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
  Purpose

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


Condition Intervention Phase
Healthy Subjects
Drug: Exenatide
Drug: Moxifloxacin
Drug: Placebo comparator
Phase 1

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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 94
Study Start Date: February 2011
Study Completion Date: May 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Exenatide Drug: Exenatide
IV Exenatide (therapeutic and supratherapeutic concentrations)
Placebo Comparator: Placebo Drug: Placebo comparator
IV Placebo (matching volume of placebo)
Active Comparator: Moxifloxacin Drug: Moxifloxacin
Oral Moxifloxacin (400 mg)

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01297062

Locations
United States, Florida
Research Site
Daytona Beach, Florida, United States
United States, Indiana
Research Site
Evansville, Indiana, United States
Sponsors and Collaborators
AstraZeneca
Eli Lilly and Company
Investigators
Study Director: Vice President Research and Development, MD Amylin Pharmaceuticals, LLC.
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01297062     History of Changes
Other Study ID Numbers: BCB112
Study First Received: February 9, 2011
Results First Received: April 27, 2012
Last Updated: June 4, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by AstraZeneca:
Diabetes
exenatide
Amylin
Lilly
QT interval

Additional relevant MeSH terms:
Exenatide
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Infective Agents
Therapeutic Uses
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents

ClinicalTrials.gov processed this record on July 24, 2014