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

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Diabetes; Diabetes Mellitus, Type 1
• Intervention / Treatment: Drug: insulin degludec; Drug: placebo; Drug: insulin degludec; Drug: isophane human insulin

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Neuss, Germany, 41460

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Trial part 1	Drug: insulin degludec; Ascending single doses - 5 dose levels. Escalation to next dose level will be performed following evaluation of safety data.; Drug: placebo; Ascending single doses - 5 dose levels; Drug: insulin degludec; A single dose corresponding to that of isophane human insulin
Active Comparator: Trial part 2	Drug: insulin degludec; Ascending single doses - 5 dose levels. Escalation to next dose level will be performed following evaluation of safety data.; Drug: insulin degludec; A single dose corresponding to that of isophane human insulin; Drug: isophane human insulin; 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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start: December 1, 2005
• Primary Completion (Actual): April 1, 2006
• Study Completion (Actual): April 1, 2006

Study Registration Dates

• First Submitted: May 27, 2013
• First Submitted That Met QC Criteria: May 27, 2013
• First Posted (Estimate): May 30, 2013

Study Record Updates

• Last Update Posted (Estimate): October 23, 2015
• Last Update Submitted That Met QC Criteria: October 22, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin, Long-Acting; Insulin, Isophane; Isophane Insulin, Human; Isophane insulin, beef
• Other Study ID Numbers: NN5401-1718; 2005-003974-65 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No