search
Back to results

A Trial to Confirm the Efficacy and Safety of Dasiglucagon in the Treatment of Hypoglycemia in Type 1 Diabetes Subjects

Primary Purpose

Hypoglycemia, Diabetes Mellitus, Type 1

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Dasiglucagon
GlucaGen
Placebo
Sponsored by
Zealand Pharma
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypoglycemia focused on measuring Dasiglucagon, Glucagon analog

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Female or male subjects with type 1 diabetes mellitus (T1DM) for at least 1 year, diagnostic criteria as defined by the American Diabetes Association
  • Treated with insulin for T1DM for at least 1 year and with stable insulin treatment (defined as no more than a 10-unit daily variation in total daily insulin dose) 30 days prior to screening
  • Hemoglobin A1c <10%

Exclusion Criteria:

  • Previously treated with dasiglucagon (previously referred to as ZP4207)
  • Known or suspected allergy to trial product(s) or related products
  • Females who are pregnant according to a positive pregnancy test, are actively attempting to get pregnant, or are lactating.
  • History of hypoglycemic events associated with seizures in the last year prior to screening
  • History of severe hypoglycemia in the last month prior to screening
  • Active malignancy within the last 5 years
  • Current bleeding disorder, including anti-coagulant treatment
  • Known presence or history of pheochromocytoma (i.e. adrenal gland tumor) or insulinoma (i.e. insulin secreting pancreas tumor)
  • Use of a daily systemic beta-blocker drug, indomethacin, warfarin or anticholinergic drugs in the previous 28 days before Day 1 of this trial
  • Clinically significant abnormal ECG at screening as judged by the investigator
  • Donation of blood or plasma in the past month, or in excess of 500 mL within 12 weeks prior to screening
  • Surgery or trauma with significant blood loss within the last 2 months prior to screening
  • A positive result in the alcohol and/or urine drug screen at the screening visit. Significant history of alcoholism or drug abuse as judged by the investigator or consuming more than 24 g alcohol per day for men, or more than 12 g alcohol per day for women

Sites / Locations

  • ProSciento
  • Clinical Research Center, Medizinische Universität Graz
  • LMC Diabetes & Manna Research
  • Profil
  • Profil

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Active Comparator

Arm Label

Dasiglucagon

Placebo

GlucaGen®

Arm Description

Single fixed dose (s.c.injection) of dasiglucagon

Single fixed dose (s.c.injection) of placebo

Single fixed dose (s.c.injection) of GlucaGen®

Outcomes

Primary Outcome Measures

Time to Plasma Glucose Recovery
Plasma glucose recovery is defined as first increase in plasma glucose of ≥20 mg/dL (1.1 mmol/L) from baseline without administration of rescue intravenous glucose. The outcome measure used a Kaplan-Meier estimate with 95% confidence interval. Treatment groups without censoring utilized a distribution free method to compute the confidence interval for median time.

Secondary Outcome Measures

Plasma Glucose Recovery
Plasma glucose recovery within 30 minutes, within 20 minutes, within 15 minutes, and within 10 minutes after study drug injection without administration of rescue IV glucose. Plasma glucose recovery was defined as the first increase in plasma glucose of ≥20 mg/dL (1.1 mmol/L) from baseline without administration of rescue intravenous glucose.
Plasma Glucose Changes From Baseline
Plasma glucose changes from baseline at 30 minutes, 20 minutes, 15 minutes and 10 minutes after study drug injection without administration of rescue intravenous glucose
Time to Target
Time to first plasma glucose concentration ≥70 mg/dL (3.9 mmol/L) without administration of rescue intravenous glucose. The outcome measure used a Kaplan-Meier estimate with 95% confidence interval. Treatment groups without censoring utilized a distribution free method to compute the confidence interval for median time.
Pharmacodynamics - Area Under the Effect Curve
Plasma glucose response as area under the effect curve (AUE) above baseline from time zero to 30 minutes. Samples were collected pre-dose, and at 4, 6, 8, 10, 12, 15, 17, 20, 25 and 30 minutes after dosing.
Pharmacokinetics - Area Under the Plasma Concentration Curve
Area under the drug concentration curve from time zero to 90 minutes, AUC0-90min. To calculate the AUC the standard trapezoidal method was used, based on actual rather than nominal time points. Samples were collected pre-dose, and at 15, 30, 35, 40, 50, 60, 90 and 120 minutes after dosing.
Pharmacokinetics - Area Under the Plasma Concentration Curve
Area under the drug concentration curve from time zero to 120 minutes, AUC0-120min. To calculate the AUC the standard trapezoidal method was used, based on actual rather than nominal time points. Samples were collected pre-dose, and at 15, 30, 35, 40, 50, 60, 90 and 120 minutes after dosing.
Pharmacokinetics - Maximum Plasma Concentration
Maximum plasma drug concentration (Cmax). Maximum plasma drug concentration was determined as the maximum of all valid plasma dasiglucagon/glucagon concentrations. Samples were collected pre-dose, and at 15, 30, 35, 40, 50, 60, 90 and 120 minutes after dosing.
Pharmacokinetics - Time to Maximum Plasma Concentration
Time to maximum plasma drug concentration (tmax). Median Tmax was determined as the time point where the maximum of all valid plasma dasiglucagon/glucagon concentration measurements for each measurement series was observed. Samples were collected pre-dose, and at 15, 30, 35, 40, 50, 60, 90 and 120 minutes after dosing.
Immunogenicity - Occurence of Anti-drug Antibodies
Occurence of antibodies against dasiglucagon/GlucaGen
Rescue Infusion of IV Glucose During the Hypoglycemic Clamp Procedure
Number of patients receiving administration of rescue infusion of IV glucose during the hypoglycemic clamp procedure. IV = intravenous
Time to First Rescue Infusion of IV Glucose
Time to first rescue administration of rescue infusion of IV glucose. IV = intravenous

