Electrophysiological Effects of a Single 10 μg Dose of Exenatide on the 12-Lead Electrocardiogram QT Interval in Healthy Subjects

AstraZeneca

Status and phase: Completed; Phase 1

Conditions: Healthy Subjects

Treatments: Drug: Moxifloxacin; Drug: exenatide; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00672399

H8O-EW-GWCI

Details and patient eligibility

About

This Phase 1, randomized, three period, placebo- and positive-controlled,double-blind, double-dummy, crossover study will be performed with approximately 80 healthy male and female subjects. The effects of single doses of exenatide (10 μg, subcutaneous), moxifloxacin (400 mg, oral) or placebo(subcutaneous or oral) on QT interval will be assessed.

Enrollment: 70 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Are between the ages of 18 and 65 years, inclusive.
• Have body mass index (BMI) between 19 and 35 kg/m2, inclusive.
• If females, are not of child-bearing potential due to surgical sterilisation (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause. Women with an intact uterus are deemed postmenopausal if they have had cessation of menses for at least 1 year or 6 to 12 months of spontaneous amenorrhea with follicle stimulating hormone >40 IU/mL; age ≥45 years; not taking oral contraceptives for at least 1 year; and otherwise healthy.
• Subjects receiving hormone replacement therapy (HRT) or thyroxine as replacement therapy may participate providing they have been on stable therapy for at least 3 months and have a normal thyroid stimulating hormone (TSH) value.

Exclusion criteria

• Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
• Known allergies to exenatide or excipients, moxifloxacin or related compounds, or a history of multiple adverse drug allergies of any origin.
• Family history of sudden death.
• Personal history of unexplained syncope within last year.
• History or presence of cardiovascular (myocardial infarction, cerebrovascular accident, venous thromboembolism), respiratory, hepatic, renal, GI, endocrine, haematological, or neurological disorders.
• Evidence or history of Long QT Syndrome or significant active cardiac disease (e.g., arrhythmia, hypertension, congestive heart failure, hypokalaemia, mitral valve regurgitation, endocarditis, coronary artery heart disease), or symptoms of angina pectoris or transient ischaemic attacks within the previous 6 months.
• Females who are lactating.
• Have previously completed or withdrawn from this study or any other study investigating exenatide.
• Evidence of human immunodeficiency virus (HIV) and/or positive human HIV antibodies.
• Evidence of hepatitis C and/or positive hepatitis C antibody.
• Evidence of hepatitis B and/or positive hepatitis B surface antigen.
• Use of over-the-counter or prescription medication (other than, for example, thyroid replacement, occasional intake of paracetamol, or vitamin or mineral supplements) 7 and 14 days, respectively, before dosing and throughout the study.
• Cumulative blood donation of more than 500 mL within the last 3 months.
• Subjects who have an average weekly alcohol intake that exceeds 28 units per week (males) and 21 units per week (females), or subjects unwilling to stop alcohol consumption for the duration of the study(1 unit = 12 oz or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits).
• Subjects who smoke or have smoked within 28 days of their screening visit and who are unable to abide by the study restrictions.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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70 participants in 6 patient groups

Sequence 1

Experimental group

Description:

Period 1 = placebo exenatide/placebo moxifloxacin; Period II = exenatide/placebo moxifloxacin; Period III = placebo exenatide/moxifloxacin

Treatment:

Drug: Moxifloxacin

Drug: exenatide

Drug: Placebo

Sequence 2

Experimental group

Description:

Period I = exenatide/placebo moxifloxacin; Period II = placebo exenatide/moxifloxacin; Period III = placebo exenatide/placebo moxifloxacin

Treatment:

Drug: Moxifloxacin

Drug: exenatide

Drug: Placebo

Sequence 3

Experimental group

Description:

Period 1 = placebo exenatide/moxifloxacin; Period II = placebo exenatide/moxifloxacin; Period III = exenatide/placebo moxifloxacin

Treatment:

Drug: Moxifloxacin

Drug: exenatide

Drug: Placebo

Sequence 4

Experimental group

Description:

Period I = placebo exenatide/moxifloxacin; Period II = exenatide/placebo moxifloxacin; Period III = placebo exenatide/placebo moxifloxacin

Treatment:

Drug: Moxifloxacin

Drug: exenatide

Drug: Placebo

Sequence 5

Experimental group

Description:

Period I = placebo exenatide/placebo moxifloxacin; Period II = placebo exenatide/moxifloxacin; Period III = exenatide/moxifloxacin

Treatment:

Drug: Moxifloxacin

Drug: exenatide

Drug: Placebo

Sequence 6

Experimental group

Description:

Period I = exenatide/placebo moxifloxacin; Period II = placebo exenatide/placebo moxifloxacin; Period III = placebo exenatide/moxifloxacin

Treatment:

Drug: Moxifloxacin

Drug: exenatide

Drug: Placebo