time frame:
At 0-10 minutes from a decision to administer study drug
Reported as:
Mean · minutes
Administration Time
minutesG-PenNovo Glucagon
Administration Time0.79 ± 0.5301.76 ± 0.678
SecondaryHypoglycemia Resolution

Mean time (minutes) to complete resolution of the overall sensation of hypoglycemia from a decision to dose

Time frame:
At 0-90 minutes following administration of study drug
Reported as:
Mean · minutes
Hypoglycemia Resolution
minutesG-PenNovo Glucagon
Hypoglycemia Resolution15.69 ± 7.42815.32 ± 8.479

Adverse events

Collected over Adverse events were collected for up to 5 weeks, from the time of consent through the follow-up visit.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
G-Pen0/127 (0%)0/127 (0%)67/127 (52.8%)
Novo Glucagon0/123 (0%)0/123 (0%)57/123 (46.3%)
Most frequent other events
Most frequent other events
EventG-PenNovo Glucagon
NauseaGastrointestinal disorders54/12755/123
VomitingGastrointestinal disorders16/12717/123
HeadacheNervous system disorders7/1279/123

Baseline characteristics

All Randomized Population

Age, Categorical
Age, Categorical(Participants)G-Pen, Then Novo GlucagonNovo Glucagon, Then G-PenTotal
<=18 years000
Between 18 and 65 years6363126
>=65 years336
Sex: Female, Male
Sex: Female, Male(Participants)G-Pen, Then Novo GlucagonNovo Glucagon, Then G-PenTotal
Female293362
Male373370
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)G-Pen, Then Novo GlucagonNovo Glucagon, Then G-PenTotal
Hispanic or Latino134
Not Hispanic or Latino6563128
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)G-Pen, Then Novo GlucagonNovo Glucagon, Then G-PenTotal
American Indian or Alaska Native000
Asian336
Native Hawaiian or Other Pacific Islander101
Black or African American022
White6261123
More than one race000
Unknown or Not Reported000
07

Study locations

7 sites
  • Diablo Clinical Research
    Walnut Creek, California 94598, United States
  • Atlanta Diabetes Associates
    Atlanta, Georgia 30318, United States
  • PPD-Las Vegas Clinical Research Unit
    Las Vegas, Nevada 89113, United States
  • Rainier Research Center
    Renton, Washington 98057, United States
  • Medizinische Universität Graz-Center for Medical Research
    Graz, 8010, Austria
  • LMC Diabetes & Endocrinology
    Toronto, Ontario M4G 3E8, Canada
  • AltaSciences
    Montréal, Quebec H3P 3P1, Canada
08

References and documents

Publications

  • Pieber TR, Aronson R, Christiansen MP, Bode B, Junaidi K, Conoscenti V. Efficacy, safety, tolerability, and noninferiority phase 3 study of glucagon as a ready-to-use room temperature liquid stable formulation versus a lyophilised formulation for the biochemical recovery and symptomatic relief of insulin-induced severe hypoglycaemia in adults with type 1 diabetes. Diabetes Obes Metab. 2022 Jul;24(7):1394-1397. doi: 10.1111/dom.14699. Epub 2022 Apr 28. No abstract available. PubMed 35322535 ↗

Study documents

  • Study protocol · Dec 17, 2018
  • Statistical analysis plan · Apr 4, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03738865
Lead sponsor
Xeris Pharmaceuticals
Collaborators
Empiristat, Inc.
Responsible party
Sponsor
First posted
Nov 13, 2018
Start date
Sep 27, 2018
Primary completion
Mar 29, 2019
Completion
Apr 2, 2019
Results posted
May 13, 2020
Last update
May 22, 2020

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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