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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):
Amylin Pharmaceuticals, LLC.
ClinicalTrials.gov Identifier:
NCT01297062
First received: February 9, 2011
Last updated: June 1, 2012
Last verified: June 2012
History of Changes
Results First Received: April 27, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Crossover Assignment;   Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Condition: Healthy Subjects
Interventions: Drug: Exenatide
Drug: Moxifloxacin
Drug: Placebo comparator

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
Placebo-Exenatide-Moxifloxacin Sequence

Placebo comparator in Period I; Exenatide in Period II; Moxifloxacin with placebo infusion in Period III;

Exenatide - stepped intravenous (IV) infusion to gradually deliver levels of exenatide at concentrations of approximately 200 pg/mL (Day 1), 300 pg/mL (Day 2), and 500 pg/mL (Day 3)

Moxifloxacin - Placebo intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) with single oral dose of Moxifloxacin (400 mg) on Day 2

Placebo - intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) on Day 1, Day 2, and Day 3
Exenatide-Moxifloxacin-Placebo Sequence

Exenatide in Period I; Moxifloxacin with placebo infusion in Period II; Placebo comparator in Period III

Exenatide - stepped intravenous (IV) infusion to gradually deliver levels of exenatide at concentrations of approximately 200 pg/mL (Day 1), 300 pg/mL (Day 2), and 500 pg/mL (Day 3)

Moxifloxacin - Placebo intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) with single oral dose of Moxifloxacin (400 mg) on Day 2

Placebo - intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) on Day 1, Day 2, and Day 3
Moxifloxacin-Placebo-Exenatide Sequence

Moxifloxacin with placebo infusion in Period I; Placebo comparator in Period II; Exenatide in Period III

Exenatide - stepped intravenous (IV) infusion to gradually deliver levels of exenatide at concentrations of approximately 200 pg/mL (Day 1), 300 pg/mL (Day 2), and 500 pg/mL (Day 3)

Moxifloxacin - Placebo intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) with single oral dose of Moxifloxacin (400 mg) on Day 2

Placebo - intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) on Day 1, Day 2, and Day 3
Moxifloxacin-Exenatide-Placebo Sequence

Moxifloxacin with placebo infusion in Period I; Exenatide in Period II; Placebo comparator in Period III

Exenatide - stepped intravenous (IV) infusion to gradually deliver levels of exenatide at concentrations of approximately 200 pg/mL (Day 1), 300 pg/mL (Day 2), and 500 pg/mL (Day 3)

Moxifloxacin - Placebo intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) with single oral dose of Moxifloxacin (400 mg) on Day 2

Placebo - intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) on Day 1, Day 2, and Day 3
Placebo-Moxifloxacin-Exenatiden Sequence

Placebo comparator in Period I; Moxifloxacin with placebo infusion in Period II; Exenatide in Period III

Exenatide - stepped intravenous (IV) infusion to gradually deliver levels of exenatide at concentrations of approximately 200 pg/mL (Day 1), 300 pg/mL (Day 2), and 500 pg/mL (Day 3)

Moxifloxacin - Placebo intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) with single oral dose of Moxifloxacin (400 mg) on Day 2

Placebo - intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) on Day 1, Day 2, and Day 3
Exenatide-Placebo-Moxifloxacin Sequence

Exenatide in Period I; Placebo comparator in Period II; Moxifloxacin with placebo infusion in Period III

Exenatide - stepped intravenous (IV) infusion to gradually deliver levels of exenatide at concentrations of approximately 200 pg/mL (Day 1), 300 pg/mL (Day 2), and 500 pg/mL (Day 3)

Moxifloxacin - Placebo intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) with single oral dose of Moxifloxacin (400 mg) on Day 2

Placebo - intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) on Day 1, Day 2, and Day 3
Non-Randomized Not Randomized

Participant Flow:   Overall Study
    Placebo-Exenatide-Moxifloxacin Sequence     Exenatide-Moxifloxacin-Placebo Sequence     Moxifloxacin-Placebo-Exenatide Sequence     Moxifloxacin-Exenatide-Placebo Sequence     Placebo-Moxifloxacin-Exenatiden Sequence     Exenatide-Placebo-Moxifloxacin Sequence     Non-Randomized  
STARTED     15     14     14     14     15     14     8  
Intent to Treat (ITT)     15     14     14     14     15     14     0  
Evaluable Population     11     12     12     13     13     13     0  
COMPLETED     11     13     12     13     13     13     0  
NOT COMPLETED     4     1     2     1     2     1     8  
Adverse Event                 2                 0                 1                 0                 0                 0                 0  
Physician Decision                 1                 0                 1                 0                 0                 0                 6  
Protocol Violation                 0                 0                 0                 0                 1                 0                 0  
Subject Decision                 1                 1                 0                 1                 1                 1                 2  



