A Randomised, Single Centre, Double-Blind, Two-Period Crossover, Glucose Clamp Trial

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

Inclusion criteria

• Informed consent obtained before any trial-related activities.
• Diagnosed with type 1 diabetes and treated with insulin
• Male or female subject between 18 and 65 years of age
• Body mass index between 18.0 and 32.0 kg/m2
• HbA1c (glycosylated haemoglobin A1c) ≤ 11%
• Fasting C-peptide ≤ 0.05 nmol/L
• Treatment with intensified insulin therapy or continuous subcutaneous human insulin or insulin analogue infusion (CSII)] for at least 3 months.

Exclusion criteria

• Known or suspected allergy to the trial products or related products,
• Previous participation (randomised) in this trial.
• The receipt of any investigational product within 3 months prior
• Clinically significant abnormal haematology or biochemistry screening tests
• Subject who is known to have hepatitis or who is a carrier of the Hepatitis B surface antigen (HBsAg) or Hepatitis C antibodies, or has a positive result to the test for HIV antibodies.
• Supine blood pressure at screening (after 5 min in the supine position) ≥ 180 mmHg for systolic and/or ≥ 100 mmHg for diastolic. This exclusion criterion also pertains to subjects being on antihypertensives.
• Clinically significant abnormal ECG at screening
• Subject who has donated blood in excess of 500 mL within the 9 weeks preceding screening.
• Significant history of alcoholism or drug/chemical abuse
• Smoker
• Subject with mental incapacity or language barriers
• Surgery or trauma with significant blood loss within the 9 weeks preceding screening.
• Subject with a history of or presence of cancer
• History of any illness or disease that, in the opinion of the Investigator might confound the results of the trial or pose additional risk in administering the trial product to the subject.
• Current systemic treatment with drugs that could interfere with glucose metabolism [such as systemic corticoids and monoamine oxidase (MAO) inhibitors] and/or pharmacokinetics.
• Subject who has proliferative retinopathy or maculopathy and/or severe neuropathy (in particular autonomic neuropathy)
• Any condition that would interfere with trial participation or evaluation of results, as judged by the Investigator and/or the sponsor.
• Female of childbearing potential who is pregnant, breast-feeding or intends to become pregnant or is not using adequate contraceptive methods