To Investigate the Efficacy and Safety of Individualized Doses of BioChaperone Insulin Lispro in Comparison to Humalog® U-100 in Patients With Type 1 Diabetes Mellitus

A Randomized, Monocentric, Double-blind, Multiple Daily Dose, Two-period, 14 Day Cross-over Trial to Investigate the Efficacy, Pharmacokinetics, Safety and Tolerability of Individualized Doses of BioChaperone Insulin Lispro in Comparison to Humalog® U-100 in Patients With Type 1 Diabetes Mellitus

This is a double-blind, randomised, controlled, two period crossover phase Ib trial using an individualized standard meal with a fixed nutrient ratio in subjects with type 1 diabetes mellitus to investigate postprandial blood glucose control with BioChaperone insulin lispro compared to Humalog®. The assessments will be conducted before and after a period of multiple daily dose administrations for 14 days. The meal tolerance test will be performed on day 1-3 and on day 14 of each period. Furthermore the study aims at investigating Post-prandial glucose (PPG) profiles with BioChaperone insulin lispro and Humalog® when injected at various injection meal intervals (-15min, 0 minutes, +15 minutes).

Each subject will be randomised to a sequence of two treatments, either BioChaperone insulin lispro-Humalog® or Humalog®-Biochaperone insulin lispro, and three different sequences of injection-meal intervals. A blinded to patient continuous monitoring of glucose (CGM) will be performed during the 14 day treatment periods.

Inclusion Criteria:

• Type 1 diabetes mellitus (as diagnosed clinically) ≥ 12 months
• Treated with multiple daily insulin injections (no pump users) ≥ 12 months
• Current total daily insulin treatment <1.2 (I)U/kg/day
• Body mass index (BMI) 18.5-28.0 kg/m² (both inclusive)
• HbA1c (N-(1-deoxy)-fructosyl-haemoglobin) ≤ 9.0% by local laboratory analysis
• Fasting C-peptide ≤ 0.30 nmol/L

Exclusion Criteria:

• Known or suspected hypersensitivity to trial products or related products
• Type 2 diabetes mellitus
• Patients using continuous subcutaneous insulin infusion (CSII)
• Previous participation in this trial. Participation is defined as randomised
• The receipt of any investigational product within 3 months prior to this trial
• Clinically significant abnormal haematology, biochemistry, lipids, or urinalysis screening tests, 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 and or gastrointestinal surgery that in the opinion of the investigator might change gastrointestinal motility and food absorption
• Unusual meal habits and special diet requirements or unwillingness to eat the food provided in the trial