Safety, Tolerability and Pharmacokinetics of Liraglutide-depot in Healthy Subjects

Study Overview
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Brief Summary
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This trial is conducted in the United States of America (USA). The aim of this trial is to investigate the safety, tolerability and pharmacokinetics (exposure in the body) of liraglutide-depot in healthy subjects.

Official Title
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Investigation on Safety, Tolerability and Pharmacokinetics of Liraglutide-depot in Healthy Subjects. A Randomised, Double-blind, Placebo-controlled Trial Investigating Subcutaneously Single Dose Escalation of a Sustained Release Formulation of Liraglutide Lysine in Healthy Male Subjects

Conditions
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Diabetes, Diabetes Mellitus, Type 2, Healthy

Intervention / Treatment
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* Drug: liraglutide-depot
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index (BMI) between 20 and 35 kg/m^2 (both inclusive) with a body weight of at least 60 kg Apart from being obese (BMI above 30 kg/m^2) the subject has to be considered generally healthy Exclusion Criteria: Medical history of, or presence of, cancer, diabetes or any clinically significant cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal, endocrine, haematological, dermatological, venereal, neurological, psychiatric diseases or other major disorders Clinical or laboratory findings which suggest that the subject cannot be considered generally healthy Prescription medicine and non-prescription medicine with few exceptions Current and prior history of alcohol or drug abuse Current smoking of more than 5 cigarettes per day Mental incapacity, language barriers, or unwillingness to comply with the protocol

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

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

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: Cohort 1a: Lira-depot 2.25 mg<br> | Drug: liraglutide-depot<br>* Subjects will be randomised to receive a single dose of liraglutide-depot, at increasing dose levels, injected s.c./subcutaneously (under the skin). Progression to next dose level (max. 8) will be based on safety evaluation.<br>|
| Experimental: Cohort 2a: Lira-depot 6.75 mg<br> | Drug: liraglutide-depot<br>* Subjects will be randomised to receive a single dose of liraglutide-depot, at increasing dose levels, injected s.c./subcutaneously (under the skin). Progression to next dose level (max. 8) will be based on safety evaluation.<br>|
| Experimental: Cohort 3a: Lira-depot 15 mg<br> | Drug: liraglutide-depot<br>* Subjects will be randomised to receive a single dose of liraglutide-depot, at increasing dose levels, injected s.c./subcutaneously (under the skin). Progression to next dose level (max. 8) will be based on safety evaluation.<br>|
| Experimental: Cohort 4a: Lira-depot 30 mg<br> | Drug: liraglutide-depot<br>* Subjects will be randomised to receive a single dose of liraglutide-depot, at increasing dose levels, injected s.c./subcutaneously (under the skin). Progression to next dose level (max. 8) will be based on safety evaluation.<br>|
| Placebo Comparator: Placebo<br> | Drug: placebo<br>* Subjects will be randomised to receive a single dose of liraglutide-depot placebo, at increasing dose levels, injected s.c./subcutaneously (under the skin).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Treatment Emergent Adverse Events (TEAEs) | TEAEs: AEs from 1st exposure (exp) until follow-up (FU) or AEs with onset before 1st exp increasing in severity up to the FU. Mild AEs: no or transient symptoms, no interference (inf) with subject's daily activities. Moderate AEs: marked symptoms, moderate inf with subject's daily activities. Severe AEs: considerable inf with subject's daily activities, unacceptable. Serious AE: AE that at any dose results in death/ a life-threatening experience/ in-subject hospitalization/prolongation of existing hospitalisation; or persistent/significant disability/incapacity/congenital anomaly/birth defect. | Day 0 and up to 21 days after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration of Liraglutide After a Single Dose of Liraglutide-depot |  | Day 0 through day 21 at 1,3,6,12,18, 24, 36, 48, 72, 96, 120, 168, 336, 504 hours post dose | 
| Time to Maximum Plasma Concentration of Liraglutide After a Single Dose of Liraglutide-depot |  | Day 0 through day 21 at 1,3,6,12,18, 24, 36, 48, 72, 96, 120, 168, 336, 504 hours post dose | 
| Area Under the Plasma Concentration Curve in the Period From the Time of Liraglutide-depot Administration to Infinity |  | Day 0 through day 21 at 1,3,6,12,18, 24, 36, 48, 72, 96, 120, 168, 336, 504 hours post dose | 
| Area Under the Liraglutide Plasma Concentration Curve in the First Week Following Liraglutide-depot Administration for Subjects Without Liraglutide 6 mg/ml Pre-treatment |  | 1,3,6,12,18, 24, 36, 48, 72, 96, 120, 168 hours post dose | 
| Area Under the Plasma Concentration Curve in the First Week Following Liraglutide-depot Administration for Subjects With Liraglutide 6 mg/ml Pre-treatment |  | 0 to 168 hours after dosing | 
| Number of Subjects With Antibodies (Positive) or Without Antibodies (Negative) Against Liraglutide Observed at Pre-dose and at Last Follow-up |  | Day 0 and Day 21 |