Clinical trial NCT01730014: A Trial Investigating the Safety, Tolerability, and Distribution and Activity in the Body of NNC0148-0000-0287 Injected Under the Skin in Healthy Subjects and in Subjects With Type 1 Diabetes
Official title: A Trial Investigating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Subcutaneous NNC0148-0000-0287 in Healthy Subjects and in Subjects With Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes
Diabetes Mellitus, Type 1
Healthy
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2012-11-21
Enrollment: 70
Sex: MALE
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This trial is conducted in Europe. The aim of this trial is to investigate safety, tolerability, pharmacokinetics (the exposure of the trial drug in the body) and pharmacodynamics (the effect of the investigated drug on the body) of subcutaneous NNC0148-0000-0287 (insulin 287) in healthy subjects and in subjects with type 1 diabetes


Eligibility criteria: Inclusion Criteria:

* TRIAL PART 1 (HEALTHY SUBJECTS):
* Healthy male subject
* Age 18-55 years (both inclusive)
* Body mass index 18.0-28.0 kg/m\^2 (both inclusive)
* TRIAL PART 2 (SUBJECTS WITH TYPE 1 DIABETES):
* Healthy male subject (with the exception of conditions associated with diabetes mellitus)
* Age 18-64 years (both inclusive)
* Body mass index 18.0-28.0 kg/m\^2 (both incl.)
* Type 1 diabetes mellitus (as diagnosed clinically) and treated with multiple daily insulin injections more than 12 months
* HbA1C (glycosylated haemoglobin) below or equal to 8.5 %
* Current daily basal insulin requirement above or equal to 0.2 to below or equal to 0.8 (I)U/kg/day and current total daily insulin treatment below 1.2 (I)U/kg/day
* Fasting C-peptide below 0.3 nmol/L

Exclusion Criteria:

* The receipt of any investigational medicinal product within the last 3 months prior to the start of this trial (screening)
* Significant blood loss (due to donation, surgery or trauma) of more than 500 mL within 3 months prior to the start of this trial (screening) or participating in any other trial involving blood sampling within the last 2 months before the start of this trial (screening)
* Use of any prescription (see specification below for Trial Part 2) or non-prescription medication, including herbal products and non-routine vitamins, within the last 2 weeks before the start of the trial (screening) that will interfere with the pharmacokinetics of insulin 287, as judged by the investigator in agreement with the sponsor. Routine vitamins and occasional use judged by the investigator in agreement with the sponsor. Routine vitamins and occasional use of paracetamol is permitted up to 48 hours prior to dosing
* History of alcoholism or drug abuse (within the last 2 years), or positive result of alcohol or drug screening test
* 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
* Habitual excessive consumption of methylxanthine-containing (theophylline, caffeine or theobromine) beverages and foods (coffee, tea, soft drinks such as red bull, cola, chocolate) as judged by the investigator
* Excessive consumption of a diet deviating from a normal diet as judged by the investigator
* Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation in the trial
* Vulnerable subjects (e.g. persons kept in detention)
* Subject is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the trial
* ADDITIONAL KEY EXCLUSION CRITERIA TRIAL PART 2 (subjects with type 1 diabetes):
* Current treatment with statins, systemic (oral, intravenous or inhaled) corticosteroids, monoamine oxidase (MAO) inhibitors, non-selective beta-blockers, thyroid hormones, growth hormone and other drugs, which may interfere with glucose metabolism
* 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: decompensated heart failure (New York Heart Association (NYHA) class III and IV) at any time, or acute myocardial infarction at any time, or angina pectoris within the last 12 months before start of this trial (screening)
* Proliferative retinopathy or maculopathy and/or severe neuropathy, in particular autonomic neuropathy, as judged by the investigator

Primary outcomes:
measure: Incidence of adverse events (AE)
timeFrame: From trial product administration until completion of the post-treatment follow-up visit at Day 37
Secondary outcomes:
measure: Incidence of hypoglycaemic episodes
timeFrame: From trial product administration until completion of the post-treatment follow-up visit at Day 37
measure: AUC, the area under the serum insulin 287 concentration-time curve
timeFrame: From dosing visit to infinity calculated from a 0-36 days NNC0148-0287 serum concentration-time-curve based on 43 sampling time points
measure: Cmax, the maximum serum insulin 287 concentration
timeFrame: Observed (within 0-36 days)
measure: tmax, the time for maximum serum insulin 287 concentration
timeFrame: Within 0-36 days
measure: Average morning fasting blood glucose (FBG) concentration
timeFrame: From Day 2 to Day 8
measure: Average morning fasting serum C-peptide concentration
timeFrame: From Day 2 to Day 8
measure: Average morning fasting serum free fatty acid (FFA) concentration
timeFrame: From Day 2 to Day 8
measure: Area under the glucose infusion rate (GIR)-time curve
timeFrame: At Day 1-2, 4-5, or 7-8
measure: The maximal GIR (glucose infusion rate) observed
timeFrame: At Day 1-2, 4-5, or 7-8
Other outcomes:
Locations:
city: Neuss
country: Germany
Study officials:
affiliation: Novo Nordisk A/S
name: Global Clinical Registry (GCR, 1452)
role: STUDY_DIRECTOR
References: