A Trial Investigating the Continuous Subcutaneous Insulin Infusion of a Liquid Formulation of BioChaperone Insulin Lispro in Comparison to Humalog®

This study is constituted of 2 parts:

Part A: A total of 36 patients will be enrolled in part A. Each eligible subject will participate in two 14-day treatment periods with Continuous Subcutaneous Insulin Infusion (CSII) of BioChaperone insulin lispro and insulin lispro (Humalog®, Eli Lilly and Company). Each treatment period consists of 10 treatment days under free living conditions (e.g. home / workplace) and under standardised conditions at the clinic. Various assessments for pharmacodynamics, pharmacokinetics, pump compatibility, short-term efficacy and safety are performed on selected days, including:

• Mixed Meal Test (MMT), Day 1, Day 3, Day 12 and Day 14, that will assess the post-prandial glucose response for 6 hours after individualized standard meal (fixed nutrient ratio) ingestion and bolus administration via CSII.
• Continuous Glucose Monitoring (CGM), (Day 1 - 14) that will be used in blinded mode (i.e. neither subjects nor the investigators are aware of the sensor glucose values).
• Pump compatibility (Day 1 - 14): Subjects will continue CSII treatment with the Investigational Medicinal Products (IMP) during the outpatient periods.

Part B: A total of 44 patients will be enrolled. Subjects will be randomized to a 4-period cross-over study aiming at comparing the performance of BC Lispro and Humalog after a prandial bolus administration with two different CSII systems (Roche Accu-Chek® Spirit and Medtronic Paradigm® Veo™) or with a syringe. Pharmacodynamics, pharmacokinetics, pump compatibility and safety will be analyzed.

Each period will include a mixed meal tolerance test with a CSII device and a mixed meal tolerance test with the same dose of insulin administered with a syringe.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 80
• 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 for at least 12 months
• Body Mass Index (BMI) between 18.5 and 28.5 kg/m^2, both inclusive
• Using or having used a Roche CSII system (Accu-Chek® Spirit Combo/ Accu- Chek® Spirit) for at least 6 months before screening. In Part B subjects using any form of CSII treatment for at least 6 months before screening will be included.
• HbA1c <= 9.0%.
• Total insulin dose of < 1.2 (I)U/kg/day
• Ability to calculate insulin bolus manually or using a bolus calculator and willingness to consume regular meals, perform carbohydrate counting, self-monitoring of plasma glucose (SMPG) profiles and use of Continuous Glucose Monitoring (CGM).
• Fasting C-peptide <= 0.30 nmol/L

Exclusion Criteria:

• Known or suspected hypersensitivity to Investigational Medicinal Product(s) (IMP(s)) or related products
• Type 2 diabetes mellitus
• Previous participation in this trial.
• Receipt of any investigational product in a clinical trial within 60 days before randomisation in this trial
• Clinically significant abnormal haematology, biochemistry, urinalysis, or coagulation screening test
• Presence of clinically significant acute gastrointestinal symptoms
• Known slowing of gastric emptying and or gastrointestinal surgery
• Unusual meal habits and special dietary requirements or unwillingness to eat the food provided in the trial
• History of diabetic ketoacidosis (DKA) episodes requiring hospitalization within 6 months prior to screening
• History of abscess at the infusion site within 6 months prior to screening
• Hypoglycaemia unawareness as judged by the Investigator
• History of severe hypoglycaemic episodes requiring hospitalization within the last 6 months prior to screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BioChaperone insulin lispro	Drug: BioChaperone insulin lispro; BioChaperone insulin lispro bolus infusion followed by test meal intake
Active Comparator: Humalog®; Insulin lispro	Drug: Humalog®; Humalog® bolus infusion followed by test meal intake

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamics: ΔAUCBG 0-2h	Incremental Area Under the Blood Glucose concentration-time Curve from 0-2 hours after the start of the meal.	2 Hours
Pharmacokinetics: AUClis 0-30min	Area Under the serum insulin Lispro concentration-time Curve from 0-30 minutes	30 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUClis_0-6h	Area Under the baseline adjusted insulin Lispro Curve from 0-6h following a bolus dose	up to 6 Hours
Cmax	Maximum insulin Concentration following a bolus dose	up to 6 Hours
tCmax	Time to Maximum insulin Concentration following a bolus dose	up to 6 Hours
BGmax	Maximum Blood Glucose after start of an individualised standardised meal intake	up to 6 Hours
tBGmax	Time to Maximum Blood Glucose concentration	up to 6 Hours
Compatibility	Number of suspected episodes of infusion set occlusion or leakage	up to 14 days
Adverse Events	Number of Adverse Events	up to 12 weeks
Local tolerability	Number of injection site reactions	up to 12 weeks

Collaborators and Investigators

• Sponsor: Adocia
• Collaborators: Eli Lilly and Company
• Investigators: Principal Investigator: Tim Heise, MD, Profil GmbH

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: September 28, 2015
• First Submitted That Met QC Criteria: September 28, 2015
• First Posted (Estimate): September 29, 2015

Study Record Updates

• Last Update Posted (Estimate): November 22, 2016
• Last Update Submitted That Met QC Criteria: November 21, 2016
• Last Verified: November 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-CT015