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NCT Number: NCT01297062

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

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

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Key information

Conditions

Healthy Subjects Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Research Site, Daytona Beach, Florida, United States

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Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

exenatide

Drug

IV Exenatide (therapeutic and supratherapeutic concentrations)

moxifloxacin

Drug

Oral Moxifloxacin (400 mg)

placebo comparator

Drug

IV Placebo (matching volume of placebo)

Primary outcomes

  1. 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)

    Time frame: Baseline, Day 1

    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.

  2. 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)

    Time frame: Baseline, Day 2

    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.

  3. 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)

    Time frame: Baseline, Day 3

    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.

Secondary outcomes

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

    Time frame: Baseline, Day 2

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

  2. Assay Sensitivity of Moxifloxacin at 1100h (2 Hour Post-administration of Moxifloxacin) on Day 2

    Time frame: Baseline, Day 2

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

  3. Assay Sensitivity of Moxifloxacin at 1200h (3 Hour Post-administration of Moxifloxacin) on Day 2

    Time frame: Baseline, Day 2

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

  4. Number of Subjects With QTcP Interval >450msec at Any Timepoint on Any Day in Exenatide and Placebo

    Time frame: Day 1, 2, or 3

    Number of subjects with QTcP > 450 msec at any timepoint on any day was summarized by frequency for exenatide and placebo.

  5. Number of Subjects With Increase of QTcP Interval From Baseline >30msec at Any Timepoint on Any Day in Exenatide and Placebo

    Time frame: Baseline, Day 1, 2, or 3

    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.

  6. Plasma Exenatide Concentrations at Steady State on Day 1, 2 and 3

    Time frame: Baseline, 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.

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Collaborators

  • Eli Lilly and Company

Registry information

Official study 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

Important dates

Study start
2011
Primary completion
2011
Study completion
2011
First posted
Feb 16, 2011
Registry last updated
Apr 14, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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