Full Information

First Posted
December 8, 2017
Last Updated
May 27, 2021
Sponsor
Zealand Pharma
search

1. Study Identification

Unique Protocol Identification Number
NCT03378635
Brief Title
A Trial to Confirm the Efficacy and Safety of Dasiglucagon in the Treatment of Hypoglycemia in Type 1 Diabetes Subjects
Official Title
A Phase 3, Randomized, Double-blind, Parallel Trial to Confirm the Clinical Efficacy and Safety of Dasiglucagon in Rescue Treatment of Hypoglycemia in Subjects With Type 1 Diabetes Mellitus Compared to Placebo and With Reference to GlucaGen
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
December 7, 2017 (Actual)
Primary Completion Date
April 27, 2018 (Actual)
Study Completion Date
May 25, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Zealand Pharma

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
The objective of the trial is to demonstrate superiority of dasiglucagon compared to placebo following a single subcutaneous dose administered to subjects with type 1 diabetes mellitus (T1DM) with insulin-induced hypoglycemia. Additionally to compare the glycemic response observed after administration dasiglucagon with that of GlucaGen®.
Detailed Description
This was a global, multicenter, randomized, parallel, and double-blind clinical trial confirming the efficacy and safety of dasiglucagon for insulin-induced hypoglycemia in patients with T1DM. The patients were randomized 2:1:1 to receive a single subcutaneous 0.6 mg dose of dasiglucagon, placebo, or a 1 mg dose of GlucaGen and followed for at least 28 days after receiving treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypoglycemia, Diabetes Mellitus, Type 1
Keywords
Dasiglucagon, Glucagon analog

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
170 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dasiglucagon
Arm Type
Experimental
Arm Description
Single fixed dose (s.c.injection) of dasiglucagon
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Single fixed dose (s.c.injection) of placebo
Arm Title
GlucaGen®
Arm Type
Active Comparator
Arm Description
Single fixed dose (s.c.injection) of GlucaGen®
Intervention Type
Drug
Intervention Name(s)
Dasiglucagon
Other Intervention Name(s)
ZP4207
Intervention Description
Glucagon analog
Intervention Type
Drug
Intervention Name(s)
GlucaGen
Other Intervention Name(s)
GlucaGen HypoKit
Intervention Description
Native glucagon
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo for dasiglucagon
Intervention Description
Placebo for dasiglucagon
Primary Outcome Measure Information:
Title
Time to Plasma Glucose Recovery
Description
Plasma glucose recovery is defined as first increase in plasma glucose of ≥20 mg/dL (1.1 mmol/L) from baseline without administration of rescue intravenous glucose. The outcome measure used a Kaplan-Meier estimate with 95% confidence interval. Treatment groups without censoring utilized a distribution free method to compute the confidence interval for median time.
Time Frame
0-45 minutes after dosing
Secondary Outcome Measure Information:
Title
Plasma Glucose Recovery
Description
Plasma glucose recovery within 30 minutes, within 20 minutes, within 15 minutes, and within 10 minutes after study drug injection without administration of rescue IV glucose. Plasma glucose recovery was defined as the first increase in plasma glucose of ≥20 mg/dL (1.1 mmol/L) from baseline without administration of rescue intravenous glucose.
Time Frame
0-30 minutes after dosing: assessed at 10, 15, 20 and 30 minutes after study drug injection
Title
Plasma Glucose Changes From Baseline
Description
Plasma glucose changes from baseline at 30 minutes, 20 minutes, 15 minutes and 10 minutes after study drug injection without administration of rescue intravenous glucose
Time Frame
0-30 minutes after dosing: assessed at 10, 15, 20 and 30 minutes after study drug injection
Title
Time to Target
Description
Time to first plasma glucose concentration ≥70 mg/dL (3.9 mmol/L) without administration of rescue intravenous glucose. The outcome measure used a Kaplan-Meier estimate with 95% confidence interval. Treatment groups without censoring utilized a distribution free method to compute the confidence interval for median time.
Time Frame
0-45 minutes after dosing
Title
Pharmacodynamics - Area Under the Effect Curve
Description
Plasma glucose response as area under the effect curve (AUE) above baseline from time zero to 30 minutes. Samples were collected pre-dose, and at 4, 6, 8, 10, 12, 15, 17, 20, 25 and 30 minutes after dosing.
Time Frame
0-30 minutes after dosing
Title
Pharmacokinetics - Area Under the Plasma Concentration Curve
Description
Area under the drug concentration curve from time zero to 90 minutes, AUC0-90min. To calculate the AUC the standard trapezoidal method was used, based on actual rather than nominal time points. Samples were collected pre-dose, and at 15, 30, 35, 40, 50, 60, 90 and 120 minutes after dosing.
Time Frame
0-90 minutes after dosing
Title
Pharmacokinetics - Area Under the Plasma Concentration Curve
Description
Area under the drug concentration curve from time zero to 120 minutes, AUC0-120min. To calculate the AUC the standard trapezoidal method was used, based on actual rather than nominal time points. Samples were collected pre-dose, and at 15, 30, 35, 40, 50, 60, 90 and 120 minutes after dosing.
Time Frame
0-120 minutes after dosing
Title
Pharmacokinetics - Maximum Plasma Concentration
Description
Maximum plasma drug concentration (Cmax). Maximum plasma drug concentration was determined as the maximum of all valid plasma dasiglucagon/glucagon concentrations. Samples were collected pre-dose, and at 15, 30, 35, 40, 50, 60, 90 and 120 minutes after dosing.
Time Frame
0-120 minutes after dosing
Title
Pharmacokinetics - Time to Maximum Plasma Concentration
Description
Time to maximum plasma drug concentration (tmax). Median Tmax was determined as the time point where the maximum of all valid plasma dasiglucagon/glucagon concentration measurements for each measurement series was observed. Samples were collected pre-dose, and at 15, 30, 35, 40, 50, 60, 90 and 120 minutes after dosing.
Time Frame
0-120 minutes after dosing
Title
Immunogenicity - Occurence of Anti-drug Antibodies
Description
Occurence of antibodies against dasiglucagon/GlucaGen
Time Frame
28 days
Title
Rescue Infusion of IV Glucose During the Hypoglycemic Clamp Procedure
Description
Number of patients receiving administration of rescue infusion of IV glucose during the hypoglycemic clamp procedure. IV = intravenous
Time Frame
0-45 minutes after dosing
Title
Time to First Rescue Infusion of IV Glucose
Description
Time to first rescue administration of rescue infusion of IV glucose. IV = intravenous
Time Frame
0-45 minutes after dosing

