Clinical Trial: Study of the Effect of GS-6615 in Subjects With LQT-3

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: An Open-label Study to Evaluate the Effect of Single Dose GS-6615 on QT, Safety and Tolerability in Subjects With Long QT-3 Syndrome

Brief Summary:

This mechanism of action study is to evaluate the effect of oral GS-6615 on the QTc interval in participants with Long QT-3 syndrome. This study will be performed in six cohorts of participants in a sequential manner, four single-dose cohorts followed by two multiple-dose cohorts. Duration of treatment for the single-dose cohorts and multiple-dose cohorts will be 1 day and 7 days, respectively. Participants will be confined at the study center from check-in until completion of assessments at discharge.

Participants will be continuously monitored using real-time telemetry throughout the in-clinic confinement. Physical examinations including vital signs, laboratory analysis, electrocardiograms (ECGs), Holter recordings and echocardiography (ECHO) will be performed at defined time points throughout the study period. Assessment of adverse events and concomitant medications will continue throughout the duration of the study.


Detailed Summary:
Sponsor: Gilead Sciences

Current Primary Outcome: Changes in QTc intervals (Fridericia formula) [ Time Frame: Baseline through Day 7 ]

Changes in QTc intervals (Fridericia formula; QTcF) from the time-matched ECG in the primary lead V5. In case QT cannot be measured in lead V5, lead II will be designated as the primary lead

  • Change from the time-matched ECG on Day -1 to Day 1 for Cohorts 1-4
  • Change from the time-matched ECG average of Day -1 and Day -2 to Days 1-7 for Cohort 5 and 6


Original Primary Outcome:

  • Changes in QTc intervals [ Time Frame: From baseline through Day 4 ]
    QT interval corrected for heart rate using the Bazett (QTcB) or Fridericia (QTcF) formula
  • Percent changes in QTc intervals [ Time Frame: From baseline through Day 4 ]
    QT interval corrected for heart rate using the Bazett (QTcB) or Fridericia (QTcF) formula


Current Secondary Outcome:

  • Incidence of Adverse Events (AEs) [ Time Frame: Baseline through Day 22 ]
  • Changes in ECHO parameters [ Time Frame: Baseline through Day 7 ]
    ECHO parameters relevant for measurement of diastolic function will be assessed.
  • Area under the plasma concentration-time curve (AUC) from time 0 to the last quantifiable concentration of GS-6615 [ Time Frame: Baseline through Day 12 ]
  • Maximum observed plasma concentration (Cmax) of GS-6615 [ Time Frame: Baseline through Day 12 ]
  • Time to maximum observed concentration (Tmax) of GS-6615 [ Time Frame: Baseline through Day 12 ]
  • Changes in ECG parameters [ Time Frame: Baseline through Day 12 ]

    ECG parameters assessed will include PR, RR, QRS, and QT.

    • PR: electrocardiographic interval occurring between the onset of the P wave and the QRS complex representing time for atrial and ventricular depolarization, respectively
    • RR: electrocardiographic interval representing the time measurement between the R wave of one heartbeat and the R wave of the preceding heartbeat
    • QRS: electrocardiographic deflection between the beginning of the Q wave and termination of the S wave representing time for ventricular depolarization
    • QT: electrocardiographic interval between the beginning of the Q wave and termination of the T wave representing the time for both ventricular depolarization and repolarization to occur
  • Changes in QTc interval (Bazett [QTcB]) [ Time Frame: Baseline through Day 7 ]

    Changes in QTcB from the time-matched ECG in the primary lead V5. In case QT cannot be measured in lead V5, lead II will be designated as the primary lead

    • Change from the time-matched ECG on Day -1 to Day 1 for Cohorts 1-4
    • Change from the time-matched ECG average of Day -1 and Day -2 to Days 1-7 for Cohort 5 and 6


Original Secondary Outcome:

  • Incidence of Adverse Events (AEs) [ Time Frame: Through Day 14 ]
  • Changes in ECHO parameters [ Time Frame: From baseline through Day 1 ]
    ECHO parameters relevant for measurement of diastolic function will be assessed.
  • Area under the plasma concentration-time curve (AUC) from time 0 to the last quantifiable concentration of GS-6615 [ Time Frame: Through Day 4 ]
  • Maximum observed plasma concentration (Cmax) of GS-6615 [ Time Frame: Through Day 4 ]
  • Time to maximum observed concentration (Tmax) of GS-6615 [ Time Frame: Through Day 4 ]
  • Changes in ECG parameters [ Time Frame: From baseline through Day 4 ]
    ECG parameters assessed will include PR, RR, QRS, QT and QTc interval (Bazett and Fridericia).
  • Percent changes in ECHO parameters [ Time Frame: From baseline through Day 1 ]
    ECHO parameters relevant for measurement of diastolic function will be assessed.
  • Percent changes in ECG parameters [ Time Frame: From baseline through Day 4 ]
    ECG parameters assessed will include PR, RR, QRS, QT and QTc interval (Bazett and Fridericia).
  • Relationship between plasma concentrations of GS-6615 and the changes in QTc interval [ Time Frame: From baseline through Day 4 ]


Information By: Gilead Sciences

Dates:
Date Received: May 6, 2013
Date Started: May 2013
Date Completion:
Last Updated: November 13, 2014
Last Verified: November 2014