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

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

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

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: ADO09 formulation; Drug: Placebo; Drug: Symlin®; Drug: Humulin®; Drug: Humalog®

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 Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Neuss, Germany, 41460
    • Profil Institut für Stoffwechselforschung GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Co-formulation of insulin analog and pramlintide (ADO09); Subcutaneous injection of ADO09 formulation + injection of placebo (0.9% NaCl) to ensure double dummy.	Drug: ADO09 formulation; Subcutaneous injection of ADO09 formulation; Drug: Placebo; Subcutaneous injection of 0.9% NaCl
Active Comparator: Humulin® + Symlin®; Simultaneous, separate subcutaneous injections of human insulin and pramlintide.	Drug: Symlin®; Subcutaneous injection of pramlintide; Drug: Humulin®; Subcutaneous injection of human insulin
Active Comparator: Humalog®; Subcutaneous injection of insulin lispro + injection of placebo (0.9% NaCl) to ensure double dummy.	Drug: Placebo; Subcutaneous injection of 0.9% NaCl; Drug: Humalog®; Subcutaneous injection of insulin lispro

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Adocia

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2019
• Primary Completion (Actual): March 1, 2019
• Study Completion (Actual): March 1, 2019

Study Registration Dates

• First Submitted: April 12, 2019
• First Submitted That Met QC Criteria: April 12, 2019
• First Posted (Actual): April 16, 2019

Study Record Updates

• Last Update Posted (Actual): April 16, 2019
• Last Update Submitted That Met QC Criteria: April 12, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin Lispro
• Other Study ID Numbers: CT034-ADO09

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No