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

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ClinicalTrials.gov Identifier: NCT03378635
Recruitment Status : Completed
First Posted : December 20, 2017
Results First Posted : May 10, 2021
Last Update Posted : June 10, 2021
Sponsor:
Information provided by (Responsible Party):
Zealand Pharma

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®.

Condition or disease Intervention/treatment Phase
Hypoglycemia Diabetes Mellitus, Type 1 Drug: Dasiglucagon Drug: GlucaGen Drug: Placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 170 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : December 7, 2017
Actual Primary Completion Date : April 27, 2018
Actual Study Completion Date : May 25, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Glucagon

Arm Intervention/treatment
Experimental: Dasiglucagon
Single fixed dose (s.c.injection) of dasiglucagon
Drug: Dasiglucagon
Glucagon analog
Other Name: ZP4207

Placebo Comparator: Placebo
Single fixed dose (s.c.injection) of placebo
Drug: Placebo
Placebo for dasiglucagon
Other Name: Placebo for dasiglucagon

Active Comparator: GlucaGen®
Single fixed dose (s.c.injection) of GlucaGen®
Drug: GlucaGen
Native glucagon
Other Name: GlucaGen HypoKit




Primary Outcome Measures :
  1. Time to Plasma Glucose Recovery [ Time Frame: 0-45 minutes after dosing ]
    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 :
  1. Plasma Glucose Recovery [ Time Frame: 0-30 minutes after dosing: assessed at 10, 15, 20 and 30 minutes after study drug injection ]
    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.

  2. Plasma Glucose Changes From Baseline [ Time Frame: 0-30 minutes after dosing: assessed at 10, 15, 20 and 30 minutes after study drug injection ]
    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

  3. Time to Target [ Time Frame: 0-45 minutes after dosing ]
    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.

  4. Pharmacodynamics - Area Under the Effect Curve [ Time Frame: 0-30 minutes after dosing ]
    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.

  5. Pharmacokinetics - Area Under the Plasma Concentration Curve [ Time Frame: 0-90 minutes after dosing ]
    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.

  6. Pharmacokinetics - Area Under the Plasma Concentration Curve [ Time Frame: 0-120 minutes after dosing ]
    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.

  7. Pharmacokinetics - Maximum Plasma Concentration [ Time Frame: 0-120 minutes after dosing ]
    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.

  8. Pharmacokinetics - Time to Maximum Plasma Concentration [ Time Frame: 0-120 minutes after dosing ]
    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.

  9. Immunogenicity - Occurence of Anti-drug Antibodies [ Time Frame: 28 days ]
    Occurence of antibodies against dasiglucagon/GlucaGen

  10. Rescue Infusion of IV Glucose During the Hypoglycemic Clamp Procedure [ Time Frame: 0-45 minutes after dosing ]
    Number of patients receiving administration of rescue infusion of IV glucose during the hypoglycemic clamp procedure. IV = intravenous

  11. Time to First Rescue Infusion of IV Glucose [ Time Frame: 0-45 minutes after dosing ]
    Time to first rescue administration of rescue infusion of IV glucose. IV = intravenous



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03378635


Locations
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United States, California
ProSciento
Chula Vista, California, United States, 91911
Austria
Clinical Research Center, Medizinische Universität Graz
Graz, Austria
Canada
LMC Diabetes & Manna Research
Toronto, Canada
Germany
Profil
Mainz, Germany
Profil
Neuss, Germany
Sponsors and Collaborators
Zealand Pharma
Investigators
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Study Director: Christina Sylvest, MSc Pharm Zealand Pharma
  Study Documents (Full-Text)

Documents provided by Zealand Pharma:
Study Protocol  [PDF] October 8, 2019
Statistical Analysis Plan  [PDF] October 8, 2019

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Responsible Party: Zealand Pharma
ClinicalTrials.gov Identifier: NCT03378635    
Other Study ID Numbers: ZP4207-16137
First Posted: December 20, 2017    Key Record Dates
Results First Posted: May 10, 2021
Last Update Posted: June 10, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Zealand Pharma:
Dasiglucagon
Glucagon analog
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Hypoglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Glucagon
Gastrointestinal Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs