Clinical trial NCT01297062: A Safety Study to Assess the Effects of Therapeutic and Supratherapeutic Exenatide Concentrations on QT Interval in Healthy Subjects
Official title: A Randomized, Phase 1, Three-Period, Placebo- and Positive-Controlled, Double-Blind, Crossover Study to Assess the Electrophysiological Effects of Exenatide at Therapeutic and Supratherapeutic Concentrations on the 12-Lead Electrocardiogram QT Interval in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Keywords: Diabetes
exenatide
Amylin
Lilly
QT interval
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2011-02-16
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

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


Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: Baseline, Day 1
measure: 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)
timeFrame: Baseline, Day 2
measure: 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)
timeFrame: Baseline, Day 3
Secondary outcomes:
measure: Assay Sensitivity of Moxifloxacin at 1000h (1 Hour Post-administration of Moxifloxacin) on Day 2
timeFrame: Baseline, Day 2
measure: Assay Sensitivity of Moxifloxacin at 1100h (2 Hour Post-administration of Moxifloxacin) on Day 2
timeFrame: Baseline, Day 2
measure: Assay Sensitivity of Moxifloxacin at 1200h (3 Hour Post-administration of Moxifloxacin) on Day 2
timeFrame: Baseline, Day 2
measure: Number of Subjects With QTcP Interval >450msec at Any Timepoint on Any Day in Exenatide and Placebo
timeFrame: Day 1, 2, or 3
measure: Number of Subjects With Increase of QTcP Interval From Baseline >30msec at Any Timepoint on Any Day in Exenatide and Placebo
timeFrame: Baseline, Day 1, 2, or 3
measure: Plasma Exenatide Concentrations at Steady State on Day 1, 2 and 3
timeFrame: Baseline, Day 1, 2, and 3
Other outcomes:
Locations:
city: Daytona Beach
country: United States
facility: Research Site
state: Florida
city: Evansville
country: United States
facility: Research Site
state: Indiana
Study officials:
affiliation: Amylin Pharmaceuticals, LLC.
name: Vice President Research and Development, MD
role: STUDY_DIRECTOR
References: