A Trial to Investigate the Efficacy, Pharmacokinetics, Safety and Tolerability of BioChaperone Insulin Lispro in Comparison to Humalog® U-100 in Patients With Type 2 Diabetes Mellitus

A Randomised, Monocentric, Double-blind, Multiple Daily Dose, Two-period 14 Day Cross-over Trial to Investigate the Efficacy, Pharmacokinetics, Safety and Tolerability of Individualised Doses of BioChaperone Insulin Lispro in Comparison to Humalog® U-100 in Patients With Type 2 Diabetes Mellitus

This is a double-blind, randomised, controlled, two-period crossover phase Ib trial using an individualised standard meal with a fixed nutrient ratio in subjects with type 2 diabetes mellitus to investigate post-prandial blood glucose control with BioChaperone insulin lispro compared to insulin lispro (Humalog®, Eli Lilly and Company) before and after a period of multiple daily dose administrations for 14 days. Each subject will be randomised to a sequence of two treatments, either BioChaperone insulin lispro-Humalog® or Humalog®-BioChaperone insulin lispro. Injections will take place immediately before an individualised standard meal in the morning of day 1, 2, 13, and 14. Insulin doses will be determined at the screening visit. During the outpatient phase the subjects will keep their basal insulin constant (except changes for safety reason). They will self-measure blood glucose at least 4 times daily (pre-prandial and at bedtime). In addition, on two days per outpatient period (Day 5 and 9) blood glucose will be measured 7 times daily (pre-prandial, 2 hours post-prandial and at bedtime).

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: BioChaperone insulin lispro; Drug: Humalog®

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Mainz, Germany, 44116
    • Profil Mainz GmbH & Co.KG
  • Neuss, Germany, 41460
    • Profil GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Type 2 diabetes mellitus ≥ 12 months
• Treated with stable multiple daily insulin ≥ 3 months (basal-bolus therapy or only bolus insulin therapy)
• Current total daily insulin treatment <1.2 (I)U/kg/day
• Body Mass Index below or equal to 40.0 kg/m²
• HbA1c ≤ 9.0% by local laboratory analysis

Exclusion Criteria:

• Known or suspected hypersensitivity to trial products or related products
• Type 1 diabetes mellitus
• Previous participation in this trial
• The receipt of any investigational product within 60 days 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
• Presence of renal impairment (Estimated Glomerular filtration Rate (eGFR)<60 milliliters/minute/1.73m²)
• Presence of late diabetic complications and/or acute coronary heart disease.
• 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
• Current treatment with corticosteroids

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Humalog®	Drug: Humalog®; Injection immediately before the start of the individualised standard meal
Experimental: BioChaperone insulin lispro	Drug: BioChaperone insulin lispro; Injection immediately before the start of the individualised standard meal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamics: ΔAUCBG 0-2h	Incremental Area Under Blood Glucose concentration-time Curve from 0-2 hours after a meal (comparison between BioChaperone insulin lispro and insulin lispro)	2 hours
Pharmacokinetics: AUClis 0-30min	Area Under the serum insulin Lispro concentration-time Curve 0-30 minutes (comparison between BioChaperone insulin lispro and insulin lispro)	30 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUClisp_0-6h	Area Under the serum insulin Lispro concentration-time Curve from 0-6 hours after bolus dose	up to 6 hours
Cmax_lisp	Maximum serum insulin lispro Concentration	up to 6 hours
tmax_lisp	Time to maximum observed serum insulin lispro concentration	up to 6 hours
CmaxBG	Maximum Blood Glucose after an individualised standard meal	up to 6 hours
AUCBG_0-6h	Area Under the Curve under the Blood Glucose concentration time curve from 0-6 hours	up to 6 hours
Adverse Events	Number of Adverse Events	up to 8 weeks
Local tolerability	Record of injection site reaction	up to 8 weeks

Collaborators and Investigators

• Sponsor: Adocia
• Collaborators: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 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): April 29, 2016
• Last Update Submitted That Met QC Criteria: April 28, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin Lispro
• Other Study ID Numbers: BC3-CT014