Metabolic Effect of Insulin Aspart and Human Insulin in Different Doses

Pharmacodynamic and Pharmacokinetic Properties of Insulin Aspart: Dose - Ranging vs. Human Soluble Insulin

The metabolic effect of three different doses of insulin aspart and human insulin are investigated with the euglycaemic glucose clamp technique.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Drug: insulin aspart; Drug: human regular insulin

Detailed Description

Double-blind, randomized, 6-period cross-over study in 16 healthy subjects. Each patient participates in 6 euglycemic glucose clamp experiments each.

The time interval between the study days is 2 to 28 days. At the clamp visits, subjects are connected to a Biostator (MTB Medizintechnik, Ulm, Germany) and receive an intravenous human insulin infusion (rate of 0.15 mU/kg/min) over the duration of each experiment to prevent a rise in endogenous insulin secretion. After a baseline period of 2 h the trial drug (6, 12, or 24 U of either Insulin Aspart or regular human insulin in random order) are administered s.c. with a syringe into the abdominal wall. Glucose infusion rates (GIR) necessary to keep blood glucose concentrations close to the clamp level of 90 mg/dl (5 mmol/l) are administered and recorded by the Biostator every minute for a period of 12 h post-dosing. Blood samples are drawn at regular intervals for the analysis of C-peptide and (depending on the trial drug administered) serum insulin or serum Insulin Aspart concentrations (measured with specific ELISAs).

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Signed informed consent obtained before any trial-related activities
• Healthy subjects between 18 and 45 years inclusive
• Considered generally healthy upon completion of medical history and physical examination
• Body mass index (BMI) < 27 kg/m2
• HbA1c < 6,1 %
• Non-smoker for at least three months
• Females of childbearing potential using acceptable methods of contraception, including tubal ligation, an intrauterine device (IUD), the oral contraceptive pill or barrier methods.

Exclusion Criteria:

• Participation in any other clinical trial and receipt of any investigational drug within four weeks prior to this trial
• Previous participation in this trial
• Clinically significant abnormal haematology or biochemistry screening test
• Any disease requiring use of non topical prescription medicines
• Any serious systemic infectious disease that occurred in the four weeks prior to the first dose of test drug
• Any intercurrent illness that may affect blood glucose
• Current addiction to alcohol or substances of abuse as determined by the investigator
• Known or suspected allergy against insulin or any component of the composition of the trial drug
• Blood donation > 500 ml within the last nine weeks
• Mental incapacity, unwillingness or language barriers precluding adequate understanding or co-operation
• If female, subject is pregnant or lactating

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; 6 U insulin aspart	Drug: insulin aspart; 6, 12, 24 U s.c.; Other Names: Novorapid
Experimental: 2; 12 U insulin aspart	Drug: insulin aspart; 6, 12, 24 U s.c.; Other Names: Novorapid
Experimental: 3; 24 U insulin aspart	Drug: insulin aspart; 6, 12, 24 U s.c.; Other Names: Novorapid
Active Comparator: 4; 6 IU human regular insulin	Drug: human regular insulin; 6, 12 and 24 IU sc; Other Names: Actrapid
Active Comparator: 5; 12 IU human regular insulin	Drug: human regular insulin; 6, 12 and 24 IU sc; Other Names: Actrapid
Active Comparator: 6; 24 IU human regular insulin	Drug: human regular insulin; 6, 12 and 24 IU sc; Other Names: Actrapid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AUC GIR 360-720 min	at each dosing (6 times during the trial)

Secondary Outcome Measures

Outcome Measure	Time Frame
PK endpoints such as C max/ins, t max/ins, AUC ins 0-120 min, AUC ins 360-720 min, AUC ins 0-720 min	at each dosing visit (6 times during the study)
PD endpoints like GIR max, t max/GIR, AUC GIR 0-120 min, AUC GIR 0-720 min, t >2/GIR, early and late t 50%/GIR	at each dosing visit (6 times during the study)

Collaborators and Investigators

• Sponsor: Profil Institut für Stoffwechselforschung GmbH
• Collaborators: Novo Nordisk A/S

Publications and helpful links

Helpful Links

• Profil Institut für Stoffwechselforschung

Study record dates

Study Major Dates

• Study Start: April 1, 2002
• Study Completion (Actual): June 1, 2002

Study Registration Dates

• First Submitted: August 8, 2007
• First Submitted That Met QC Criteria: August 8, 2007
• First Posted (Estimate): August 9, 2007

Study Record Updates

• Last Update Posted (Estimate): August 9, 2007
• Last Update Submitted That Met QC Criteria: August 8, 2007
• Last Verified: August 1, 2007

More Information

Terms related to this study

• Keywords: hypoglycaemia; duration of action; euglycaemic glucose clamp; late metabolic activity
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Aspart
• Other Study ID Numbers: ISPS_Dose-ranging