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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

Tracking Information
First Submitted Date  ICMJE December 8, 2017
First Posted Date  ICMJE December 20, 2017
Results First Submitted Date  ICMJE April 13, 2021
Results First Posted Date  ICMJE May 10, 2021
Last Update Posted Date June 10, 2021
Actual Study Start Date  ICMJE December 7, 2017
Actual Primary Completion Date April 27, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 27, 2021)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 13, 2017)
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 during the hypoglycemic clamp procedure without administration of rescue IV glucose.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 27, 2021)
  • 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.
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Immunogenicity - Occurence of Anti-drug Antibodies [ Time Frame: 28 days ]
    Occurence of antibodies against dasiglucagon/GlucaGen
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: December 13, 2017)
  • Plasma glucose recovery [ Time Frame: 0-30 minutes after dosing ]
    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 changes drom baseline [ Time Frame: 0-30 minutes after dosing ]
    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
  • 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 IV glucose
  • Pharmacodynamics - Area under the effect curve [ Time Frame: 0-30 minutes after dosing ]
    Plasma glucose response as area under the curve (AUC) above baseline from time zero to 30 minutes, AUC0-30min.
  • 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
  • Pharmacokinetics - Maximum plasma concentration [ Time Frame: 0-120 minutes after dosing ]
    Maximum plasma drug concentration (Cmax)
  • Pharmacokinetics - Time to maximum plasma concentration [ Time Frame: 0-120 minutes after dosing ]
    Time to maximum plasma drug concentration (tmax)
  • Safety - Adverse events [ Time Frame: 28 days ]
    The incidence, type and severity of adverse events (AEs)
  • Safety - Biochemistry laboratory parameters [ Time Frame: 28 days ]
    Changes from baseline in biochemistry laboratory parameters
  • Safety - Hematology laboratory parameters [ Time Frame: 28 days ]
    Changes from baseline in hematology laboratory parameters
  • Safety - Blood pressure [ Time Frame: 28 days ]
    Changes from baseline in blood pressure (mmHg)
  • Safety - Pulse [ Time Frame: 28 days ]
    Changes from baseline in pulse (beats pr. min)
  • Safety - Physical Examination [ Time Frame: 28 days ]
    Clinically meaningful changes from baseline of the following body systems: head, ears, eyes, nose, throat, including the thyroid gland; heart, lung, chest; abdomen; skin and mucosae; musculoskeletal system; nervous system; lymph node
  • Safety - Electrocardiogram [ Time Frame: 28 days ]
    Clinically meaningful changes from baseline in electrocardiogram (ECG)
  • Safety - Injection site reactions [ Time Frame: 28 days ]
    The incidence, type and severity of injection site reactions
  • Safety - Glucose for rescue [ Time Frame: 0-45 minutes after dosing ]
    Administration of rescue infusion of IV glucose during the hypoglycemic clamp procedure
  • Immunogenicity - Occurence of anti-drug antibodies [ Time Frame: 28 days ]
    Occurence of antibodies against dasiglucagon/GlucaGen
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Trial to Confirm the Efficacy and Safety of Dasiglucagon in the Treatment of Hypoglycemia in Type 1 Diabetes Subjects
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Hypoglycemia
  • Diabetes Mellitus, Type 1
Intervention  ICMJE
  • Drug: Dasiglucagon
    Glucagon analog
    Other Name: ZP4207
  • Drug: GlucaGen
    Native glucagon
    Other Name: GlucaGen HypoKit
  • Drug: Placebo
    Placebo for dasiglucagon
    Other Name: Placebo for dasiglucagon
Study Arms  ICMJE
  • Experimental: Dasiglucagon
    Single fixed dose (s.c.injection) of dasiglucagon
    Intervention: Drug: Dasiglucagon
  • Placebo Comparator: Placebo
    Single fixed dose (s.c.injection) of placebo
    Intervention: Drug: Placebo
  • Active Comparator: GlucaGen®
    Single fixed dose (s.c.injection) of GlucaGen®
    Intervention: Drug: GlucaGen
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 15, 2020)
170
Original Estimated Enrollment  ICMJE
 (submitted: December 13, 2017)
156
Actual Study Completion Date  ICMJE May 25, 2018
Actual Primary Completion Date April 27, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Canada,   Germany,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03378635
Other Study ID Numbers  ICMJE ZP4207-16137
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Zealand Pharma
Study Sponsor  ICMJE Zealand Pharma
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Christina Sylvest, MSc Pharm Zealand Pharma
PRS Account Zealand Pharma
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP