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

Study Overview
=================
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.

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

Conditions
-----------------
Healthy Subjects

Intervention / Treatment
-----------------
* Drug: exenatide
* Drug: Moxifloxacin
* Drug: Placebo


Participation Criteria
=================
Eligibility 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1<br>Period 1 = placebo exenatide/placebo moxifloxacin; Period II = exenatide/placebo moxifloxacin; Period III = placebo exenatide/moxifloxacin | Drug: exenatide<br>* Subcutaneously injected, 10 mcg, single doses<br>* Other names: Byetta;Drug: Moxifloxacin<br>* oral, 400 mg tablet, single doses<br>Drug: Placebo<br>* Subcutaneously injucted in an amount equivalent to exenatide; or orally as a tablet identical in appearance to Moxifloxacin. Both are single doses<br>|
| Experimental: Sequence 2<br>Period I = exenatide/placebo moxifloxacin; Period II = placebo exenatide/moxifloxacin; Period III = placebo exenatide/placebo moxifloxacin | Drug: exenatide<br>* Subcutaneously injected, 10 mcg, single doses<br>* Other names: Byetta;Drug: Moxifloxacin<br>* oral, 400 mg tablet, single doses<br>Drug: Placebo<br>* Subcutaneously injucted in an amount equivalent to exenatide; or orally as a tablet identical in appearance to Moxifloxacin. Both are single doses<br>|
| Experimental: Sequence 3<br>Period 1 = placebo exenatide/moxifloxacin; Period II = placebo exenatide/moxifloxacin; Period III = exenatide/placebo moxifloxacin | Drug: exenatide<br>* Subcutaneously injected, 10 mcg, single doses<br>* Other names: Byetta;Drug: Moxifloxacin<br>* oral, 400 mg tablet, single doses<br>Drug: Placebo<br>* Subcutaneously injucted in an amount equivalent to exenatide; or orally as a tablet identical in appearance to Moxifloxacin. Both are single doses<br>|
| Experimental: Sequence 4<br>Period I = placebo exenatide/moxifloxacin; Period II = exenatide/placebo moxifloxacin; Period III = placebo exenatide/placebo moxifloxacin | Drug: exenatide<br>* Subcutaneously injected, 10 mcg, single doses<br>* Other names: Byetta;Drug: Moxifloxacin<br>* oral, 400 mg tablet, single doses<br>Drug: Placebo<br>* Subcutaneously injucted in an amount equivalent to exenatide; or orally as a tablet identical in appearance to Moxifloxacin. Both are single doses<br>|
| Experimental: Sequence 5<br>Period I = placebo exenatide/placebo moxifloxacin; Period II = placebo exenatide/moxifloxacin; Period III = exenatide/moxifloxacin | Drug: exenatide<br>* Subcutaneously injected, 10 mcg, single doses<br>* Other names: Byetta;Drug: Moxifloxacin<br>* oral, 400 mg tablet, single doses<br>Drug: Placebo<br>* Subcutaneously injucted in an amount equivalent to exenatide; or orally as a tablet identical in appearance to Moxifloxacin. Both are single doses<br>|
| Experimental: Sequence 6<br>Period I = exenatide/placebo moxifloxacin; Period II = placebo exenatide/placebo moxifloxacin; Period III = placebo exenatide/moxifloxacin | Drug: exenatide<br>* Subcutaneously injected, 10 mcg, single doses<br>* Other names: Byetta;Drug: Moxifloxacin<br>* oral, 400 mg tablet, single doses<br>Drug: Placebo<br>* Subcutaneously injucted in an amount equivalent to exenatide; or orally as a tablet identical in appearance to Moxifloxacin. Both are single doses<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of any QTcF changes following exenatide versus glucose, potassium, and insulin | To explore the influence of potential physiological covariates such as plasma insulin, plasma glucose, and potassium on QTc interval in healthy subjects | 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 | Evaluation of the relationship between plasma exenatide concentrations and QTc interval in healthy subjects | During Periods I, II, and III, ECGs should be recorded at the following | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Amylin, Eli Lilly, exenatide, moxifloxacin