Clinical trial NCT00888732: A Comparison of Pharmacodynamics and Pharmacokinetics of Insulin Aspart, BIAsp70, BIAsp50 and Fast-acting Human Insulin
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 1
Keywords: Diabetes
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Novo Nordisk A/S
First posted: 2009-04-28
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: 12 hours following a standard test meal (breakfast)
Secondary outcomes:
measure: 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
timeFrame: 12 hours following a standard test meal (breakfast)
measure: 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
timeFrame: 12 hours following a standard test meal (breakfast)
measure: tmaxins: Time to maximum serum insulin aspart/human insulin concentration
timeFrame: 12 hours following a standard test meal (breakfast)
measure: 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)
timeFrame: 12 hours following a standard test meal (breakfast)
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Dept of Medicine M, Aarhus University Hospital
Study officials:
affiliation: University of Aarhus
name: Jens S Christiansen, M.D
role: PRINCIPAL_INVESTIGATOR
References:
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.
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. doi: 10.2337/diacare.20.10.1612.
citation: Kang S, Creagh FM, Peters JR, Brange J, Volund 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. doi: 10.2337/diacare.14.7.571.
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. doi: 10.1089/152091599316775.
citation: Jacobsen LV, Sogaard 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. doi: 10.1007/s002280000159.
citation: Ma Z, Christiansen JS, Laursen T, Wu C, Lauritzen T, Parkner T, Frystyk J. Effects of human insulin and insulin aspart preparations on levels of IGF-I, IGFBPs and IGF bioactivity in patients with type 1 diabetes. BMC Endocr Disord. 2014 Apr 11;14:35. doi: 10.1186/1472-6823-14-35.
citation: Ma Z, Parkner T, Frystyk J, Laursen T, Lauritzen T, Christiansen JS. A comparison of pharmacokinetics and pharmacodynamics of insulin aspart, biphasic insulin aspart 70, biphasic insulin aspart 50, and human insulin: a randomized, quadruple crossover study. Diabetes Technol Ther. 2012 Jul;14(7):589-95. doi: 10.1089/dia.2011.0299. Epub 2012 Apr 20.