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

Condition(s) targeted: Healthy Subjects

Intervention: exenatide (Drug); moxifloxacin (Drug); placebo (Drug)

Phase: Phase 1

Status: Recruiting

Sponsored by: Amylin Pharmaceuticals, Inc.

Official(s) and/or principal investigator(s):
James Malone, MD, Study Director, Affiliation: Eli Lilly and Company

Overall contact:
Lilly Clinical Trials Support Center, Phone: 1-877-CTLILLY (1-877-285-4559)

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.

Official title: A Placebo- and Positive-Controlled Study of the Electrophysiological Effects of a Single 10 μg Dose of Exenatide on the 12-Lead Electrocardiogram QT Interval in Healthy Subjects

Study design: Basic Science, Randomized, Double Blind (Subject, Investigator), Crossover Assignment, Safety Study

Primary outcome: 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

Secondary outcome:

To evaluate the relationship between plasma exenatide concentrations and QTc interval in healthy subjects.

To explore the influence of potential physiological covariates such as plasma insulin, plasma glucose, and potassium on QTc interval in healthy subjects

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

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.

Lilly Clinical Trials Support Center, Phone: 1-877-CTLILLY (1-877-285-4559)

Reseach Site, Derriford, Plymouth, United Kingdom; Recruiting

Research Site, Leeds, West Yorkshire, United Kingdom; Recruiting

Starting date: April 2008
Ending date: August 2008
Last updated: July 14, 2008