Clinical trial NCT02562313: A Trial Investigating the Continuous Subcutaneous Insulin Infusion of a Liquid Formulation of BioChaperone Insulin Lispro in Comparison to Humalog®
Official title: A Trial Investigating the Continuous Subcutaneous Insulin Infusion of a Liquid Formulation of BioChaperone Insulin Lispro in Comparison to Humalog®
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 1 Diabetes Mellitus
Lead sponsor: Adocia
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2015-09-29
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Pharmacodynamics: ΔAUCBG 0-2h
timeFrame: 2 Hours
measure: Pharmacokinetics: AUClis 0-30min
timeFrame: 30 minutes
Secondary outcomes:
measure: AUClis_0-6h
timeFrame: up to 6 Hours
measure: Cmax
timeFrame: up to 6 Hours
measure: tCmax
timeFrame: up to 6 Hours
measure: BGmax
timeFrame: up to 6 Hours
measure: tBGmax
timeFrame: up to 6 Hours
measure: Compatibility
timeFrame: up to 14 days
measure: Adverse Events
timeFrame: up to 12 weeks
measure: Local tolerability
timeFrame: up to 12 weeks
Other outcomes:
Locations:
city: Neuss
country: Germany
facility: Profil GmbH
Study officials:
affiliation: Profil GmbH
name: Tim Heise, MD
role: PRINCIPAL_INVESTIGATOR
References: