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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Hypoglycemia, Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: dasiglucagon


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glucagon