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

Purpose

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.

Condition	Intervention	Phase
Healthy Subjects	Drug: exenatide Drug: Moxifloxacin Drug: Placebo	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Basic Science
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

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Medicines

Drug Information available for: Exenatide Moxifloxacin Moxifloxacin hydrochloride

U.S. FDA Resources

Further study details as provided by Amylin Pharmaceuticals, LLC.:

Primary Outcome Measures:

Comparison of exenatide's effect on QT interval when compared to placebo [ Time Frame: single doses - measurements at 1, 2, 3, 4, 5.5 and 10 hours after dosing ] [ Designated as safety issue: No ]
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 Measures:

Measurement of any QTcF changes following exenatide versus glucose, potassium, and insulin [ Time Frame: single doses - samples drawn at and EKGs at -15 min, hours 1, 2, 3, 4, 5.5, 10 ] [ Designated as safety issue: No ]
To explore the influence of potential physiological covariates such as plasma insulin, plasma glucose, and potassium on QTc interval in healthy subjects
Assessment of plasma exenatide concentrations and QTc interval [ Time Frame: During Periods I, II, and III, ECGs should be recorded at the following ] [ Designated as safety issue: No ]
Evaluation of the relationship between plasma exenatide concentrations and QTc interval in healthy subjects

Enrollment:	70
Study Start Date:	April 2008
Study Completion Date:	July 2008
Primary Completion Date:	July 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Sequence 1 Period 1 = placebo exenatide/placebo moxifloxacin; Period II = exenatide/placebo moxifloxacin; Period III = placebo exenatide/moxifloxacin	Drug: exenatide Subcutaneously injected, 10 mcg, single doses Other Name: Byetta Drug: Moxifloxacin oral, 400 mg tablet, single doses Drug: Placebo Subcutaneously injucted in an amount equivalent to exenatide; or orally as a tablet identical in appearance to Moxifloxacin. Both are single doses
Experimental: Sequence 2 Period I = exenatide/placebo moxifloxacin; Period II = placebo exenatide/moxifloxacin; Period III = placebo exenatide/placebo moxifloxacin	Drug: exenatide Subcutaneously injected, 10 mcg, single doses Other Name: Byetta Drug: Moxifloxacin oral, 400 mg tablet, single doses Drug: Placebo Subcutaneously injucted in an amount equivalent to exenatide; or orally as a tablet identical in appearance to Moxifloxacin. Both are single doses
Experimental: Sequence 3 Period 1 = placebo exenatide/moxifloxacin; Period II = placebo exenatide/moxifloxacin; Period III = exenatide/placebo moxifloxacin	Drug: exenatide Subcutaneously injected, 10 mcg, single doses Other Name: Byetta Drug: Moxifloxacin oral, 400 mg tablet, single doses Drug: Placebo Subcutaneously injucted in an amount equivalent to exenatide; or orally as a tablet identical in appearance to Moxifloxacin. Both are single doses
Experimental: Sequence 4 Period I = placebo exenatide/moxifloxacin; Period II = exenatide/placebo moxifloxacin; Period III = placebo exenatide/placebo moxifloxacin	Drug: exenatide Subcutaneously injected, 10 mcg, single doses Other Name: Byetta Drug: Moxifloxacin oral, 400 mg tablet, single doses Drug: Placebo Subcutaneously injucted in an amount equivalent to exenatide; or orally as a tablet identical in appearance to Moxifloxacin. Both are single doses
Experimental: Sequence 5 Period I = placebo exenatide/placebo moxifloxacin; Period II = placebo exenatide/moxifloxacin; Period III = exenatide/moxifloxacin	Drug: exenatide Subcutaneously injected, 10 mcg, single doses Other Name: Byetta Drug: Moxifloxacin oral, 400 mg tablet, single doses Drug: Placebo Subcutaneously injucted in an amount equivalent to exenatide; or orally as a tablet identical in appearance to Moxifloxacin. Both are single doses
Experimental: Sequence 6 Period I = exenatide/placebo moxifloxacin; Period II = placebo exenatide/placebo moxifloxacin; Period III = placebo exenatide/moxifloxacin	Drug: exenatide Subcutaneously injected, 10 mcg, single doses Other Name: Byetta Drug: Moxifloxacin oral, 400 mg tablet, single doses Drug: Placebo Subcutaneously injucted in an amount equivalent to exenatide; or orally as a tablet identical in appearance to Moxifloxacin. Both are single doses

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00672399

Locations

United Kingdom
Reseach Site
Derriford, Plymouth, United Kingdom
Research Site
Leeds, West Yorkshire, United Kingdom

Sponsors and Collaborators

Amylin Pharmaceuticals, LLC.

Eli Lilly and Company

Investigators

Study Director:

James Malone, MD

Eli Lilly and Company

More Information

No publications provided

Responsible Party:	Amylin Pharmaceuticals, LLC.
ClinicalTrials.gov Identifier:	NCT00672399 History of Changes
Other Study ID Numbers:	H8O-EW-GWCI
Study First Received:	May 1, 2008
Last Updated:	February 6, 2013
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Amylin Pharmaceuticals, LLC.:

Amylin
Eli Lilly
exenatide
moxifloxacin

Additional relevant MeSH terms:

Exenatide
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Infective Agents

Therapeutic Uses
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents

ClinicalTrials.gov processed this record on May 23, 2013