A Trial to Compare BioChaperone Insulin Lispro Formulations With US Approved Humalog® and With EU Approved Humalog® in Patients With Type 1 Diabetes Mellitus

Type 1 Diabetes Clinical Trial

Official title:

A Randomised, Double Blind, Crossover Euglycaemic Clamp Trial to Compare BioChaperone Insulin Lispro Formulations With US Approved Humalog® and With EU Approved Humalog® in Patients With Type 1 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04501107
• Other study ID #: CT037-ADO02
• Status: Completed
• Phase: Phase 1
• Start date: August 3, 2020
• Est. completion date: November 3, 2020

Study information

• Verified date: November 2020
• Source: Adocia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a single-centre, randomised, double-blind, 4-way crossover, 4-treatment, euglycaemic clamp study in subjects with Type 1 Diabetes Mellitus (T1DM). Each subject will be randomly allocated to one of four treatment sequences. Each sequence comprises one single dose of each of four IMPs. IMP1 and IMP2 are BioChaperone lispro formulations. They have the same composition and correspond to different development stages of a unique product which is BioChaperone insulin lispro; between them, improvements were made to prepare industrial production. Comparators (IMP3 and IMP4) are US-approved Humalog® and EU-approved Humalog®. All IMPs will be dosed at 0.2 U/Kg of insulin lispro on 4 dosing visits separated by a washout period of 5 to 15 days. The trial will compare the characteristics of BioChaperone insulin lispro fully liquid (IMP2) formulation to US-approved Humalog and EU-approved Humalog.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: November 3, 2020
• Est. primary completion date: November 3, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

Inclusion Criteria:

• Subjects with type 1 Diabetes Mellitus
• Body Mass Index (BMI) between 18.5 and 28.5 kg/m^2, both inclusive
• HbA1c <= 75 mmol/mol (<=9.0%).
• Fasting negative C-peptide (<= 0.30 nmol/L).
• Total insulin dose of < 1.2 (I)U/kg/day.
• Stable insulin regimen (with respect to safety of the subject and scientific integrity of the study) using continuous subcutaneous insulin infusion (CSII) or multiple daily insulin injections (MDI) for at least 2 months.

Exclusion Criteria:

• Known or suspected hypersensitivity to IMP(s) or related products.
• Receipt of any medicinal product in clinical development within 30 days or at least 5 half-lives of the related substances and their metabolites (whichever is longer) before randomisation in this trial.
• History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction.
• Any history or presence of cancer except basal cell skin cancer or squamous cell skin cancer as judged by the Investigator.
• Any history or presence of clinically relevant comorbidity capable of constituting a risk for the subject when participating in the trial or of interfering with the interpretation of data.
• Signs of acute illness as judged by the Investigator.
• Any serious systemic infectious disease during four weeks prior to first dosing of the trial drug, as judged by the Investigator.
• Clinically significant abnormal screening laboratory tests, as judged by the Investigator.
• Proliferative retinopathy or maculopathy as judged by the Investigator based on a recent (<1.5 years) ophthalmologic examination.
• Use of oral antidiabetic drugs (OADs) and/or GLP-1 receptor agonists within 3 months prior to screening.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

Drug:
• Administration of BioChaperone insulin lispro reconstituted with Humalog® (IMP1)
Administration of IMP1 during a 12-hour euglycaemic clamp.
• Administration of Ready-to-use BioChaperone insulin lispro (IMP2)
Administration of IMP2 during a 12-hour euglycaemic clamp.
• Administration of US-approved Humalog® (IMP3)
Administration of IMP3 during a 12-hour euglycaemic clamp.
• Administration of EU-approved Humalog® (IMP4)
Administration of IMP4 during a 12-hour euglycaemic clamp.

Locations

Country	Name	City	State
Germany	Profil GmbH	Mainz

Sponsors (1)

Lead Sponsor	Collaborator
Adocia

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUCGIR.0-12h	Area under the glucose infusion rate-time curve from time 0 until end of clamp	From t=0 to t=12 hours after IMP administration
Primary	AUCGIR.0-1h	Area under the glucose infusion rate-time curve from time 0 to 1 hour after IMP administration	From t=0 to t=1 hour after IMP administration
Primary	AUCLIS.0-12h	Area under the insulin lispro concentration-time curve from 0 hours to 12 hours after dose administration	From t=0 to t=12 hours after IMP administration
Primary	AUCLIS.0-1h	Area under the insulin lispro concentration-time curve from 0 hours to 1 hour after dose administration	From t=0 to t=1 hour after IMP administration
Secondary	tmax.LIS	Time to maximum observed insulin lispro concentration	From t=0 to t=12 hours after IMP administration
Secondary	Cmax.LIS	Maximum observed insulin lispro concentration	From t=0 to t=12 hours after IMP administration
Secondary	AUCLIS.2-6h	Area under the insulin lispro concentration-time curve from 2 hour to 6 hour after dose administration	From t=2 to t=6hours after IMP administration
Secondary	t50%-LIS (early)	Time to half-maximum before Cmax.LIS	From t=0 to t=12 hours after IMP administration
Secondary	tmax.GIR	Time to maximum glucose infusion rate	From t=0 to t=12 hours after IMP administration
Secondary	GIRmax	Maximum glucose infusion rate	From t=0 to t=12 hours after IMP administration
Secondary	AUCGIR.4-8h	Area under the glucose infusion rate-time curve from 4 to 8 hours after dose administration	From t=4 to t=8 hours after IMP administration