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A Safety Study to Assess the Effects of Therapeutic and Supratherapeutic Exenatide Concentrations on 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:
NCT01297062
First received: February 9, 2011
Last updated: June 4, 2014
Last verified: June 2014

February 9, 2011
June 4, 2014
February 2011
April 2011   (final data collection date for primary outcome 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) [ Time Frame: Baseline, Day 1 ] [ Designated as safety issue: No ]
    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.
  • 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 ] [ Designated as safety issue: No ]
    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.
  • 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 ] [ Designated as safety issue: No ]
    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.
The mean change from predose in 12-lead electrocardiogram corrected QT interval. [ Time Frame: From baseline up to and including 3 days post initial dose during each crossover treatment period. ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01297062 on ClinicalTrials.gov Archive Site
  • Assay Sensitivity of Moxifloxacin at 1000h (1 Hour Post-administration of Moxifloxacin) on Day 2 [ Time Frame: Baseline, Day 2 ] [ Designated as safety issue: No ]
    Change from baseline in QTcP was analyzed by a MMRM between moxifloxacin and placebo.
  • Assay Sensitivity of Moxifloxacin at 1100h (2 Hour Post-administration of Moxifloxacin) on Day 2 [ Time Frame: Baseline, Day 2 ] [ Designated as safety issue: No ]
    Change from baseline in QTcP was analyzed by a MMRM between moxifloxacin and placebo.
  • Assay Sensitivity of Moxifloxacin at 1200h (3 Hour Post-administration of Moxifloxacin) on Day 2 [ Time Frame: Baseline, Day 2 ] [ Designated as safety issue: No ]
    Change from baseline in QTcP was analyzed by a MMRM between moxifloxacin and placebo.
  • Number of Subjects With QTcP Interval >450msec at Any Timepoint on Any Day in Exenatide and Placebo [ Time Frame: Day 1, 2, or 3 ] [ Designated as safety issue: No ]
    Number of subjects with QTcP > 450 msec at any timepoint on any day was summarized by frequency for exenatide and placebo.
  • 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 ] [ Designated as safety issue: No ]
    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.
  • Plasma Exenatide Concentrations at Steady State on Day 1, 2 and 3 [ Time Frame: Baseline, Day 1, 2, and 3 ] [ Designated as safety issue: No ]
    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.
  • To assess the pharmacokinetic-pharmacodynamic relationship between plasma concentration of exenatide at steady state and its effects, if any, on the QTc interval. [ Time Frame: From baseline up to and including 3 days post initial dose during each crossover treatment period. ] [ Designated as safety issue: Yes ]
  • The safety and tolerability of exenatide as assessed by the incidence, nature and severity of adverse events. [ Time Frame: From baseline up to and including 3 days post initial dose during each crossover treatment period. ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
A Safety Study to Assess the Effects of Therapeutic and Supratherapeutic Exenatide Concentrations on QT Interval in Healthy Subjects
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

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

Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Healthy Subjects
  • Drug: Exenatide
    IV Exenatide (therapeutic and supratherapeutic concentrations)
  • Drug: Moxifloxacin
    Oral Moxifloxacin (400 mg)
  • Drug: Placebo comparator
    IV Placebo (matching volume of placebo)
  • Experimental: Exenatide
    Intervention: Drug: Exenatide
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo comparator
  • Active Comparator: Moxifloxacin
    Intervention: Drug: Moxifloxacin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
94
May 2011
April 2011   (final data collection date for primary outcome measure)

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
Both
18 Years to 65 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01297062
BCB112
No
AstraZeneca
AstraZeneca
Eli Lilly and Company
Study Director: Vice President Research and Development, MD Amylin Pharmaceuticals, LLC.
AstraZeneca
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP