A Trial to Investigate the Dose-linearity of BioChaperone® Combo 75/25 and the Safety at Three Different Doses in Subjects With Type 2 Diabetes

A Double-blinded, Randomised, Four-period Crossover Euglycemic Clamp Trial Investigating the Dose-linearity of BioChaperone® Combo 75/25 and the Safety at Three Different Doses in Subjects With Type 2 Diabetes

This is a bicentric, double-blinded, randomised, four-period crossover phase 1 trial, using automated 30-hour euglycemic clamp in subjects with type 2 diabetes mellitus.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: BioChaperone® Combo 75/25 at 0.6 U/kg; Drug: BioChaperone® Combo 75/25 at 0.8 U/kg; Drug: BioChaperone® Combo 75/25 at 1.0 U/kg; Drug: Humalog® Mix25 at 0.8 U/kg

Detailed Description

This is a bicentric, double-blinded, randomised, four-period crossover phase 1 trial, using automated 30-hour euglycemic clamp in subjects with type 2 diabetes mellitus.

Each subject will be randomly allocated to a sequence of four treatments, three single doses of BioChaperone® Combo 75/25 (0.6 U/kg, 0.8 U/kg or 1.0 U/kg) and one single dose of Humalog® Mix25 at 0.8 U/kg on four separate dosing visits.

Subjects will come in a fasted state to the clinical trial centre in the morning of each dosing day and stay at the clinical trial centre until the 30-hour clamp procedures have been terminated.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Mainz, Germany
    • Profil Mainz GmbH & Co. KG
  • Neuss, Germany
    • Profil Institut für Stoffwechselforschung GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subject aged 18-70 years (both inclusive)
• Type 2 diabetes mellitus (as diagnosed clinically) for ≥ 12 months
• HbA1c level between 6.5% and 9.0 % (both inclusive)
• Body mass index between 20.0 and 40.0 kg/m2 (both inclusive)
• Body weight <= 125.0 kg at the screening visit
• Insulin-treated subjects. Total insulin dose of <= 1.2 (I)U/kg/day

Exclusion Criteria:

• Type 1 diabetes mellitus
• Known or suspected hypersensitivity to IMP(s) or related products
• Previous participation in this trial. Participation is defined as randomised.
• Receipt of any medicinal product in clinical development within 60 days before randomisation in this trial.
• Clinically significant abnormal values for haematology, biochemistry, coagulation, or urinalysis as judged by the Investigator considering the underlying disease.
• Supine blood pressure at screening (after resting for at least 5 min in supine position) outside the range of 90-160 mmHg systolically or 50-95 mmHg diastolically (excluding white-coat hypertension; therefore, if a repeated measurement shows values within the range, the subject can be included in the trial); symptoms of arterial hypotension and/or a heart rate at rest outside the range of 50-90 beats per minute. This exclusion criterion also pertains to subjects being on anti-hypertensives.
• Women of child bearing potential not willing to use contraceptive methods.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BioChaperone® Combo 75/25 at 0.6 U/kg; Single subcutaneous injection of 0.6 U/kg	Drug: BioChaperone® Combo 75/25 at 0.6 U/kg; Injection of BioChaperone® Combo 75/25 at 0.6 U/kg
Experimental: BioChaperone® Combo 75/25 at 0.8 U/kg; Single subcutaneous dose of 0.8 U/kg	Drug: BioChaperone® Combo 75/25 at 0.8 U/kg; Injection of BioChaperone® Combo 75/25 at 0.8 U/kg
Experimental: BioChaperone® Combo 75/25 at 1.0 U/kg; Single subcutaneous dose of 1.0 U/kg	Drug: BioChaperone® Combo 75/25 at 1.0 U/kg; Injection of BioChaperone® Combo 75/25 at 1.0 U/kg
Active Comparator: Humalog® Mix25 at 0.8 U/kg; Single subcutaneous dose of 0.8 U/kg	Drug: Humalog® Mix25 at 0.8 U/kg; Injection of Humalog® Mix25 at 0.8 U/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC last_total	Area under the plasma insulin concentration-time curve from t=0 to the last measured total insulin plasma concentration above LLOQ. The total insulin concentration is the sum of lispro and basal concentrations.	From 0 to 30 hours
Cmax_total	Maximum observed plasma insulin total concentration	From 0 to 30 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUCGIR 0-last (mg/kg)	Area under the glucose infusion rate curve from 0 hours until the end of clamp	From 0 to 30 hours
GIRmax (mg/kg/min)	Maximum glucose infusion rate	From 0 to 30 hours
tGIRmax	Time to maximum glucose infusion rate	From 0 to 30 hours
Adverse Events		Up to 102 days (maximum duration of subject's participation)
Local tolerability: number of injection site reaction	Frequency of injection site reaction in each arm.	Up to 102 days (maximum duration of subject's participation)
Number of hypoglycaemic events in each treatment arm		Up to 102 days (maximum duration of subject's participation)

Collaborators and Investigators

• Sponsor: Adocia

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2017
• Primary Completion (Actual): August 28, 2017
• Study Completion (Actual): December 21, 2017

Study Registration Dates

• First Submitted: June 6, 2017
• First Submitted That Met QC Criteria: June 7, 2017
• First Posted (Actual): June 8, 2017

Study Record Updates

• Last Update Posted (Actual): January 10, 2018
• Last Update Submitted That Met QC Criteria: January 9, 2018
• Last Verified: January 1, 2018

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-CT025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No