A Stable Glucagon Analog Administered by a Bihormonal Closed Loop System

NCT ID: NCT05454709

Last Updated: 2024-01-03

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-29
• Study Completion Date: 2023-12-29

Brief Summary

The main objective is to determine the feasibility of dasiglucagon in a bi-hormonal reactive closed loop system for automated glucose regulation (artificial pancreas; AP®) in patients with diabetes mellitus type 1. Safety parameters and pharmacodynamics are compared between Dasiglucagon and GlucaGen®.

This study is a single-center, double-blinded, randomized, cross over trial in 12 subjects. The subjects will be randomized to receive either dasiglucagon or GlucaGen® for the first three day study period and switch to the alternate treatment after a wash-out treatment.

Detailed Description

Background of the study:

Inreda Diabetic B.V. (Goor, The Netherlands) developed a bi-hormonal reactive closed loop system to automate glucose regulation (artificial pancreas; AP) in patients with diabetes mellitus type 1. In the current CE-marked AP, GlucaGen® (Novo Nordisk, Denmark) is used as glucagon. This glucagon formulation is not stable and therefore fibrillation and infusion set occlusion could occur, resulting in reduced glucagon action with risk for hypoglycemia. Dasiglucagon (Zealand Pharma, Denmark) is a glucagon analog stable in aqueous solution and does therefore not suffer from fibrillation.

Objective of the study:

The main objective is to determine the feasibility of dasiglucagon in the Inreda AP-system. Secondary objectives are to assess safety parameters, differences in pharmacodynamics between dasiglucagon and GlucaGen® and differences in AP related outcomes.

Study design:

This study is a single-center, double-blinded, randomized, cross over trial which will be performed out-patient.

Study population:

The study population will comprise 12 subjects with diabetes type 1 using the AP system. Inclusion criteria are subjects from 18 years and older and treated with the Inreda AP system for a minimum of 1 month.

Intervention:

The intervention contains use of dasiglucagon administered by the Inreda AP-system. The subject will be randomized to receive either dasiglucagon or GlucaGen® during the first three days. After a wash-out period of four days, the subject will be switched to the alternate treatment. During both study periods subjects have to keep a diary, perform exercise, keep a WiFi access point with them, and have some eating restrictions.

Primary study parameters/outcome of the study:

Main parameter to express feasibility is the time in range (3.9 - 10.0 mmol/l), which will be compared between the dasiglucagon and reference glucagon.

Secondary study parameters/outcome of the study:

• Safety will be expressed as side effects of dasiglucagon compared to side effects of GlucaGen.
• The amount of extra food intakes to prevent/ combat hypoglycemia.
• Pharmacodynamics will be expressed in proportion of time spent in hypo-/hyperglycemia, median/mean glucose value, glycemic variability and PD curves, which will all be compared between the dasiglucagon and reference glucagon.
• AP related outcomes will be expressed in daily administered (maintenance) dosage of insulin/glucagon and the percentage of time that the closed loop algorithm is active.

Conditions

Diabetes Mellitus, Type 1

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: QUADRUPLE

Study Groups

Dasiglucagon

Dasiglucagon 1mg/ml solution for subcutaneous injection. Size and frequency of dosing will be determined by the AP algorithm. Duration: 3 days.

Group Type: EXPERIMENTAL

Dasiglucagon

Intervention Type: DRUG

Use of dasiglucagon in the AP system.

GlucaGen

Glucagon 1mg/ml solution for subcutaneous injection. Size and frequency of dosing will be determined by the AP algorithm. Duration: 3 days.

Group Type: ACTIVE_COMPARATOR

GlucaGen

Intervention Type: DRUG

Use of GlucaGen in the AP system.

Interventions

Dasiglucagon

Use of dasiglucagon in the AP system.

Intervention Type: DRUG

GlucaGen

Use of GlucaGen in the AP system.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Diagnosed with diabetes mellitus type 1;

• Treated with the Inreda AP system for a minimum of 1 month;
• Age between 18 and 75 years;
• Adequate contraception is required (only applicable for female participants);
• Willing and able to sign informed consent.

• Treated with SAP or CSII for a minimum of 6 months;
• HbA1c < 97 mmol/mol;
• BMI < 35 kg/m2;
• No use of acetaminophen, as this may influence the sensor glucose measurements.

Exclusion Criteria

• Impaired awareness of hypoglycemia (score ≥ 4) according to Gold and/or Clarke questionnaire [3], [4];

• Pregnancy and/or breastfeeding;
• Use of oral antidiabetic agents;
• Pheochromocytoma;
• Insulinoma;
• Severe liver/heart/renal failure;
• Alcohol abuse;
• Hypersensitivity reactions to dasiglucagon, glucagon or any of the excipients;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Inreda Diabetic B.V.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

G Laverman, MD

Role: PRINCIPAL_INVESTIGATOR

ZGT hospital

Locations

ZGT hospital

Almelo, Overijssel, Netherlands

Countries

Netherlands

Other Identifiers

NL76691.100.22

Identifier Type: -

Identifier Source: org_study_id