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Female or male subjects with type 1 diabetes mellitus (T1DM) for at least 1 year, diagnostic criteria as defined by the American Diabetes Association Treated with insulin for T1DM for at least 1 year and with stable insulin treatment (defined as no more than a 10-unit daily variation in total daily insulin dose) 30 days prior to screening Hemoglobin A1c <10% Exclusion Criteria: Previously treated with dasiglucagon (previously referred to as ZP4207) Known or suspected allergy to trial product(s) or related products Females who are pregnant according to a positive pregnancy test, are actively attempting to get pregnant, or are lactating. History of hypoglycemic events associated with seizures in the last year prior to screening History of severe hypoglycemia in the last month prior to screening Active malignancy within the last 5 years Current bleeding disorder, including anti-coagulant treatment Known presence or history of pheochromocytoma (i.e. adrenal gland tumor) or insulinoma (i.e. insulin secreting pancreas tumor) Use of a daily systemic beta-blocker drug, indomethacin, warfarin or anticholinergic drugs in the previous 28 days before Day 1 of this trial Clinically significant abnormal ECG at screening as judged by the investigator Donation of blood or plasma in the past month, or in excess of 500 mL within 12 weeks prior to screening Surgery or trauma with significant blood loss within the last 2 months prior to screening A positive result in the alcohol and/or urine drug screen at the screening visit. Significant history of alcoholism or drug abuse as judged by the investigator or consuming more than 24 g alcohol per day for men, or more than 12 g alcohol per day for women
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christina Sylvest, MSc Pharm
Organizational Affiliation
Zealand Pharma
Official's Role
Study Director
Facility Information:
Facility Name
ProSciento
City
Chula Vista
State/Province
California
ZIP/Postal Code
91911
Country
United States
Facility Name
Clinical Research Center, Medizinische Universität Graz
City
Graz
Country
Austria
Facility Name
LMC Diabetes & Manna Research
City
Toronto
Country
Canada
Facility Name
Profil
City
Mainz
Country
Germany
Facility Name
Profil
City
Neuss
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35239971
Citation
Pieber TR, Aronson R, Hovelmann U, Willard J, Plum-Morschel L, Knudsen KM, Bandak B, Tehranchi R. Dasiglucagon-A Next-Generation Glucagon Analog for Rapid and Effective Treatment of Severe Hypoglycemia: Results of Phase 3 Randomized Double-Blind Clinical Trial. Diabetes Care. 2021 Jun 1;44(6):1361-1367. doi: 10.2337/dc20-2995.
Results Reference
derived

Learn more about this trial

A Trial to Confirm the Efficacy and Safety of Dasiglucagon in the Treatment of Hypoglycemia in Type 1 Diabetes Subjects

We'll reach out to this number within 24 hrs