A Trial to Compare the Efficacy and Safety of 2 Different Batches of Subcutaneous Dasiglucagon in Patients With T1DM

A Phase 3b, Randomized, Double-blind, Crossover Trial to Compare the Efficacy and Safety of 2 Different Batches of Subcutaneous Dasiglucagon in Patients With Type 1 Diabetes Mellitus

A randomized, double-blind, crossover trial to compare the efficacy and safety of 2 different batches of subcutaneous dasiglucagon in patients with type 1 diabetes mellitus (T1DM)

Study Overview

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

Detailed Description

This multicenter, double-blind, crossover, randomized clinical trial was designed to evaluate the efficacy and safety of 2 different batches of subcutaneous dasiglucagon in patients with T1DM. Patients were randomly assigned 1:1 to either dasiglucagon Batch A or dasiglucagon Batch B as their initial dose and the other as the second dose. To avoid bias in the evaluation of clinical assessments, the trial was conducted in a double-blinded manner.

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4G 3E8
      • LMC Diabetes & Manna Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Type 1 diabetes mellitus for at least 1 year according to the diagnostic criteria as defined by the American Diabetes Association.
• Hemoglobin A1c <10.0% at screening
• Treated with stable insulin treatment (defined as no more than a 10-unit daily variation in total daily insulin dose) 30 days prior to screening

Exclusion Criteria:

• History of hypoglycemic events associated with seizures in the last year prior to screening
• History of severe hypoglycemia (an episode requiring assistance from another person) in the last month prior to screening
• Previous participation in a clinical trial within the dasiglucagon program

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dasiglucagon batch A crossover to dasiglucagon batch B; V2: Single fixed dose (subcutaneous injection) of dasiglucagon batch A then at V3: Single fixed dose (subcutaneous injection) of dasiglucagon batch B	Drug: dasiglucagon; Glucagon analogue; Other Names: ZP4207
Experimental: Dasiglucagon batch B crossover to dasiglucagon batch A; V2: Single fixed dose (subcutaneous injection) of dasiglucagon batch B then at V3: Single fixed dose (subcutaneous injection) of dasiglucagon batch A	Drug: dasiglucagon; Glucagon analogue; Other Names: ZP4207

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 during the hypoglycemic clamp procedure without administration of rescue intravenous glucose	0-45 minutes after dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Pharmacodynamics - Area under the effect curve 30 min	Area under the baseline-adjusted effect curve (AUE) from zero up to the concentration at 30 minutes, AUE 0-30min	0-30 minutes after dosing
Pharmacodynamics - Area under the effect curve 90 min	Area under the baseline-adjusted effect curve (AUE) from zero up to the concentration at 90 minutes, AUE 0-90min	0-90 minutes after dosing
Pharmacodynamics - Maximum plasma glucose concentration	Change from baseline plasma glucose to maximum plasma glucose measure after dosing, CEmax	0-90 minutes after dosing
Pharmacodynamics - Time maximum plasma glucose concentration	Time to maximum change in plasma glucose measure from baseline, TEmax	0-90 minutes after dosing
Pharmacokinetics - Area under the plasma concentration-time curve 30 min	Area under the concentration-time curve (AUC) from zero up to the concentration at 30 minutes, AUC0-30min	0-30 minutes after dosing
Pharmacokinetics - Area under the plasma concentration-time curve 300 min	Area under the concentration-time curve (AUC) from zero up to the concentration at 300 minutes, AUC0-300min	0-300 minutes after dosing
Pharmacokinetics - Area under the plasma concentration curve Infinitely	Area under the concentration-time curve from zero up to the concentration at infinitely after dosing, AUC0-inf	0-300 minutes after dosing
Pharmacokinetics - Maximum plasma concentration	Measured maximum plasma drug concentration after dosing, Cmax	0-300 minutes after dosing
Pharmacokinetics - Time to maximum plasma concentration	Sampling time until reaching Cmax, Tmax	0-300 minutes after dosing
Pharmacokinetics - Half-life	Half-life dasiglucagon, t½	0-300 minutes after dosing
Pharmacokinetics - Volume of distribution	Apparent volume of distribution of dasiglucagon, Vz/f	0-300 minutes after dosing
Pharmacokinetics - Mean residence time	Mean residence time, MRT	0-300 minutes after dosing
Pharmacokinetics - Body clearance	Total body clearance, CL/f	0-300 minutes after dosing
Safety - Adverse events	The incidence, type and severity of adverse events (AEs)	90 days
Safety - Number of rescue infusions	Number of rescue infusions of IV glucose after trial drug administration	0-90 minutes after dosing
Safety - Time to first rescue infusion	Time to first rescue infusion of IV glucose after trial drug administration	0-90 minutes after dosing
Immunogenicity - Occurrence of anti-drug antibodies	Occurrence of antibodies against dasiglucagon	60 days

Collaborators and Investigators

• Sponsor: Zealand Pharma
• Investigators: Study Director: Stine J Maarbjerg, PHD, Zealand Pharma A/S

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2019
• Primary Completion (Actual): July 30, 2019
• Study Completion (Actual): July 30, 2019

Study Registration Dates

• First Submitted: March 27, 2019
• First Submitted That Met QC Criteria: March 27, 2019
• First Posted (Actual): March 29, 2019

Study Record Updates

• Last Update Posted (Estimate): February 20, 2023
• Last Update Submitted That Met QC Criteria: February 16, 2023
• Last Verified: February 1, 2023

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: ZP4207-17084

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No