A Randomised, Single Centre, Double-Blind, Two-Period Crossover, Glucose Clamp Trial
Condition: Diabetes, Type I
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      Primary objective:

      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.

      Secondary objectives:

      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.

      Trial design:

      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.

      Trial population:

      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.

      Assessments:

      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.

      Trial products:

        -  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
    

Intervention name(s): Levemir; Humalog NPL Insulin
Intervention type(s): Drug; Drug
Intervention description(s): 0,4 IE per kg bodyweight; 0,4 IE per kg bodyweight
Other intervention name(s): Insulin Detemir; Humalog NPL
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Insulin Lispro; Insulin Detemir
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment