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

NCT00672399 | Completed Phase 1

• 1 other identifier: H8O-EW-GWCI
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Healthy Subjects

Keywords

Amylin; Eli Lilly; exenatide; moxifloxacin

Outcome Measures

Primary Outcomes (1)

• Comparison of exenatide's effect on QT interval when compared to placebo

  To determine, in healthy subjects, that a single 10 μg dose of exenatide does not differ from placebo in the mean change from predose in 12-lead ECG correct QT (QTc) interval measurements

  single doses - measurements at 1, 2, 3, 4, 5.5 and 10 hours after dosing

Secondary Outcomes (2)

• Measurement of any QTcF changes following exenatide versus glucose, potassium, and insulin

  single doses - samples drawn at and EKGs at -15 min, hours 1, 2, 3, 4, 5.5, 10

• Assessment of plasma exenatide concentrations and QTc interval

  During Periods I, II, and III, ECGs should be recorded at the following

Study Arms (6)

Sequence 1

EXPERIMENTAL

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

Drug: exenatide; Drug: Moxifloxacin; Drug: Placebo

Sequence 2

EXPERIMENTAL

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

Drug: exenatide; Drug: Moxifloxacin; Drug: Placebo

Sequence 3

EXPERIMENTAL

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

Drug: exenatide; Drug: Moxifloxacin; Drug: Placebo

Sequence 4

EXPERIMENTAL

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

Drug: exenatide; Drug: Moxifloxacin; Drug: Placebo

Sequence 5

EXPERIMENTAL

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

Drug: exenatide; Drug: Moxifloxacin; Drug: Placebo

Sequence 6

EXPERIMENTAL

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

Drug: exenatide; Drug: Moxifloxacin; Drug: Placebo

Interventions

exenatide DRUG

Subcutaneously injected, 10 mcg, single doses

Also known as: Byetta

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6

Moxifloxacin DRUG

oral, 400 mg tablet, single doses

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6

Placebo DRUG

Subcutaneously injucted in an amount equivalent to exenatide; or orally as a tablet identical in appearance to Moxifloxacin. Both are single doses

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead
• Eli Lilly and Company: collaborator

Study Sites (2)

Reseach Site

Derriford, Plymouth, United Kingdom

Location

Research Site

Leeds, West Yorkshire, United Kingdom

Location

MeSH Terms

Interventions

Exenatide; Moxifloxacin

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• James Malone, MD

  Eli Lilly and Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2008
• First Posted: May 6, 2008
• Study Start: April 1, 2008
• Primary Completion: July 1, 2008
• Study Completion: July 1, 2008
• Last Updated: February 24, 2015

Record last verified: 2015-01

Locations

GB (2)