  Baseline Characteristics
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Reporting Groups
  Description
Placebo-Exenatide-Moxifloxacin Sequence Placebo comparator in Period I; Exenatide in Period II; Moxifloxacin with placebo infusion in Period III
Exenatide-Moxifloxacin-Placebo Sequence Exenatide in Period I; Moxifloxacin with placebo infusion in Period II; Placebo comparator in Period III
Moxifloxacin-Placebo-Exenatide Sequence Moxifloxacin with placebo infusion in Period I; Placebo comparator in Period II; Exenatide in Period III
Moxifloxacin-Exenatide-Placebo Sequence Moxifloxacin with placebo infusion in Period I; Exenatide in Period II; Placebo comparator in Period III
Placebo-Moxifloxacin-Exenatiden Sequence Placebo comparator in Period I; Moxifloxacin with placebo infusion in Period II; Exenatide in Period III
Exenatide-Placebo-Moxifloxacin Sequence Exenatide in Period I; Placebo comparator in Period II; Moxifloxacin with placebo infusion in Period III
Total Total of all reporting groups

Baseline Measures
    Placebo-Exenatide-Moxifloxacin Sequence     Exenatide-Moxifloxacin-Placebo Sequence     Moxifloxacin-Placebo-Exenatide Sequence     Moxifloxacin-Exenatide-Placebo Sequence     Placebo-Moxifloxacin-Exenatiden Sequence     Exenatide-Placebo-Moxifloxacin Sequence     Total  
Number of Participants  
[units: participants]
 		  15     14     14     14     15     14     86  
Age  
[units: years]
Mean ± Standard Deviation 		  41.5  ± 8.98     45.1  ± 11.43     43.7  ± 11.56     37.8  ± 10.66     43.3  ± 13.74     41.0  ± 10.50     42.1  ± 11.16  
Gender  
[units: participants]
 		             
Female     0     2     3     0     2     1     8  
Male     15     12     11     14     13     13     78  
Weight  
[units: kilogram]
Mean ± Standard Deviation 		  87.66  ± 8.107     81.16  ± 11.235     90.77  ± 12.375     93.66  ± 11.704     89.71  ± 7.726     90.71  ± 11.251     88.94  ± 10.899  



  Outcome Measures
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1.  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)   [ Time Frame: Baseline, Day 1 ]
  Show Outcome Measure 1

2.  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)   [ Time Frame: Baseline, Day 2 ]
  Show Outcome Measure 2

3.  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)   [ Time Frame: Baseline, Day 3 ]
  Show Outcome Measure 3

4.  Secondary:   Assay Sensitivity of Moxifloxacin at 1000h (1 Hour Post-administration of Moxifloxacin) on Day 2   [ Time Frame: Baseline, Day 2 ]
  Show Outcome Measure 4

5.  Secondary:   Assay Sensitivity of Moxifloxacin at 1100h (2 Hour Post-administration of Moxifloxacin) on Day 2   [ Time Frame: Baseline, Day 2 ]
  Show Outcome Measure 5

6.  Secondary:   Assay Sensitivity of Moxifloxacin at 1200h (3 Hour Post-administration of Moxifloxacin) on Day 2   [ Time Frame: Baseline, Day 2 ]
  Show Outcome Measure 6

7.  Secondary:   Number of Subjects With QTcP Interval >450msec at Any Timepoint on Any Day in Exenatide and Placebo   [ Time Frame: Day 1, 2, or 3 ]
  Show Outcome Measure 7

8.  Secondary:   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 ]
  Show Outcome Measure 8

9.  Secondary:   Plasma Exenatide Concentrations at Steady State on Day 1, 2 and 3   [ Time Frame: Baseline, Day 1, 2, and 3 ]
  Show Outcome Measure 9


  Serious Adverse Events
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  Other Adverse Events
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:  
Name/Title: Vice President, Research and Development
Organization: Amylin Pharmaceuticals
e-mail: clinicaltrials@amylin.com


No publications provided


Responsible Party: Amylin Pharmaceuticals, LLC.
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 1, 2012
Health Authority: United States: Food and Drug Administration