A Randomised, Single Centre, Double-Blind, Two-Period Crossover, Glucose Clamp Trial (ENM-HS-001)
Clinical pharmacology trials investigating insulin detemir in subjects with type 1 diabetes have shown a prolonged and reproducible action profile of insulin detemir compared with NPH insulin and insulin glargine. Duration of action of insulin detemir has been reported to be up to 24 hours.9,10,11 It has, however, been proposed that the mean duration of action is underestimated in glucose clamps lasting only 24 hours. This is so because a duration of action longer than 24 hours in individual clamps will be set to 24 hours in the mean calculation, whereas a shorter duration of action in individual clamps will be set to the true value.
It has been shown in clinical pharmacology trials that NPL insulin has an action profile comparable to NPH insulin in subjects with type 1 diabetes. , However, a direct comparison of pharmacodynamic properties of insulin detemir and NPL insulin has not been performed to date.
To get further insight into the pharmacodynamic properties of insulin detemir compared with NPL insulin, this trial has been designed to compare pharmacodynamics in general and duration of action in particular between insulin detemir and NPL insulin in subjects with type 1 diabetes.
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||A Randomised, Single Centre, Double-Blind, Two-Period Crossover, Glucose Clamp Trial to Compare the Pharmacodynamic Effects of Single Doses of Insulin Detemir and Neutral Protamin Lispro (NPL) Insulin in Subjects With Type 1 Diabetes|
- Duration of action, time from onset of action until end of action [ Time Frame: 32 h ] [ Designated as safety issue: No ]
- GIRmax, maximum glucose infusion AUCGIR,0-32h, AUCGIR,0-12h, AUCGIR,12-32h, tinf=0, Cmax,ins, tmax,ins, AUCins,0-24h AUCins,0-∞ AUCins,0-12h AUCins,12-24h [ Time Frame: 0-32 h, 0-12 h, 0-24 h ] [ Designated as safety issue: Yes ]
|Study Start Date:||November 2008|
|Study Completion Date:||December 2008|
|Primary Completion Date:||December 2008 (Final data collection date for primary outcome measure)|
0,4 IE per kg bodyweight
Other Name: Insulin Detemir
|Active Comparator: 2||
Drug: Humalog NPL Insulin
0,4 IE per kg bodyweight
Other Name: Humalog NPL
The primary objective is to compare the pharmacodynamic response of insulin detemir and NPL insulin with respect to duration of action in a 32-hour euglycaemic glucose clamp experiment following single dose administration in subjects with type 1 diabetes.
The secondary objectives are:
- to additionally characterise the pharmacodynamic profiles of insulin detemir and NPL insulin in a 32-hour euglycaemic glucose clamp experiment following single dose administration in subjects with type 1 diabetes.
- to characterise the pharmacokinetic profiles of insulin detemir and NPL insulin following single dose administration in subjects with type 1 diabetes.
- to assess the safety and tolerability of insulin detemir and NPL insulin following single dose administration in subjects with type 1 diabetes.
This is a randomised, single centre, double-blind, two-period crossover trial. Each subject will be randomly allocated to two single dose administrations on two separate dosing visits.
Thirty (30) male and female subjects with type 1 diabetes [age 18-65 years (incl.) and body mass index between 18.0 and 32.0 kg/m2 (incl.)] will be randomised into the trial.
Pharmacodynamics: The glucose infusion rate and plasma glucose concentration will be measured during a euglycaemic glucose clamp running for 32 hours after dosing.
Pharmacokinetics: Serum concentrations of insulin detemir and insulin lispro will be measured frequently during the first 32 hours after dosing.
Safety: Adverse events, laboratory safety variables (haematology, biochemistry, urinalysis), physical examination, vital signs and hypoglycaemic episodes.
- Insulin detemir (Levemir® Novo Nordisk), 100 U/mL in 3 mL Penfill® cartridges
- Insulin lispro protamine suspension (Humalog® NPL, Eli Lilly), 100 U/mL in 3 mL cartridges
|Medical University Graz|
|Graz, Austria, 8036|
|Study Director:||Thomas R. Pieber, MD||Medical University Graz, Internal Medicine, Endocrinology and Nuclear Medicine|