Expanded PK and PD of Insulin Glulisine Versus Insulin Aspart in Healthy Volunteers

Comparison of Pharmacodynamics and Pharmacokinetics of the Two Fast-acting Insulin Analogs Insulin Glulisine and Insulin Aspart in Healthy Volunteers

The purpose of this study was to compare the pharmacodynamics (course of the blood glucose-lowering effect and duration of effect) and pharmacokinetics (course of the concentration of study medication in the blood) of a single subcutaneous dose of 0.2 units/kg of insulin glulisine and insulin aspart in a direct head-to-head comparison during two euglycemic glucose clamps in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Diabetes
• Intervention / Treatment: Drug: insulin glulisine, insulin aspart; Drug: insulin aspart, insulin glulisine

Detailed Description

In a previous glucose clamp study with a head-to-head comparison of insulin glulisine and insulin lispro it was shown that the onset of metabolic action was significantly shorter with insulin glulisine than with insulin lispro (while the total metabolic effect was not different). These results were in line with a faster early insulin exposure of insulin glulisine compared to insulin lispro. The primary aim of this study was to investigate whether or not these favorable characteristics of insulin glulisine were also evident in the comparison against insulin aspart. This was the first clinical study realizing a head-to-head comparison between these two insulin analogs.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Neuss, Germany, D-41460
    • Profil Institut für Stoffwechselforschung GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Overtly healthy males or females (Women: contraception, Pearl Index <1%)
• Between the ages of 18 and 65 years
• Body Mass Index of <= 27 kg/m²
• Safety lab within reference range
• Normal blood pressure and heart rate
• Sufficient venous access
• Written informed consent approved by the Ethical Review Board
• HbA1c and fasting plasma glucose in the normal range

Exclusion Criteria:

• Investigative site personnel directly affiliated with this study and their immediate families or the sponsor´s employees
• Within 30 days of the initial dose of study drug had received treatment with a drug that had not received regulatory approval
• Known allergies to insulin or related compounds
• Regular treatment with any drug, both over-the-counter or prescribed
• an abnormality in the 12-lead ECG increasing the risk for participation
• History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs
• Significant active neuropsychiatric disease
• Regular use of drugs of abuse and or positive findings on urinary drug screening
• Evidence of HIV and/or positive antibodies 1 or 2 and or HIV1 antigen
• Evidence of hepatitis B and/or positive hepatitis C antibody
• Evidence of hepatitis B and/or positive hepatitis B surface antigen
• Women with a positive pregnancy test or breastfeeding women
• Blood donation more than 500 mL within the last 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: insulin glulisine, insulin aspart; insulin glulisine administration during first glucose clamp, insulin aspart administration during second glucose clamp	Drug: insulin glulisine, insulin aspart; single subcutaneous dose of 0.2 units per kg body weight of insulin glulisine during first euglycemic glucose clamp, single subcutaneous dose of 0.2 units per kg body weight of insulin aspart during second euglycemic glucose clamp; Other Names: Apidra; NovoRapid
Active Comparator: insulin aspart, insulin glulisine; insulin aspart administration during first euglycemic clamp, insulin glulisine administration during second clamp	Drug: insulin aspart, insulin glulisine; single subcutaneous dose of 0.2 units per kg body weight of insulin aspart during first euglycemic glucose clamp, single subcutaneous dose of 0.2 units per kg body weight of insulin glulisine during second euglycemic glucose clamp; Other Names: Apidra; NovoRapid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
fractional and total glucose infusion rates	0-1 hours, 0-2 hours, and time to 10% of GIRmax

Secondary Outcome Measures

Outcome Measure	Time Frame
fractional and total insulin areas under the curve (AUC)	0-1 hours, 0-2 hours, 0-10 hours

Collaborators and Investigators

• Sponsor: Profil Institut für Stoffwechselforschung GmbH
• Collaborators: Sanofi
• Investigators: Principal Investigator: Sabine Arnolds, MD, Profil Institut für Stoffwechselforschung GmbH, Neuss, Germany

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: August 31, 2009
• First Submitted That Met QC Criteria: August 31, 2009
• First Posted (Estimate): September 1, 2009

Study Record Updates

• Last Update Posted (Estimate): September 2, 2009
• Last Update Submitted That Met QC Criteria: September 1, 2009
• Last Verified: September 1, 2009

More Information

Terms related to this study

• Keywords: diabetes
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin, Long-Acting; Insulin degludec, insulin aspart drug combination; Insulin glulisine
• Other Study ID Numbers: 49-0361-GluAsp