This is a Phase I, randomized, double-blind, placebo-controlled, study to estimate the effects of daily oral dosing of 800 mg pazopanib on electrocardiographic parameters (QTc interval duration) as compared with placebo in subjects with solid tumors. Moxifloxacin, will serve as a positive control.
This is a Phase I, randomized, double-blind, placebo-controlled, parallel group study designed to estimate the effects of repeated, once daily oral dosing of pazopanib on electrocardiographic parameters with a particular focus on its effect on cardiac repolarization (QTc interval duration) as compared with placebo in subjects with solid tumors. Moxifloxacin, a drug known to cause mild QTc interval prolongation, is included as a positive control to validate the ability of the study to detect a small prolongation in the QTc interval. Digital 12-lead electrocardiograms (ECGs) will be extracted from continuous ECG recordings obtained via a Holter monitor. The effects of pazopanib and moxifloxacin on cardiac repolarization will be compared with placebo. This study will also assess the pharmacokinetic-pharmacodynamic relationship between plasma concentrations of pazopanib and its metabolites and their effects, if any, on cardiac repolarization, specifically on the QT interval.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
2
Subjects treated with pazopanib
Control for comparison with pazopanib
Comparator for pazopanib
GSK Investigational Site
Duarte, California, United States
GSK Investigational Site
Santa Monica, California, United States
GSK Investigational Site
Detroit, Michigan, United States
GSK Investigational Site
Lebanon, New Hampshire, United States
Change from baseline in QTcF interval at each time point on Study Day 9 (average of at least 3 Holter ECG replicates per time point) as compared with time-matched placebo.
Time frame: 11 days
ECG parameters: RR interval, QT, QTcB, heart rate, PR, QRS intervals and morphology.
Time frame: 11 days
Plasma pazopanib and metabolites (GSK1268992, GSK1268997 and GSK1071306) concentrations and PK parameters AUC(0-t), AUC(0-24), C24 Cmax and tmax as data permit.
Time frame: 11 days
Change from baseline in QTcF interval at each time point on Study Day 1 (average of at least 3 Holter ECG replicates per time point) as compared with time-matched placebo.
Time frame: 11 days
Plasma moxifloxacin concentrations and PK parameters AUC(0-t), AUC(0-∞), Cmax and tmax as data permit.
Time frame: 11 days
Safety parameters: AEs, vital signs, ECGs and clinical laboratory assessments.
Time frame: 11 days
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Placebo for moxifloxacin
GSK Investigational Site
New Brunswick, New Jersey, United States
GSK Investigational Site
Greenville, South Carolina, United States
GSK Investigational Site
Nashville, Tennessee, United States
GSK Investigational Site
Tacoma, Washington, United States