A Trial to Investigate the Safety and the Pharmacokinetic, Pharmacodynamic Characteristics of Two BioChaperone® Glucagon Formulations Compared to Marketed GlucaGen® in Subjects With T1DM

Study Overview
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Brief Summary
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This is a single centre, double-blind, randomised, three-period crossover phase 1 trial in subjects with type 1 diabetes mellitus (T1DM). Each subject will be randomly allocated to a sequence of three treatments, i.e. two single subcutaneous doses of BioChaperone® Glucagon (BC Glucagon) formulation 1, BioChaperone® Glucagon formulation 2 and GlucaGen® HypoKit®, each at the fixed doses of 50 µg and 1 mg on 3 separate dosing visits. Following trial drug administration, pharmacokinetics (PK) and pharmacodynamics (PD) assessments will be carried until 4 hours. Safety will be assessed during all the trial period. The total trial maximum duration for the individual subject will be up to 10 weeks.

Official Title
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A Randomised, Double-blind, Three-period Crossover Trial to Investigate the Safety and the Pharmacokinetic, Pharmacodynamic Characteristics of Two BioChaperone® Glucagon Formulations Compared to Marketed GlucaGen® in Subjects With Type 1 Diabetes

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: BioChaperone® glucagon formulation 1
* Drug: BioChaperone® glucagon formulation 2
* Drug: GlucaGen® HypoKit®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients aged between 18 and 64 years (both inclusive) Type 1 diabetes mellitus (as diagnosed clinically) ≥ 12 months prior to the screening visit Treated with daily insulin for T1DM ≥ 12 months prior to the screening visit Stable insulin treatment at least 3 months prior to the screening visit Stable disease with HbA1c <9.0 % C peptide <=0.30 nmol/L Body mass index (BMI) < 30.0 kg/m2 Exclusion Criteria: Type 2 Diabetes mellitus Previous participation in this trial. Participation is defined as being randomised Receipt of any medicinal product in clinical development within 60 days prior to this trial Clinically significant abnormal haematology, biochemistry, urinalysis, or coagulation screening tests, as judged by the Investigator considering the underlying disease Known or suspected hypersensitivity to the trial products or related products Severe hypoglycaemic events within one month prior to screening, as judged by the investigator Recent administration of glucagon (within 3 months prior to Screening) Clinically relevant diabetic complications as judged by the investigator Women of child bearing potential not willing to use contraceptive methods

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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: BioChaperone® glucagon formulation 1<br>Single subcutaneous fixed doses (50 µg and 1.0 mg) | Drug: BioChaperone® glucagon formulation 1<br>* Injection of BioChaperone® glucagon formulation 1 at Day 1: 50 µg and at Day 2: 1 mg<br>|
| Experimental: BioChaperone® glucagon formulation 2<br>Single subcutaneous fixed doses (50 µg and 1.0 mg) | Drug: BioChaperone® glucagon formulation 2<br>* Injection of BioChaperone® glucagon formulation 2 at Day 1: 50 µg and at Day 2: 1 mg<br>|
| Active Comparator: GlucaGen® HypoKit®<br>Single subcutaneous fixed doses (50 µg and 1.0 mg) | Drug: GlucaGen® HypoKit®<br>* Injection of GlucaGen® HypoKit® at Day 1: 50 µg and at Day 2: 1 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical safety laboratory | Haematology, biochemistry and urinalysis: changes or findings from baseline in clinical safety laboratory parameters during the trial duration (screening visit, treatment visits and follow up visit) | Up to 10 weeks | 
| Physical examination | Examination of the body systems | Up to 10 weeks | 
| ECG parameters | Heart rate, PQ, QRS, QT, QTcB: changes or findings from baseline in ECG parameters during the trial duration (screening visit, treatment visits and follow up visit) | Up to 10 weeks | 
| Vital signs | Diastolic and systolic blood pressure (mmHg), Pulse (beats/min), Body temperature (°C), Respiratory frequency (RF/min): changes or findings from baseline in vital signs during the trial duration (screening visit, treatment visits and follow up visit) | Up to 10 weeks | 
| Adverse events and serious adverse events | Untoward medical occurrence | Up to 10 weeks | 
| Assessments of local tolerability at injection site | Local reaction at injection site | Up to 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCPK 0-30min | area under the baseline adjusted plasma glucagon concentration curve from 0 to 30 min | From 0 to 30 min | 
| AUC PK 0-4h | area under the baseline adjusted plasma glucagon concentration curve from 0 to 4 h | From 0 to 4 hours | 
| ΔAUCPG 0-30min | area under the baseline adjusted plasma glucose curve from 0 until 30 min | From 0 to 30 min | 
| ΔAUCPG 0-4h | area under the baseline adjusted plasma glucose curve from 0 until 4h | From 0 to 4 hours | 
| ΔPG 30min | baseline adjusted plasma glucose concentration at 30 min | From 0 to 30 min | 
| Percentage of patients achieving a plasma glucose increase of ≥20 mg/dL from baseline within 30 minutes after treatment | only at day 2 | 30 min after drug administration | 
| Time to plasma glucose increase of ≥20 mg/dL from baseline | only at day 2 | Up to 4 hours after drug administration |