Trial to Confirm the Clinical Efficacy and Safety of Dasiglucagon in the Treatment of Hypoglycemia in Subjects With T1DM

A Randomized, Double-blind, Parallel-group Trial to Confirm the Clinical Efficacy and Safety of Dasiglucagon in the Rescue Treatment of Hypoglycemia in Subjects With Type 1 Diabetes Mellitus (T1DM) Compared to Placebo

A randomized, double-blind, parallel-group trial to confirm the clinical efficacy and safety of dasiglucagon in the rescue treatment of hypoglycemia in subjects with type 1 diabetes mellitus (T1DM) compared to placebo

Study Overview

• Status: Completed
• Conditions: Hypoglycemia; Diabetes Mellitus, Type 1
• Intervention / Treatment: Drug: Dasiglucagon; Drug: Placebo

Detailed Description

Subjects were randomized in a ratio of 3:1 to receive a single subcutaneous dose of dasiglucagon (0.6 mg) or matching placebo. Randomization also determined whether the subject was to be injected in the buttock or deltoid. During the dosing visit (Visit 2), hypoglycemia was induced by a fast-acting insulin glulisine (Apidra®) infusion, and trial drug was administered when the subject's plasma glucose level was 45-60 mg/dL (2.5-3.3 mmol/L). During the insulin-induced hypoglycemia, pharmacokinetic and pharmacodynamic samples were drawn, and plasma glucose levels were monitored closely at site for safety reasons. A rescue glucose infusion could be administered to ameliorate persistent hypoglycemia. Subjects were followed for at least 28 days after dosing to perform an adequate immunogenicity evaluation of treatment.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Chula Vista, California, United States, 91911
      • ProSciento, Inc.
    • Escondido, California, United States, 92025
      • AMCR Institute
  • Washington
    • Renton, Washington, United States, 98057
      • Rainier Clinical Research, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Female or male subjects with T1DM for at least 1 year; diagnostic criteria as defined by the American Diabetes Association (3).
• 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%.
• Aged between 18 and 75 years, both inclusive.

Exclusion Criteria:

• Previous participation in a clinical trial within the dasiglucagon in the rescue treatment of hypoglycemia program.
• Known or suspected allergy to trial drug(s) or related products.
• History of anaphylaxis or symptoms of severe systemic allergy (such as angioedema).
• Previous participation in this trial. Participation being defined by signing the informed consent document.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dasiglucagon; single fixed dose (subcutaneous injection) of dasiglucagon	Drug: Dasiglucagon; Glucagon analogue; Other Names: ZP4207
Placebo Comparator: Placebo; single fixed dose (subcutaneous injection) of placebo	Drug: Placebo; Placebo for dasiglucagon; Other Names: Placebo for dasiglucagon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Plasma Glucose Recovery.	Plasma glucose recovery was 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 intravenous (IV) glucose. Patients who received rescue IV glucose before 45 minutes and patients not recovering within 45 minutes after dosing were censored at 45 minutes.	0-45 minutes after dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Glucose Recovery After Trial Drug Injection	Plasma glucose recovery (patient has achieved increase in plasma glucose of ≥20 mg/dL (1.1 mmol/L)) within 30 minutes, within 20 minutes, within 15 minutes, and within 10 minutes after trial drug injection without administration of rescue intravenous (IV) glucose.	0-30 minutes after dosing
Plasma Glucose Changes From Baseline	Plasma glucose changes from baseline at 30 minutes, at 20 minutes, at 15 minutes, and at 10 minutes after trial drug injection or at the time of rescue (patient level).	0-30 minutes after dosing
Time to Target Plasma Glucose Concentration	Time to first plasma glucose concentration ≥70 mg/dL (3.9 mmol/L) without administration of rescue intravenous glucose	0-45 minutes after dosing
Pharmacodynamics - Area Under the Effect Curve	Plasma glucose response as area under the effect curve (AUE) above baseline from time zero to 30 minutes, AUE0-30min.	0-30 minutes after dosing
Pharmacokinetics - Area Under the Plasma Concentration Curve	Area under the drug concentration curve (AUC) from time zero to 90 minutes, AUC0-90min	0-90 minutes after dosing
Pharmacokinetics - Area Under the Plasma Concentration Curve	Area under the drug concentration curve (AUC) from time zero to 120 minutes, AUC0-120min	0-120 minutes after dosing
Pharmacokinetics - Maximum Plasma Concentration	Maximum plasma dasiglucagon concentration (Cmax)	0-120 minutes after dosing
Pharmacokinetics - Time to Maximum Plasma Concentration	Time to maximum plasma dasiglucagon concentration (tmax)	0-120 minutes after dosing
Immunogenicity - Occurrence of Anti-drug Antibodies	Occurrence of antibodies against dasiglucagon. Presented as percentage of patients with antibodies.	58 days
Rescue Infusions of IV Glucose After Trial Drug Administration	Presented as number of patients with rescue infusions of IV glucose after trial drug administration. This was a safety outcome measure. IV = intravenous	0-45 minutes after dosing
Time to First Rescue Infusion of IV Glucose After Trial Drug Administration	Safety outcome measure: time to first rescue infusion of IV glucose after trial drug administration. IV = intravenous	0-45 minutes after dosing

Collaborators and Investigators

• Sponsor: Zealand Pharma

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2018
• Primary Completion (Actual): March 11, 2019
• Study Completion (Actual): March 11, 2019

Study Registration Dates

• First Submitted: September 25, 2018
• First Submitted That Met QC Criteria: September 27, 2018
• First Posted (Actual): September 28, 2018

Study Record Updates

• Last Update Posted (Actual): May 19, 2021
• Last Update Submitted That Met QC Criteria: April 28, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: glucagon
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemia
• Other Study ID Numbers: ZP4207-17145

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No