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

Phase 3
Completed
Conditions
Diabetes Mellitus, Type 1
Hypoglycemia
Interventions
Registration Number
NCT03895697
Lead Sponsor
Zealand Pharma
Brief Summary

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)

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
92
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 & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Dasiglucagon batch A crossover to dasiglucagon batch BdasiglucagonV2: Single fixed dose (subcutaneous injection) of dasiglucagon batch A then at V3: Single fixed dose (subcutaneous injection) of dasiglucagon batch B
Dasiglucagon batch B crossover to dasiglucagon batch AdasiglucagonV2: Single fixed dose (subcutaneous injection) of dasiglucagon batch B then at V3: Single fixed dose (subcutaneous injection) of dasiglucagon batch A
Primary Outcome Measures
NameTimeMethod
Time to plasma glucose recovery0-45 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 intravenous glucose

Secondary Outcome Measures
NameTimeMethod
Pharmacokinetics - Maximum plasma concentration0-300 minutes after dosing

Measured maximum plasma drug concentration after dosing, Cmax

Pharmacodynamics - Maximum plasma glucose concentration0-90 minutes after dosing

Change from baseline plasma glucose to maximum plasma glucose measure after dosing, CEmax

Pharmacokinetics - Area under the plasma concentration-time curve 30 min0-30 minutes after dosing

Area under the concentration-time curve (AUC) from zero up to the concentration at 30 minutes, AUC0-30min

Pharmacokinetics - Area under the plasma concentration-time curve 300 min0-300 minutes after dosing

Area under the concentration-time curve (AUC) from zero up to the concentration at 300 minutes, AUC0-300min

Pharmacokinetics - Body clearance0-300 minutes after dosing

Total body clearance, CL/f

Safety - Adverse events90 days

The incidence, type and severity of adverse events (AEs)

Plasma glucose changes from baseline0-30 minutes after dosing

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).

Pharmacodynamics - Area under the effect curve 30 min0-30 minutes after dosing

Area under the baseline-adjusted effect curve (AUE) from zero up to the concentration at 30 minutes, AUE 0-30min

Pharmacodynamics - Area under the effect curve 90 min0-90 minutes after dosing

Area under the baseline-adjusted effect curve (AUE) from zero up to the concentration at 90 minutes, AUE 0-90min

Pharmacokinetics - Mean residence time0-300 minutes after dosing

Mean residence time, MRT

Safety - Number of rescue infusions0-90 minutes after dosing

Number of rescue infusions of IV glucose after trial drug administration

Pharmacodynamics - Time maximum plasma glucose concentration0-90 minutes after dosing

Time to maximum change in plasma glucose measure from baseline, TEmax

Pharmacokinetics - Area under the plasma concentration curve Infinitely0-300 minutes after dosing

Area under the concentration-time curve from zero up to the concentration at infinitely after dosing, AUC0-inf

Safety - Time to first rescue infusion0-90 minutes after dosing

Time to first rescue infusion of IV glucose after trial drug administration

Immunogenicity - Occurrence of anti-drug antibodies60 days

Occurrence of antibodies against dasiglucagon

Pharmacokinetics - Time to maximum plasma concentration0-300 minutes after dosing

Sampling time until reaching Cmax, Tmax

Pharmacokinetics - Half-life0-300 minutes after dosing

Half-life dasiglucagon, t½

Pharmacokinetics - Volume of distribution0-300 minutes after dosing

Apparent volume of distribution of dasiglucagon, Vz/f

Trial Locations

Locations (1)

LMC Diabetes & Manna Research

🇨🇦

Toronto, Ontario, Canada

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