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Completed

NCT Number: NCT03378635

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

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®.

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Key information

Conditions

Hypoglycemia Autoimmune Diseases Diabetes Mellitus Diabetes Mellitus, Type 1 Endocrine System Diseases Glucose Metabolism Disorders Immune System Diseases Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Clinical Research Center, Medizinische Universität Graz, Graz, Austria

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Dasiglucagon

Drug

Glucagon analog

Other names: ZP4207

GlucaGen

Drug

Native glucagon

Other names: GlucaGen HypoKit

Placebo

Drug

Placebo for dasiglucagon

Other names: Placebo for dasiglucagon

Primary outcomes

  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 outcomes

  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

Sponsors and collaborators

Lead sponsor

Zealand Pharma

Industry

Registry information

Official study 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

Important dates

Study start
2017
Primary completion
2018
Study completion
2018
First posted
Dec 20, 2017
Registry last updated
Jun 10, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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