A Trial to Investigate Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of BioChaperone® Pramlintide Insulin in Patients With Type 1 Diabetes Mellitus

Study Overview
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Brief Summary
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This is a single center, randomised, double-blind, active comparator controlled, three-period cross-over, single dose trial in subjects with type 1 diabetes mellitus.

Detailed Description
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This is a single center, randomised, double-blind, active comparator controlled, three-period cross-over, single dose trial in subjects with type 1 diabetes mellitus. Each subject will be randomly allocated to a sequence of three treatments:(i) simultaneous administrations of BioChaperone® pramlintide human insulin (BC Pram Ins) and placebo, (ii) simultaneous injections of pramlintide (Symlin®) and human insulin (Humulin®) and (iii) simultaneous injections of insulin lispro (Humalog®) and placebo. Subjects will come in a fasted state to the clinical trial centre in the morning, meal test procedures will be performed and subjects will stay at the clinical trial centre until the post-dose follow-up period has been terminated.

Official Title
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A Trial to Investigate Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of BioChaperone® Pramlintide Insulin in Patients With Type 1 Diabetes Mellitus

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: BC Pram Ins
* Drug: Symlin® and Humulin®
* Drug: Humalog®
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects aged 18-64 years (both inclusive) Type 1 diabetes mellitus (as diagnosed clinically) ≥ 12 months Treated with multiple daily insulin injections ≥ 12 months Treated with an evening dose of once-daily insulin glargine U100 at screening Fasting C-peptide ≤ 0.30 nmol/L Exclusion Criteria: Known or suspected hypersensitivity to IMPs, paracetamol (acetaminophen) or related products Type 2 diabetes mellitus Clinically significant abnormal haematology, biochemistry, or urinalysis screening tests, as judged by the Investigator considering the underlying disease Presence of clinically significant acute gastrointestinal symptoms (e.g. nausea, vomiting, heartburn or diarrhoea), as judged by the Investigator Known slowing of gastric emptying, including gastroparesis, and or gastrointestinal surgery that in the opinion of the investigator might change gastrointestinal motility and food absorption Intake of medication known to affect gastrointestinal motility, including but not limited to erythromycin, metoclopramide, cisapride, cholestyramine or colestipol within 4 weeks before screening

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BC Pram Ins<br>Single subcutaneous injection of BC Pram Ins + injection of placebo (0.9% NaCl) to ensure the double dummy | Drug: BC Pram Ins<br>* Injection of BC Pram Ins<br>Drug: Placebo<br>* Injection of 0.9% NaCl<br>|
| Active Comparator: Symlin® and Humulin®<br>Simultaneous subcutaneous injections avec pramlintide and human insulin | Drug: Symlin® and Humulin®<br>* Injection of pramlintide and human insulin<br>|
| Active Comparator: Humalog®<br>Single subcutaneous injection of lispro + injection of placebo (0.9% NaCl) to ensure the double dummy | Drug: Humalog®<br>* Injection of lispro<br>Drug: Placebo<br>* Injection of 0.9% NaCl<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CmaxPram | Maximum pramlintide concentration | From 0 to 8 hours | 
| AUCPram_0-8h | Area Under the pramlintide concentration-time Curve from 0-8 hours after IMP administration | From 0 to 8 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of pramlintide | Area Under the pramlintide concentration-time Curve | From 0 to 8 hours | 
| Pharmacokinetics of insulins | Area Under the insulin concentration-time Curve | From 0 to 8 hours | 
| Glucose pharmacodynamics | Area Under the blood glucose concentration-time Curve | From 0 to 8 hours | 
| Safety and tolerability (Adverse Events recording) | Number of adverse events | From 0 to 8 hours |