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

Phase 1
Completed
Conditions
Type 1 Diabetes
Interventions
Drug: Administration of BioChaperone insulin lispro reconstituted with Humalog® (IMP1)
Drug: Administration of Ready-to-use BioChaperone insulin lispro (IMP2)
Drug: Administration of US-approved Humalog® (IMP3)
Drug: Administration of EU-approved Humalog® (IMP4)
Registration Number
NCT04501107
Lead Sponsor
Adocia
Brief 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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
32
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
BioChaperone insulin lispro reconstituted with Humalog® (IMP1)Administration of BioChaperone insulin lispro reconstituted with Humalog® (IMP1)Subcutaneous administration of Biochaperone insulin lispro formulation made from a freeze-dried of BioChaperone reconstituted with Humalog® at a dose of 0.2 U/Kg Body Weight (BW).
Ready-to-use BioChaperone insulin lispro (IMP2)Administration of Ready-to-use BioChaperone insulin lispro (IMP2)Subcutaneous administration of ready-to-use Biochaperone insulin lispro formulation at a dose of 0.2 U/Kg BW.
US-approved Humalog® (IMP3)Administration of US-approved Humalog® (IMP3)Subcutaneous administration of US-approved Humalog® at a dose of 0.2 U/Kg BW.
EU-approved Humalog® (IMP4)Administration of EU-approved Humalog® (IMP4)Subcutaneous administration of EU-approved Humalog® at a dose of 0.2 U/Kg BW.
Primary Outcome Measures
NameTimeMethod
AUCGIR.0-1hFrom t=0 to t=1 hour after IMP administration

Area under the glucose infusion rate-time curve from time 0 to 1 hour after IMP administration

AUCGIR.0-12hFrom t=0 to t=12 hours after IMP administration

Area under the glucose infusion rate-time curve from time 0 until end of clamp

AUCLIS.0-1hFrom t=0 to t=1 hour after IMP administration

Area under the insulin lispro concentration-time curve from 0 hours to 1 hour after dose administration

AUCLIS.0-12hFrom t=0 to t=12 hours after IMP administration

Area under the insulin lispro concentration-time curve from 0 hours to 12 hours after dose administration

Secondary Outcome Measures
NameTimeMethod
t50%-LIS (early)From t=0 to t=12 hours after IMP administration

Time to half-maximum before Cmax.LIS

Cmax.LISFrom t=0 to t=12 hours after IMP administration

Maximum observed insulin lispro concentration

tmax.LISFrom t=0 to t=12 hours after IMP administration

Time to maximum observed insulin lispro concentration

AUCLIS.2-6hFrom t=2 to t=6hours after IMP administration

Area under the insulin lispro concentration-time curve from 2 hour to 6 hour after dose administration

tmax.GIRFrom t=0 to t=12 hours after IMP administration

Time to maximum glucose infusion rate

GIRmaxFrom t=0 to t=12 hours after IMP administration

Maximum glucose infusion rate

AUCGIR.4-8hFrom t=4 to t=8 hours after IMP administration

Area under the glucose infusion rate-time curve from 4 to 8 hours after dose administration

Trial Locations

Locations (1)

Profil GmbH

🇩🇪

Mainz, Germany

Profil GmbH
🇩🇪Mainz, Germany

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