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

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00672399
First received: May 1, 2008
Last updated: June 6, 2014
Last verified: June 2014
  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:


Further study details as provided by AstraZeneca:

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
AstraZeneca
Eli Lilly and Company
Investigators
Study Director: James Malone, MD Eli Lilly and Company
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00672399     History of Changes
Other Study ID Numbers: H8O-EW-GWCI
Study First Received: May 1, 2008
Last Updated: June 6, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by AstraZeneca:
Amylin
Eli Lilly
exenatide
moxifloxacin

Additional relevant MeSH terms:
Exenatide
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Anti-Bacterial Agents
Anti-Infective Agents
Antineoplastic Agents
Contraceptive Agents
Contraceptive Agents, Female
Contraceptives, Oral
Contraceptives, Oral, Combined
Enzyme Inhibitors
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Hypoglycemic Agents
Incretins
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on November 25, 2014