NCT01297062 - A Safety Study to Assess the Effects of Therapeutic and Supratherapeutic Exenatide Concentrations on QT Interval in Healthy Subjects | Crick

Overview

Compare the effect of exenatide (therapeutic and supratherapeutic concentrations), moxifloxacin and placebo on the QT interval.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Masking

TRIPLE

Enrollment

94

Conditions

Healthy Subjects

Interventions

ExenatideDRUG

IV Exenatide (therapeutic and supratherapeutic concentrations)

MoxifloxacinDRUG

Oral Moxifloxacin (400 mg)

Placebo comparatorDRUG

IV Placebo (matching volume of placebo)

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Is overtly healthy, as determined by medical history and physical examination * Has body mass index (BMI) between 25 and 35 kg/m2 * Has fasting serum glucose \<110 mg/dL * Has no clinically significant blood pressure or heart rate readings as judged by the investigator at study start * Has electrocardiogram (ECG) results judged as not clinically significant by the investigator at study start Exclusion Criteria: * Has a clinically significant medical condition that could potentially affect study participation and/or personal well-being * Has an abnormality in the 12-lead ECG that, in the opinion of the investigator, increases the risk of participating in the study, such as a Bazett's corrected QT (QTcB) interval \>450 ms. * Family history of sudden death * Personal history of unexplained syncope within last year, or family history of Long QT Syndrome, or significant active cardiac disease, or symptoms of angina pectoris or transient ischemic attacks within the previous 6 months

Locations (2)

Research Site

Daytona Beach, Florida, United States

Research Site

Evansville, Indiana, United States

Outcomes

Primary Outcomes

Comparison of Least Squares (LS) Mean Changes From Baseline in Population-based Corrected QT Intervals (QTcP) Between Exenatide and Placebo on Day 1 Averaged Over 1300h, 1400h, 1500h (Target Steady State Exenatide Concentration of 200 pg/mL)

Factors in QT correction formulas were first estimated using pre-therapy data. The most appropriate correction method (QTcP) minimized the mean squared individual QTc/RR regression slope with on-exenatide data. Adequacy of correction was validated with on-placebo data. Change from baseline in QTcP was analyzed by a mixed-effects model for repeated measures (MMRM) between exenatide and placebo.

Time frame: Baseline, Day 1

Comparison of LS Mean Changes From Baseline in QTcP Intervals Between Exenatide and Placebo on Day 2 Averaged Over 1300h, 1400h, 1500h (Target Steady State Exenatide Concentration of 300 pg/mL)

Factors in QT correction formulas were first estimated using pre-therapy data. The most appropriate correction method (QTcP) minimized the mean squared individual QTc/RR regression slope with on-exenatide data. Adequacy of correction was validated with on-placebo data. Change from baseline in QTcP was analyzed by a MMRM between exenatide and placebo.

Time frame: Baseline, Day 2

Comparison of LS Mean Changes From Baseline in QTcP Intervals Between Exenatide and Placebo on Day 3 Averaged Over 1300h, 1400h, 1500h (Target Steady State Exenatide Concentration of 500 pg/mL)

Factors in QT correction formulas were first estimated using pre-therapy data. The most appropriate correction method (QTcP) minimized the mean squared individual QTc/RR regression slope with on-exenatide data. Adequacy of correction was validated with on-placebo data. Change from baseline in QTcP was analyzed by a MMRM between exenatide and placebo.

Time frame: Baseline, Day 3

Secondary Outcomes

Assay Sensitivity of Moxifloxacin at 1000h (1 Hour Post-administration of Moxifloxacin) on Day 2

Change from baseline in QTcP was analyzed by a MMRM between moxifloxacin and placebo.