A Comparison of Pharmacodynamics and Pharmacokinetics of Insulin Aspart, BIAsp70, BIAsp50 and Fast-acting Human Insulin

Diabetes Mellitus, Type 1 Clinical Trial

Official title:

A Comparison of Pharmacodynamics and Pharmacokinetics of Insulin Aspart, Biphasic Insulin Aspart 70 and 50 & Fast-acting Human Insulin in Patients With Type 1 Diabetes, A Randomised, Quadruple Crossover Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00888732
• Other study ID #: Asp-BIAsp-HI-2008
• Secondary ID: 2008-007176-22
• Status: Completed
• Phase: Phase 3
• First received: April 27, 2009
• Last updated: April 27, 2011
• Start date: June 2009
• Est. completion date: June 2010

Study information

• Verified date: April 2011
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Medicines AgencyDenmark: Danish Dataprotection Agency
• Study type: Interventional

Clinical Trial Summary

The hypothesis is that an optimal formulation of fast acting and intermediary acting insulin analogues will improve post prandial glycaemic control in patients with type 1 diabetes

Description:

This trial is a single centre, open-label, randomised 4 period cross-over trial, comparing the pk and pd profiles of IAsp, BIAsp 50, BIAsp 70 and Fast-acting Human Insulin after a standard test meal in subjects with type 1 diabetes. The profiles will be derived over a 12-hour period after subcutaneous injection in the abdominal region with a single dose of IAsp, BIAsp 50, BIAsp 70 or Fast-acting Human Insulin at a test meal. The trial consists of a screening period of 4-21 days and 4 treatment visits.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: June 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Informed consent obtained before any trial-related activities.

• Diagnosed type 1 diabetes before the age of 40 and on insulin treatment within one year of diagnosis.

• Insulin treatment of any regime for more than one year at time of inclusion.

• Total insulin demand = 0,4 U/IU/kg/24 hrs

• HbA1c between 7% and 12% (both values included).

• Age = 18 years.

• BMI between 18 and 35 kg /m2 (including both values).

Exclusion Criteria:

• Known or suspected allergy to trial product(s) or related products.

• Recurrent major hypoglycaemic episodes.

• Heart: Unstable Angina Pectoris, AMI < 12 months or heart insufficiency classified according to NYHA III-IV

• Blood Pressure: Severe uncontrolled hypertension with BP > 180/110 mmHg, sitting

• Liver: Impaired hepatic function corresponding to serum-ALAT or basic phosphatase > 2 x upper reference limit of the local laboratory.

• Kidneys: Impaired renal function corresponding to serum-creatinin > 150 µmol/l according to the local laboratory.

• Any disease judged by the investigator to affect the trial.

• Pregnancy, breast-feeding or the intention of becoming pregnant or fertile women not using adequate contraceptive measures - adequate contraceptive method is sterilisation, hysterectomy or current use of contraceptive pills or intra uterine device.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1

Intervention

Drug:
• Insulin Aspart, BIAsp 70, BIAsp50, Human Insulin
0.2 U/IU/kg subcutaneous injection, single dose

Locations

Country	Name	City	State
Denmark	Dept of Medicine M, Aarhus University Hospital	Aarhus

Sponsors (2)

Lead Sponsor	Collaborator
University of Aarhus	Novo Nordisk A/S

Country where clinical trial is conducted

Denmark, 

References & Publications (5)

Jacobsen LV, Søgaard B, Riis A. Pharmacokinetics and pharmacodynamics of a premixed formulation of soluble and protamine-retarded insulin aspart. Eur J Clin Pharmacol. 2000 Aug;56(5):399-403. — View Citation

Kang S, Creagh FM, Peters JR, Brange J, Vølund A, Owens DR. Comparison of subcutaneous soluble human insulin and insulin analogues (AspB9, GluB27; AspB10; AspB28) on meal-related plasma glucose excursions in type I diabetic subjects. Diabetes Care. 1991 Jul;14(7):571-7. — View Citation

Thorisdottir RL, Parkner T, Chen JW, Ejskjaer N, Christiansen JS. A comparison of pharmacokinetics and pharmacodynamics of biphasic insulin aspart 30, 50, 70 and pure insulin aspart: a randomized, quadruple crossover study. Basic Clin Pharmacol Toxicol. 2009 Mar;104(3):216-21. doi: 10.1111/j.1742-7843.2008.00355.x. Epub 2009 Jan 20. — View Citation

Thrailkill KM. Insulin-like growth factor-I in diabetes mellitus: its physiology, metabolic effects, and potential clinical utility. Diabetes Technol Ther. 2000 Spring;2(1):69-80. Review. — View Citation

Weyer C, Heise T, Heinemann L. Insulin aspart in a 30/70 premixed formulation. Pharmacodynamic properties of a rapid-acting insulin analog in stable mixture. Diabetes Care. 1997 Oct;20(10):1612-4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cmaxglu: Peak plasma glucose following test meal (breakfast). A comparison will be made between fast-acting human insulin vs. IAsp, BIAsp 50 and BIAsp 70, IAsp vs BIAsp 50 and BIAsp 70, BIAsp 50 vs. BIAsp 70.		12 hours following a standard test meal (breakfast)	No
Secondary	AUCglu: The area under the plasma glucose concentration (0-12, 0-6, 6-12, 0-4, 4-8, 8-12 hours after test meal) after a single injection of one of the four insulins: IAsp, Biphasic insulin aspart 50 and 70 & fast-acting human insulin		12 hours following a standard test meal (breakfast)	No
Secondary	AUCins: The area under insulin aspart/human insulin concentration (0-12, 0-6, 6-12, 0-4, 4-8, 8-12 hours after test meal) after a single injection of one of the four insulins: IAsp, Biphasic insulin aspart 50 and 70 & fast-acting human insulin		12 hours following a standard test meal (breakfast)	No
Secondary	tmaxins: Time to maximum serum insulin aspart/human insulin concentration		12 hours following a standard test meal (breakfast)	No
Secondary	Serum GH, total IGF-I, IGF-I bioactivity, IGFBP-1, IGFBP-2, binary complex of IGF-I, IGFBP-3 and the acid-labile subunit (ALS)		12 hours following a standard test meal (breakfast)	No

External Links

•   Click here for more information about trial site (Danish version only)