A Trial to Assess Safety and Efficacy of ADO09 Versus Insulin Aspart in Subjects With Type 1 Diabetes Mellitus

A Randomized, Single-centre, Double-blind, 2-period Cross-over Trial to Assess Safety and Efficacy of ADO09 Versus Insulin Aspart in Subjects With Type 1 Diabetes Mellitus

This is a randomized, double-blind, active-controlled, 2 period cross-over clinical trial in subjects with type 1 diabetes mellitus using a Multiple Daily Injection (MDI) regimen.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: ADO09 formulation; Drug: NovoRapid®

Detailed Description

After a screening visit, eligible subjects will enter a run-in period. Subjects will receive a Continuous Glucose Monitoring (CGM) system for glucose monitoring and control at the beginning of the run-in and for the whole duration of the study. Each eligible subject will then be randomly allocated to a sequence of the 2 treatments, i.e. multiple daily injections of ADO09 and insulin aspart during 2 dosing periods. At Day 1 a mixed meal test (MMT) will be conducted at breakfast and subjects will remain at the clinical site until day 3. At Day 3 subjects will leave the clinical site and continue the treatment with IMP for the next 3 weeks. On Day 23 subjects will come back for a MMT on Day 24.

This study is constituted of 2 parts. In the first part (Part A), only subjects with daily prandial insulin dose ≤ 40 U/day will be enrolled.

Following the completion of the part A, an extension part (Part B) will be conducted to particularly assess the safety and tolerability of higher daily doses of ADO09 in patients with insulin requirements ≥ 40 U/day.

The clinical conduct and procedures will not change for the Extension Part of the study.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2; 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:

• Signed and dated informed consent obtained before any trial-related activities.
• Type 1 diabetes mellitus (as diagnosed clinically) ≥ 12 months.
• Treated with insulin ≥ 12 months.
• Using a multiple dosing insulin therapy (MDI) with basal and bolus insulin.
• HbA1c ≤ 9.0%.
• Fasting negative C-peptide (≤ 0.30 nmol/L).
• Total daily prandial dose: ≤ 40U in the Part A and ≥ 40 U in the Part B

Exclusion Criteria:

• Known or suspected hypersensitivity to products used in the clinical trial
• Type 2 diabetes mellitus
• Previous participation in this trial. Participation is defined as randomized.
• Receipt of any medicinal product in clinical development within 3 months before randomization in this trial.
• 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.
• Presence of clinically significant acute gastrointestinal symptoms (e.g. nausea, vomiting, heartburn or diarrhoea), as judged by the Investigator.
• 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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Co-formulation of insulin analog and pramlintide (ADO09); Subcutaneous injection of ADO09 formulation	Drug: ADO09 formulation; Subcutaneous injection of ADO09 formulation
Active Comparator: NovoRapid®; Subcutaneous injection of insulin aspart	Drug: NovoRapid®; Subcutaneous injection of insulin aspart

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ΔAUCPG(0-4h)	Incremental area under the plasma glucose concentration-time curve from 0-4 hours after start of breakfast, assessed by Super GL at day 24.	From 0 to 4 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of pramlintide	Area under the pramlintide concentration-time curve	From 0 to 4 hours
Pharmacokinetics of insulins	Area under the insulins concentration-time curve	From 0 to 4 hours
Plasma glucose control as measured by CGM	Time and percentage of time in Range (TiR) [70-180] mg/dL	Over 24 hours
Safety and tolerability (Adverse Events recording)	Number of Adverse Events	Up to 24 days

Collaborators and Investigators

• Sponsor: Adocia

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2019
• Primary Completion (Actual): June 27, 2020
• Study Completion (Actual): June 27, 2020

Study Registration Dates

• First Submitted: June 7, 2019
• First Submitted That Met QC Criteria: June 7, 2019
• First Posted (Actual): June 11, 2019

Study Record Updates

• Last Update Posted (Actual): November 30, 2020
• Last Update Submitted That Met QC Criteria: November 27, 2020
• Last Verified: November 1, 2020

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 Aspart
• Other Study ID Numbers: CT038-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