Clinical trial NCT00969592: Expanded PK and PD of Insulin Glulisine Versus Insulin Aspart in Healthy Volunteers
Official title: Comparison of Pharmacodynamics and Pharmacokinetics of the Two Fast-acting Insulin Analogs Insulin Glulisine and Insulin Aspart in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes
Keywords: diabetes
Lead sponsor: Profil Institut für Stoffwechselforschung GmbH
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2009-09-01
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: fractional and total glucose infusion rates
timeFrame: 0-1 hours, 0-2 hours, and time to 10% of GIRmax
Secondary outcomes:
measure: fractional and total insulin areas under the curve (AUC)
timeFrame: 0-1 hours, 0-2 hours, 0-10 hours
Other outcomes:
Locations:
city: Neuss
country: Germany
facility: Profil Institut für Stoffwechselforschung GmbH
Study officials:
affiliation: Profil Institut für Stoffwechselforschung GmbH, Neuss, Germany
name: Sabine Arnolds, MD
role: PRINCIPAL_INVESTIGATOR
References: