Effect of Liraglutide on Heart Frequency in Healthy Volunteers

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 if liraglutide effects the QTc interval. Moxifloxacin (Avelox®) is administered as positive control.

Official Title
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A Thorough QTc Evaluation of the Effect of Liraglutide on Cardiac Repolarization in Healthy Volunteers: A Randomized, Double-blind, Placebo-controlled, Two Period Crossover Study Followed by Open-label Moxifloxacin (Positive Control) Administration

Conditions
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Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: liraglutide
* Drug: placebo
* Drug: moxifloxacin
* Drug: placebo
* Procedure: electrocardiogram (ECG)
* Procedure: electrocardiogram (ECG)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Fasting plasma glucose within normal limits (80-100 mg/dl) BMI (Body Mass Index): 20.0-29.0 kg/m^2 (inclusive) Heart rate within the range of 50-90 beats per minute (inclusive) Subject is judged to be in good health on the basis of their medical history, physical examination, ECG (electrocardiogram), and routine laboratory data Exclusion Criteria: Any clinically significant disease history, in the opinion of the investigator, of systemic or organ disease Any clinically significant disease history, in the opinion of the investigator, of cardiovascular disease Clinically significant abnormalities on any pre-study clinical examination or any abnormal laboratory measurements during screening A family history of sudden cardiac death at age less than 50 years old T-wave abnormalities Individual or familial history of long QT Syndrome Positive results on Screening for Hepatitis B surface antigen, Hepatitis C antibody or HIV (human immunodeficiency virus) antibody Positive results on the urine drug and alcohol screen Any regular use of prescription or nonprescription drugs or vitamins and herbal/nutritional supplements that cannot be stopped at screening Any strenuous exercise (as judged by the investigator) from 4 days prior to randomisation and during the entire trial period Blood donation, trauma or surgery with blood loss exceeding 500 ml within the last 2 months prior to dosing Subject is a smoker, occasional smoker or has a history of smoking (or use of any tobacco) within the last 3 months Excessive use of methylxanthine-containing beverages (more than 8 cups/day of coffee, tea, soda or chocolate) Females who are pregnant, breastfeeding, intend to become pregnant within the next 3 months, or who are judged to be using inadequate contraceptive measures A history (within the last 2 years) of drug or alcohol abuse

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Double-blind / liraglutide<br> | Drug: liraglutide<br>* 0.6 mg daily for 7 days followed by 1.2 mg daily for 7 days followed by 1.8 mg daily for 7 days. Injected subcutaneously. Subjects are randomly allocated to two treatment sequences<br>Drug: placebo<br>* Injected subcutaneously. Subjects are randomly allocated to two treatment sequences<br>Procedure: electrocardiogram (ECG)<br>* 24 hours serial ECG is collected before initial dose of 0.6 mg liraglutide, on the last dosing day of 1.2 mg liraglutide and on the last dosing day of 1.8 mg liraglutide<br>|
| Placebo Comparator: Double-blind / placebo<br> | Drug: liraglutide<br>* 0.6 mg daily for 7 days followed by 1.2 mg daily for 7 days followed by 1.8 mg daily for 7 days. Injected subcutaneously. Subjects are randomly allocated to two treatment sequences<br>Drug: placebo<br>* Injected subcutaneously. Subjects are randomly allocated to two treatment sequences<br>Procedure: electrocardiogram (ECG)<br>* 24 hours serial ECG is collected before initial dose of 0.6 mg liraglutide, on the last dosing day of 1.2 mg liraglutide and on the last dosing day of 1.8 mg liraglutide<br>|
| Active Comparator: Open-label / moxifloxacin<br> | Drug: moxifloxacin<br>* Following the double-blinded period and a wash-out period of 7 days, subjects are re-randomised to an open-label, parallel period where a single dose of 400 mg moxifloxacin (tablets) is administered as positive control<br>Procedure: electrocardiogram (ECG)<br>* Six hours after moxifloxacin or placebo single dose, 1 hour serial ECG is collected<br>|
| Placebo Comparator: Open-label / placebo<br> | Drug: placebo<br>* Following the double-blinded period and a wash-out period of 7 days, subjects are re-randomised to an open-label, parallel period where single dose of oral placebo is administered<br>Procedure: electrocardiogram (ECG)<br>* Six hours after moxifloxacin or placebo single dose, 1 hour serial ECG is collected<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum time-matched mean difference between the baseline subtracted QTci intervals |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| QTc at liraglutide tmax (time to reach maximum concentration) |  |  | 
| Percentage subjects with QTc at least 450, 480 and 500 milliseconds |  |  | 
| Moxifloxacin maximum time-matched mean change QTc and QTci |  |  | 
| Cmax, maximum concentration of liraglutide |  |  | 
| tmax, time to reach Cmax of liraglutide |  |  | 
| Vitals signs: Blood pressure |  |  | 
| Vital signs: Pulse |  |  | 
| Serial electrocardiography |  |  |