A Trial to Assess a Co-formulation of an Insulin Analog and Pramlintide in Subjects With Type 1 Diabetes Mellitus

Study Overview
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Brief Summary
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This trial is a monocentric, randomised, double-blind, active comparator, controlled, 3-period cross-over trial.

Detailed Description
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In this monocentric, randomised, double-blind, active comparator, controlled, cross-over trial, each patient will be randomly allocated to a sequence of three treatments: one single dose of the co-formulation of insulin analog and pramlintide (also called ADO09), simultaneous separate injections of pramlintide and human insulin and one single dose of insulin lispro. To keep the blinding in this trial, a placebo injection will be given in addition to the ADO09 formulation and insulin lispro dose for a total of 2 injections per dosing visit. During each visit, meal test procedures will be performed and subjects will stay at the clinical centre until post-dose follow-up period has been terminated. IMP administration will be done subcutaneously immediately prior to test meal intake.

Official Title
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A Trial to Investigate Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of a Co-formulation of an Insulin Analog and Pramlintide in Subjects With Type 1 Diabetes Mellitus

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: ADO09 formulation
* Drug: Placebo
* Drug: Symlin®
* Drug: Humulin®
* Drug: Humalog®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 1 Diabetes Mellitus (as diagnosed clinically) ≥ 12 months Treated with multiple daily injection ≥ 12 months Treated with insulin glargine U100 or U300 or insulin detemir at screening Fasting C-peptide ≤ 0.30 nmol/L BMI: 18.5-28.0 kg/m² (both inclusive) Exclusion Criteria: Known or suspected hypersensitivity to IMPs, paracetamol or related products Type 2 Diabetes Mellitus Clinically significant abnormal haematology, biochemistry or urinalysis screening test, 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: Co-formulation of insulin analog and pramlintide (ADO09)<br>Subcutaneous injection of ADO09 formulation + injection of placebo (0.9% NaCl) to ensure double dummy. | Drug: ADO09 formulation<br>* Subcutaneous injection of ADO09 formulation<br>Drug: Placebo<br>* Subcutaneous injection of 0.9% NaCl<br>|
| Active Comparator: Humulin® + Symlin®<br>Simultaneous, separate subcutaneous injections of human insulin and pramlintide. | Drug: Symlin®<br>* Subcutaneous injection of pramlintide<br>Drug: Humulin®<br>* Subcutaneous injection of human insulin<br>|
| Active Comparator: Humalog®<br>Subcutaneous injection of insulin lispro + injection of placebo (0.9% NaCl) to ensure double dummy. | Drug: Placebo<br>* Subcutaneous injection of 0.9% NaCl<br>Drug: Humalog®<br>* Subcutaneous injection of insulin lispro<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 | 
| CmaxIns | Maximum insulin analog concentration | From 0 to 8 hours | 
| AUCIns 0-8h | Area under the insulin analog 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 insulins 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 |