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

Phase 1

Completed

• Conditions: Type 1 Diabetes Mellitus
• Interventions: Drug: ADO09 formulation; Drug: Symlin®; Drug: Placebo; Drug: Humulin®; Drug: Humalog®

• Registration Number: NCT03916640
• Lead Sponsor: Adocia

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study Start: 2019-01-04
• Primary Completion: 2019-03-01
• Study Completion: 2019-03-01
• Status Verified: 2019-04
• Study First Submitted: 2019-04-12
• Study First Submitted QC: 2019-04-12
• Last Update Submitted: 2019-04-12
• Study First Posted: 2019-04-16
• Last Update Posted: 2019-04-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

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)

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Co-formulation of insulin analog and pramlintide (ADO09)	ADO09 formulation	Subcutaneous injection of ADO09 formulation + injection of placebo (0.9% NaCl) to ensure double dummy.
Co-formulation of insulin analog and pramlintide (ADO09)	Placebo	Subcutaneous injection of ADO09 formulation + injection of placebo (0.9% NaCl) to ensure double dummy.
Humulin® + Symlin®	Symlin®	Simultaneous, separate subcutaneous injections of human insulin and pramlintide.
Humulin® + Symlin®	Humulin®	Simultaneous, separate subcutaneous injections of human insulin and pramlintide.
Humalog®	Placebo	Subcutaneous injection of insulin lispro + injection of placebo (0.9% NaCl) to ensure double dummy.
Humalog®	Humalog®	Subcutaneous injection of insulin lispro + injection of placebo (0.9% NaCl) to ensure double dummy.

Primary Outcome Measures

Name	Time	Method
CmaxPram	From 0 to 8 hours	Maximum pramlintide concentration
AUCPram 0-8h	From 0 to 8 hours	Area under the pramlintide concentration-time curve from 0-8 hours after IMP administration
CmaxIns	From 0 to 8 hours	Maximum insulin analog concentration
AUCIns 0-8h	From 0 to 8 hours	Area under the insulin analog concentration-time curve from 0-8 hours after IMP administration

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics of pramlintide	From 0 to 8 hours	Area under the pramlintide concentration-time curve
Glucose pharmacodynamics	From 0 to 8 hours	Area under the blood glucose concentration-time curve
Pharmacokinetics of insulins	From 0 to 8 hours	Area under the insulins concentration-time curve
Safety and tolerability (Adverse Events recording)	From 0 to 8 hours	Number of Adverse Events

Trial Locations

Locations (1)

Profil Institut für Stoffwechselforschung GmbH; 🇩🇪 Neuss, Germany