Effect of Liraglutide on Heart Frequency in Healthy Volunteers

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01516255
• Other study ID #: NN2211-1644
• Status: Completed
• Phase: Phase 1
• First received: January 19, 2012
• Last updated: January 24, 2017
• Start date: July 2006
• Est. completion date: November 2006

Study information

• Verified date: January 2017
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: November 2006
• Est. primary completion date: November 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

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
• placebo
Injected subcutaneously. Subjects are randomly allocated to two treatment sequences
• 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
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
• electrocardiogram (ECG)
Six hours after moxifloxacin or placebo single dose, 1 hour serial ECG is collected

Locations

Country	Name	City	State
United States	Novo Nordisk Investigational Site	Fargo	North Dakota

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum time-matched mean difference between the baseline subtracted QTci intervals
Secondary	QTc at liraglutide tmax (time to reach maximum concentration)
Secondary	Percentage subjects with QTc at least 450, 480 and 500 milliseconds
Secondary	Moxifloxacin maximum time-matched mean change QTc and QTci
Secondary	Cmax, maximum concentration of liraglutide
Secondary	tmax, time to reach Cmax of liraglutide
Secondary	Vitals signs: Blood pressure
Secondary	Vital signs: Pulse
Secondary	Serial electrocardiography

External Links

•   Clinical Trials at Novo Nordisk