Safety and Tolerability of Liraglutide in Healthy Volunteers and Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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This trial is conducted in Europe. The aim of this trial is to assess the safety and tolerability (maximum tolerated dose) after single and multiple doses of NNC 90-1170 (liraglutide) in healthy volunteers and in subjects with type 2 diabetes.

Official Title
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A Randomised, Double-blind, Placebo-controlled, Dose-escalation, Parallel-group, Single and Multiple Dosing Trial of NN90-1170 in Healthy Volunteers and Patients With Type 2 Diabetes to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics

Conditions
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Healthy, Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: liraglutide
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HEALTHY VOLUNTEERS Healthy subjects aged 18-45 years inclusive Healthy subjects are defined as individuals free from significant cardiac, pulmonary, gastrointestinal, hepatic, renal, haematological, neurological and psychiatric disease as determined by history, physical examination and clinical laboratory test results Women who are not of childbearing potential Signed and dated written informed consent obtained Body mass index (BMI) within the range 19-30 kg/m^2, inclusive SUBJECTS WITH DIABETES Subjects aged 40-70 years inclusive Subjects diagnosed with type-2 diabetes and a duration of diabetes of more than 12 months Women who are not of childbearing potential Signed and dated written informed consent obtained Fasting C-peptide at least 0.3 nmol/l and blood glucose at least 7 mmol/l Subjects currently on diet and/or OHA (oral hypoglycemic agents) for at least six months Body mass index (BMI) below 35 kg/m^2 HbA1c (glycosylated haemoglobin) below 11% Stable on current medication for at least 3 weeks prior to dosing in this study Exclusion Criteria: HEALTHY VOLUNTEERS Clinically relevant abnormal history or physical findings (e.g. cancer) at the screening assessment, which could interfere with the objectives of the study or the safety of the subject's participation Clinically relevant abnormalities of laboratory values or ECG at the screening evaluation Presence of acute or chronic illness sufficient to invalidate the subject's participation in the study or to make it unnecessarily hazardous Blood pressure and heart rate in seated position at the screening examination outside the ranges 90-150 mmHg systolic, 40-90 mmHg diastolic: heart rate 40-100 beats/min History of drug or alcohol abuse (alcohol abuse is defined as intake of more than 28 units weekly in men and more than 21 units weekly in women) Alcohol intake within 48 hours prior to visit Evidence of drug abuse on urine testing at study entry The subject smokes 10 cigarettes or more, or the equivalent, per day and is unable to refrain from smoking during 3 days prior to the first dosing day and during the confinement period Hepatitis B surface antigen (HBsAg), Hepatitis C antibodies or HIV (human immunodeficiency virus) antibodies History of significant drug allergy or drug hypersensitivity SUBJECTS WITH DIABETES Use of any drug (except for oral hypoglycaemic agents (OHAs)) which in the Investigator's opinion could interfere with the blood glucose level (e.g. insulin, systemic corticosteroids, thiazides) Recurrent severe hypoglycaemia as judged by the Investigator Clinically relevant abnormal history or physical findings (e.g. cancer) at the screening assessment, which could interfere with the objectives of the study or the safety of the subject's participation Clinically relevant abnormalities of laboratory values or ECG at the screening evaluation Presence of acute or chronic illness sufficient to invalidate the subject's participation in the study or to make it unnecessarily hazardous Blood pressure and heart rate in seated position at the screening examination outside the ranges 110-160 mmHg systolic, 60-90 mmHg diastolic: heart rate 40-100 beats/min History of drug or alcohol abuse (alcohol abuse is defined as intake of more than 28 units weekly in men and more than 21 units weekly in women) Alcohol intake within 48 hours of visit Evidence of drug abuse on urine testing at study entry The subject smokes 10 cigarettes or more, or the equivalent, per day and is unable to refrain from smoking during 3 days prior to the first dosing day and during the confinement period Hepatitis B surface antigen (HBsAg), Hepatitis C antibodies History of significant drug allergy or drug hypersensitivity

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NNC 90-1170<br> | Drug: liraglutide<br>* Initial single dose followed by subsequent multiple s.c. (under the skin) doses on several dose levels (1.25, 5, 7.5, 10 and 12.5 mcg/kg). Each subject will be allocated to one dose level only<br>* Other names: NNC 90-1170;|
| Placebo Comparator: Placebo<br> | Drug: placebo<br>* Initial single dose followed by subsequent multiple s.c. (under the skin) doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the Curve |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax, maximum concentration |  |  | 
| tmax, time to maximum concentration |  |  | 
| t½, terminal half-life |  |  | 
| Adverse events |  |  |