Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Explorative Formulation of Insulin Degludec

Study Overview
=================
Brief Summary
-----------------
This trial is conducted in Europe. The aim of this trial is to investigate the safety, tolerability, pharmacokinetics (the exposure of the trial drug in the body) and pharmacodynamics (the effect of the investigated drug on the body) of insulin degludec (insulin 454), an explorative formulation, not similar to the proposed commerical formulation.

Official Title
-----------------
A Randomised, Double-blind, Placebo-controlled Single Dose, Dose Escalation Trial With Insulin 454 in Healthy Male Subjects, Followed by a Two-period Cross-over Trial With Insulin 454 and Insulatard® in Male Subjects With Type 1 and Type 2 Diabetes Mellitus

Conditions
-----------------
Diabetes, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2

Intervention / Treatment
-----------------
* Drug: insulin degludec
* Drug: placebo
* Drug: insulin degludec
* Drug: isophane human insulin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: HEALTHY SUBJECTS: Subjects will be healthy male subjects, who are considered to be generally healthy based on an assessment of medical history, physical examination and clinical laboratory data, as judged by the Investigator Body mass index (BMI) between 18.0-27.0 kg/m^2 (both inclusive) SUBJECTS WITH TYPE 1 AND TYPE 2 DIABETES: Subjects will be male volunteers, who are considered to be generally healthy, except for the underlying diabetes mellitus, based on an assessment of medical history, physical examination and clinical laboratory data, as judged by the Investigator Diagnosed with type 1 diabetes mellitus and treated with insulin for at least 12 months or diagnosed with type 2 diabetes mellitus for at least 12 months Body Mass Index (BMI) between 18.0-27.0 kg/m^2 (both inclusive) for subjects with type 1 diabetes or 25.0-35.0 kg/m^2 (both inclusive) for subjects with type 2 diabetes Glycogylated haemoglobin (HbA1c) maximum 8.5 % based on central laboratory results Subjects with type 2 diabetes must have been treated with insulin for the past 3 months prior to screening Exclusion Criteria: Participation in any other trials involving investigational products within 3 months preceding the start of dosing History of significant multiple drug allergies or with a known allergy to the trial product or any medicine chemically related to the trial product, as judged by the investigator Hepatitis or carrier of the Hepatitis B surface antigen (HBsAg) or Hepatitis C antibodies or a positive result to the test for human immunodeficiency (HIV) antibodies Any clinically significant abnormal haematology or biochemistry screening tests, as judged by the investigator Subjects who have donated any blood or plasma in the past month or in excess of 1000 ml within the 12 weeks preceding screening

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trial part 1<br> | Drug: insulin degludec<br>* Ascending single doses - 5 dose levels. Escalation to next dose level will be performed following evaluation of safety data.<br>Drug: placebo<br>* Ascending single doses - 5 dose levels<br>|
| Active Comparator: Trial part 2<br> | Drug: insulin degludec<br>* A single dose corresponding to that of isophane human insulin<br>Drug: isophane human insulin<br>* A single dose of 0.4 IU/kg is administered to subjects with type 1 diabetes while a single dose of 0.6 IU/kg is administered to subjects with type 2 diabetes<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of adverse events (trial part 1 only) |  | From day prior to dosing and until 10-14 days after dosing | 
| Area under the glucose infusion rate curve (trial part 2 only) |  | 0-24 hours after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the serum insulin concentration curve |  | 0-72 hours after dosing |