Effect of Liraglutide on Heart Frequency in Healthy Volunteers

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Diabetes
• Intervention / Treatment: Drug: liraglutide; Drug: placebo; Drug: placebo; Procedure: electrocardiogram (ECG); Procedure: electrocardiogram (ECG); Drug: moxifloxacin

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Double-blind / liraglutide	Drug: liraglutide; 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; Drug: placebo; Injected subcutaneously. Subjects are randomly allocated to two treatment sequences; Drug: placebo; 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; Procedure: electrocardiogram (ECG); 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; Procedure: electrocardiogram (ECG); Six hours after moxifloxacin or placebo single dose, 1 hour serial ECG is collected
PLACEBO_COMPARATOR: Double-blind / placebo	Drug: liraglutide; 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; Drug: placebo; Injected subcutaneously. Subjects are randomly allocated to two treatment sequences; Drug: placebo; 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; Procedure: electrocardiogram (ECG); 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; Procedure: electrocardiogram (ECG); Six hours after moxifloxacin or placebo single dose, 1 hour serial ECG is collected
ACTIVE_COMPARATOR: Open-label / moxifloxacin	Procedure: electrocardiogram (ECG); 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; Procedure: electrocardiogram (ECG); Six hours after moxifloxacin or placebo single dose, 1 hour serial ECG is collected; Drug: moxifloxacin; 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
PLACEBO_COMPARATOR: Open-label / placebo	Drug: placebo; Injected subcutaneously. Subjects are randomly allocated to two treatment sequences; Drug: placebo; 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; Procedure: electrocardiogram (ECG); 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; Procedure: electrocardiogram (ECG); Six hours after moxifloxacin or placebo single dose, 1 hour serial ECG is collected

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Maximum time-matched mean difference between the baseline subtracted QTci intervals

Secondary Outcome Measures

Outcome Measure
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

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Chatterjee DJ, Khutoryansky N, Zdravkovic M, Sprenger CR, Litwin JS. Absence of QTc prolongation in a thorough QT study with subcutaneous liraglutide, a once-daily human GLP-1 analog for treatment of type 2 diabetes. J Clin Pharmacol. 2009 Nov;49(11):1353-62. doi: 10.1177/0091270009339189. Epub 2009 Sep 8.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (ACTUAL): November 1, 2006
• Study Completion (ACTUAL): November 1, 2006

Study Registration Dates

• First Submitted: January 19, 2012
• First Submitted That Met QC Criteria: January 19, 2012
• First Posted (ESTIMATE): January 24, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): January 25, 2017
• Last Update Submitted That Met QC Criteria: January 24, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Incretins; Moxifloxacin; Liraglutide
• Other Study ID Numbers: NN2211-1644