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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: BioChaperone insulin lispro; Drug: Humalog®

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Neuss, Germany, 41460
    • Profil 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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Humalog®	Drug: Humalog®; Injection at t0,or t+15 minutes or t-15minutes with test meal
Experimental: BioChaperone insulin lispro	Drug: BioChaperone insulin lispro; Injection at t0,or t+15 minutes or t-15minutes with test meal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUCΔBG0-2h (timepoint 0 = administration of the meal)	Incremental area under the blood glucose (BG) concentration-time curve from 0-2 hours after a meal on day 1-3 [comparison between treatments Biochaperone insulin lispro vs. lispro (Humalog®)]	2 hours
AUClispro 0-30min (timepoint 0 = time of dosing)	Area under the serum insulin lispro concentration-time curve from 0-30 minutes after bolus dose on one of days 1, 2 or 3 (comparison between treatments BioChaperone insulin lispro vs. lispro (Humalog®))	30 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUClispro_0-6h	Area under the serum insulin lispro concentration-time curve from 0-6 hours after bolus dose	6 Hours
Cmax_lispro	Maximum serum insulin lispro concentration	up to 6 Hours
Tmax_lispro	Time to maximum observed serum insulin lispro concentration	up to 6 Hours
AUCBG_0-6h	Area under the curve under the blood glucose (BG) concentration time curve from 0-6 hours	6 Hours
ΔBGmax	Maximum blood glucose (BG) excursion after a standard meal (0-6 hours)	6 Hours
Adverse events	Number of Adverse events	Up to 3 months
Local tolerability injection site reactions	Injection site reactions over 14 days of exposure	14 days

Collaborators and Investigators

• Sponsor: Adocia
• Collaborators: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: August 18, 2015
• First Submitted That Met QC Criteria: August 18, 2015
• First Posted (Estimate): August 19, 2015

Study Record Updates

• Last Update Posted (Estimate): March 16, 2016
• Last Update Submitted That Met QC Criteria: March 14, 2016
• Last Verified: March 1, 2016

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 Lispro
• Other Study ID Numbers: BC3-CT013