GSK Investigational Site
Overland Park, Kansas, 66211, United States
NCT Number: NCT02027454
This study is being conducted to comply with the Food and Drug Administration (FDA) recommendation that all new non anti-arrhythmic drugs be assessed for cardiac repolarization effects through electrocardiographic evaluation. Therefore, this study will evaluate the effect of GSK1265744 on cardiac conduction as assessed by collection of twelve-lead continuous digital data in healthy adults. This study will evaluate the effect of three doses of GSK1265744 on the QT duration corrected for heart rate (QTc) interval as compared to placebo. Moxifloxacin will be used as a positive control in order to validate the sensitivity of the study in detecting QTc change. This study consists of three treatment periods (each separated by 21 day washout period) followed by follow-up visit 10 to 14 days post last dosing. The total duration of study including follow-up visit will be approximately 62 days. Approximately 42 subjects will be enrolled such that 34 subjects complete dosing and critical assessments.
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Notify Me18 year–55 year
All sexes
Interventional
Phase 1
Overland Park, Kansas, 66211, United States
Healthy volunteers accepted: Yes
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Exclusion criteria
Evidence of previous myocardial infarction (Does not include ST segment changes associated with repolarization).
Any conduction abnormality (including but not specific to left or right complete bundle branch block, atrioventricular block [2nd degree or higher], Wolf Parkinson White syndrome).
Sinus Pauses > 3 seconds. Any significant arrhythmia which, in the opinion of the principal investigator and GSK medical monitor, will interfere with the safety for the individual subject.
Non-sustained or sustained ventricular tachycardia (>=3 consecutive ventricular ectopic beats).
White to slightly colored film coated tablet with unit dose strength of 30 mg and dose level of 150mg (5 tablets of 3 mg) administered orally every 12hours for 3 doses.
GSK1265744 matching placebo tablets administered orally every 12hours for 3 doses (5 tablets per dose).
Dull red, oblong, convex film coated tablets with unit dose strength of 400 mg administered orally as a single dose.
Time frame: Baseline on Day -1 and Day 2 for Periods 1 - 3 (49 Days)
QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. QTcF interval will be obtained by digital electrocardiograms (ECG) obtained through 12 lead holter monitoring machine. Triplicate ECGs will be evaluated at each time point
Time frame: Baseline on Day -1 and Day 2 for Periods 1 - 3 (49 Days).
Single ECG will be obtained at all timepoints during the study using an ECG machine that automatically measures PR (beginning of P wave to the beginning of the next QRS), QRS (beginning of Q to the end of the S wave), QT, and QTc intervals.
Time frame: Baseline on Day -1 and Day 2 for Periods 1 - 3 (49 Days).
Single ECGs will be obtained at all timepoints during the study using an ECG machine that automatically calculates the heart rate. Heart rate is defined as the number of heartbeats per unit of time, usually per minute.
Time frame: Baseline on Day -1 and Day 2 for Periods 1 - 3 (49 Days).
Single ECGs will be obtained at all timepoints during the study using an ECG machine that automatically calculates the QTcF, QTcB, QTCi, QT, QRS, PR intervals
Time frame: Baseline on Day -1 and Day 2 for Periods 1 - 3 (49 Days).
Single ECGs will be obtained at all timepoints during the study using an ECG machine that automatically calculates the heart rate. Heart rate is defined as the number of heartbeats per unit of time, usually per minute.
Time frame: Baseline on Day -1 and Day 2 for Periods 1 - 3 (49 Days).
Single ECGs will be obtained at all timepoints during the study using an ECG machine that automatically calculates the QTcF, QTcB, QTCi, QT, QRS, PR intervals
Time frame: Baseline on Day -1 and Day 2 for Periods 1 - 3 (49 Days).
Single ECGs will be obtained at all timepoints during the study using an ECG machine that automatically calculates the heart rate. Heart rate is defined as the number of heartbeats per unit of time, usually per minute.
Time frame: Blood samples will be collected at following time points: Day 1 pre-dose (15 minutes prior to first dose 1), and at Day 2 pre-dose (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6.5, 8, 12, and 24 hours post last dose in each period.
PK parameters include: area under the concentration-time curve from time zero to last time of quantifiable concentration (AUC[0-t]), area under the concentration-time curve from time zero extrapolated to infinite time (AUC[0-infinity]), maximum observed concentration (Cmax), time of occurrence of Cmax (tmax), apparent clearance following oral dosing (CL/F), apparent volume of distribution at steady state after oral administration (Vdz/F), and terminal phase half-life (t1/2) from plasma concentrations of GSK1265744.
Time frame: Blood samples will be collected on Day 2 at pre-dose, 0.5, 1, 2, 3, 4, 6.5, 8, 12, and 24 hours post last dose in each period.
PK parameters include: AUC (0-t), AUC (0-infinity), Cmax, tmax, CL/F, Vdz/f, and t1/2.
Time frame: Up to 62 days.
12-lead ECGs will be performed with the subject in a semi-supine position having rested in this position for at least 10 minutes beforehand. ECGs will be obtained using an ECG machine that automatically calculates the QTcF, QTcB, QTCi, QT, QRS, PR intervals and HR.
Time frame: Up to 62 days.
Vital sign measurement include: blood pressure and heart rate.
Time frame: Up to 62 days.
AEs will be collected from the start of Study Treatment and until the follow-up contact.
Time frame: Up to 62 days.
Clinical laboratory assessment include: hematology, clinical chemistry, urinalysis and additional parameters as needed.
Time frame: Baseline on Day -1 and Day 2 for Periods 1 - 3 (49 Days).
Single ECGs will be obtained at all timepoints during the study using an ECG machine that automatically calculates the QTcF, QTcB, and QTCi intervals.
Time frame: Baseline on Day -1 and Day 2 for Periods 1 - 3 (49 Days).
Difference between GSK12657744 and placebo in terms of change from baseline in QTcF, QTcB and QTci will be measured to characterize pharmacodynamic (PD) relationship between exposure of GSK1265744 and changes in QTcF, QTcB and QTci
Time frame: Blood samples will be collected at following time points: Day 1 pre-dose (15 minutes prior to first dose 1), and at Day 2 pre-dose (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6.5, 8, 12, and 24 hours post last dose in each period.
Plasma concentration profile of GSK1265744 will be assessed to characterize PK/PD relationship between exposure of GSK1265744 and changes in QTcF, QTcB and QTci. PK parameters to be assessed for plasma concentration profile are: area under the concentration-time curve from zero to 24 hours (AUC [0-24]), AUC (0-t), AUC (0-infinity), and Cmax.
ViiV Healthcare
Industry
A Study to Evaluate the Effect of GSK1265744 150mg Administered Orally Every 12h x 3 Doses on Cardiac Conduction as Assessed by 12-lead Electrocardiogram Compared to Placebo and a Single Oral Dose of Moxifloxacin
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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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