A Trial Investigating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Subcutaneous NNC0123-0338 in Healthy Subjects and in Subjects With Type 1 Diabetes Mellitus

This trial is conducted in Europe. The purpose is to evaluate safety and tolerability of a range of single doses of subcutaneous insulin 338.

Study Overview

• Status: Completed
• Conditions: Healthy; Diabetes; Diabetes Mellitus, Type 1
• Intervention / Treatment: Drug: Insulin 338; Drug: Insulin 338; Drug: placebo; Drug: insulin glargine

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Neuss, Germany, 41460
    • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Trial Part 1 (Healthy subjects):
• Male subject
• Age 18-55 (both inclusive) at the time of signing inform consent
• Body mass index 19.0-29.9 kg/m^2 (both inclusive)
• Trial Part 2 (Subjects with type 1 diabetes mellitus):
• Male subject or female subject of non-child bearing potential. Non-child bearing potential: being surgically sterilized (i.e. tubal ligation, bilateral oopherectomies or hysterectomised) for more than 3 months or being postmenopausal (as defined by amenorrhoea for at least 2 years prior to screening and documented by follicle-stimulating hormone (FSH) 40 U/L)
• Age 18-64 years (both inclusive) at the time of signing inform consent
• Body mass index 19.0-29.9 kg/m^2 (both inclusive)
• Type 1 diabetes mellitus (as diagnosed clinically) for 12 months or longer
• Treated with multiple daily insulin injections or insulin pump treatment for 12 months or longer
• Glycated hemoglobin (HbA1c) 9.0% or less
• Fasting C-peptide less than 0.3 nmol/L

Exclusion Criteria:

• Trial Part 1 (healthy subjects):
• History of, or presence of, cancer, diabetes mellitus or any clinically significant cardiovascular, respiratory, metabolic (including dyslipidemia), renal, hepatic, gastrointestinal, endocrinological, haematological, dermatological, venereal, neurological, psychiatric diseases or other major disorders, as judged by the investigator
• Increased risk of thrombosis, e.g. subjects with a history of deep leg vein thrombosis or family history of deep leg vein thrombosis, as judged by the investigator
• Currently smoke more than 1 cigarette per day (or the equivalent for other tobacco products) or smoking 1 cigarette or less per day and not considering being able to refrain from smoking or refrain from use of other types of nicotine products (e.g. such as chewing tobacco, nicotine gums) during the in-house periods
• Trial Part 2 (subjects with type 1 diabetes mellitus):
• History of, or presence of, cancer or any clinically significant respiratory, metabolic, renal, hepatic, gastrointestinal, endocrinological (with the exception of conditions associated with diabetes mellitus), haematological, dermatological, venereal, neurological, psychiatric, other major disorders or personal and/or family history of thromboembolism, as judged by the investigator
• Increased risk of thrombosis, e.g. subjects with a history of deep leg vein thrombosis or family history of deep leg vein thrombosis, as judged by the investigator
• Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic event during the last 12 months) or hypoglycaemic unawareness as judged by the Investigator or hospitalisation for diabetic ketoacidosis during the past 6 months before start of this trial (screening)
• Cardiac problems defined as: 1) decompensated heart failure (New York Heart Association (NYHA) class III and IV) at any time, or 2) acute myocardial infarction at any time, or 3) angina pectoris within the last 12 months before start of this trial (screening)
• Currently smoke more than 1 cigarette per day (or the equivalent for other tobacco products) or smoking 1 cigarette or less per day and not considering being able to refrain from smoking or refrain from use of other types of nicotine products (e.g. such as chewing tobacco, nicotine gums) during the in-house periods.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 insulin 338	Drug: Insulin 338; Healthy subjects will receive a single dose of insulin 338 in ascending doses. Injected subcutaneously (under the skin).; Drug: Insulin 338; Subjects with type 1 DM will receive a single dose of insulin 338 in ascending doses. Injected subcutaneously (under the skin).
Placebo Comparator: Part 1 placebo	Drug: placebo; Healthy subjects will receive a single dose of placebo. Injected subcutaneously (under the skin).
Experimental: Part 2 insulin 338	Drug: Insulin 338; Healthy subjects will receive a single dose of insulin 338 in ascending doses. Injected subcutaneously (under the skin).; Drug: Insulin 338; Subjects with type 1 DM will receive a single dose of insulin 338 in ascending doses. Injected subcutaneously (under the skin).
Active Comparator: Part 2 insulin glargine	Drug: insulin glargine; Subjects with type 1 DM will receive 0.4 U/kg insulin glargine once daily for 4 days. Injected subcutaneously (under the skin).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of adverse events	Day 1 - day 22

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of hypoglycaemic episodes	Day 1 - day 22
Area under the serum insulin 338 concentration-time curve from zero to infinity	Day 1- day 22
Maximum serum insulin 338 concentration observed	Day 1- day 22
Time for maximum serum insulin 338 concentration	Day 1- day 22
t1/2, the terminal half-life of insulin 338	Day 1- day 22

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 (Actual): August 20, 2014
• Primary Completion (Actual): March 31, 2015
• Study Completion (Actual): March 31, 2015

Study Registration Dates

• First Submitted: August 18, 2014
• First Submitted That Met QC Criteria: August 18, 2014
• First Posted (Estimate): August 19, 2014

Study Record Updates

• Last Update Posted (Actual): December 8, 2017
• Last Update Submitted That Met QC Criteria: December 6, 2017
• Last Verified: December 1, 2017

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 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Glargine
• Other Study ID Numbers: NN1438-4137; 2014-000071-70 (EudraCT Number); U1111-1151-9327 (Other Identifier: WHO)