Clinical trial NCT00513643: Metabolic Effect of Insulin Aspart and Human Insulin in Different Doses
Official title: Pharmacodynamic and Pharmacokinetic Properties of Insulin Aspart: Dose - Ranging vs. Human Soluble Insulin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus
Keywords: euglycaemic glucose clamp
duration of action
late metabolic activity
hypoglycaemia
Lead sponsor: Profil Institut für Stoffwechselforschung GmbH
Sponsor class: INDUSTRY
Collaborators: name: Novo Nordisk A/S
First posted: 2007-08-09
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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

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).

Eligibility criteria: 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

Primary outcomes:
measure: AUC GIR 360-720 min
timeFrame: at each dosing (6 times during the trial)
Secondary outcomes:
measure: 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
timeFrame: at each dosing visit (6 times during the study)
measure: 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
timeFrame: at each dosing visit (6 times during the study)
Other outcomes:
Locations:
city: Neuss
country: Germany
facility: Profil Institut für Stoffwechselforschung GmbH
Study officials:
affiliation: Profil Institut für Stoffwechselforschung GmbH
name: Tim Heise, MD
role: PRINCIPAL_INVESTIGATOR
References: