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

Healthy Subjects Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01297062
• Other study ID #: BCB112
• Status: Completed
• Phase: Phase 1
• First received: February 9, 2011
• Last updated: March 24, 2015
• Start date: February 2011
• Est. completion date: May 2011

Study information

• Verified date: March 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 94
• Est. completion date: May 2011
• Est. primary completion date: April 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

Drug:
• Exenatide
IV Exenatide (therapeutic and supratherapeutic concentrations)
• Moxifloxacin
Oral Moxifloxacin (400 mg)
• Placebo comparator
IV Placebo (matching volume of placebo)

Locations

Country	Name	City	State
United States	Research Site	Daytona Beach	Florida
United States	Research Site	Evansville	Indiana

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Eli Lilly and Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline, Day 1	No
Primary	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.	Baseline, Day 2	No
Primary	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.	Baseline, Day 3	No
Secondary	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.	Baseline, Day 2	No
Secondary	Assay Sensitivity of Moxifloxacin at 1100h (2 Hour Post-administration of Moxifloxacin) on Day 2	Change from baseline in QTcP was analyzed by a MMRM between moxifloxacin and placebo.	Baseline, Day 2	No
Secondary	Assay Sensitivity of Moxifloxacin at 1200h (3 Hour Post-administration of Moxifloxacin) on Day 2	Change from baseline in QTcP was analyzed by a MMRM between moxifloxacin and placebo.	Baseline, Day 2	No
Secondary	Number of Subjects With QTcP Interval >450msec at Any Timepoint on Any Day in Exenatide and Placebo	Number of subjects with QTcP > 450 msec at any timepoint on any day was summarized by frequency for exenatide and placebo.	Day 1, 2, or 3	No
Secondary	Number of Subjects With Increase of QTcP Interval From Baseline >30msec at Any Timepoint on Any Day in Exenatide and Placebo	Number of subjects with increase of QTcP interval from baseline >30 msec at any timepoint on any day was summarized by frequency for exenatide and placebo.	Baseline, Day 1, 2, or 3	No
Secondary	Plasma Exenatide Concentrations at Steady State on Day 1, 2 and 3	The plasma exenatide concentration at steady state was descriptively summarized by geometric mean, standard error, and its effect on placebo-adjusted change from baseline in QTcP was assessed.	Baseline, Day 1, 2, and 3	No