This will be a randomized, single-blind, placebo controlled, parallel group study. Approximately 260 subjects will be enrolled in five groups. This study is designed to compare the effects of tafenoquine, administered as single dose as well as administered over three consecutive days, on the changes in QT duration to those observed in subjects dosed with either moxifloxacin or placebo.
SB-252263 (tafenoquine, TQ) is a new 8-aminoquinoline antimalarial drug being developed by GlaxoSmithKline (GSK) and the Medicines for Malaria Venture with the assistance and historical support of the Walter Reed Army Institute of Research. Tafenoquine has been shown to be effective in the treatment of plasmodial infections in vitro, in pre-clinical models in vivo, and during early phase clinical studies for radical cure and eradication of liver hypnozoites in patients infected with Plasmodium vivax. This study is designed to compare the effects of tafenoquine mono-therapy, administered as a single dose or administered on 3 consecutive days, on the changes in QT duration to those observed in subjects dosed with either Avelox (moxifloxacin hydrochloride) or placebo. This will be a randomized, single-blind, placebo controlled, parallel group study. Parallel group design is chosen because tafenoquine has a long half-life, about 14 to 19 days, and therefore a cross-over design is not a practical alternative. Moxifloxacin will be used as a positive control in order to validate the sensitivity of the study in detecting QTc change. Moxifloxacin has been shown to prolong the QT interval in a dose-dependent manner in patients and healthy volunteers, and the QTc prolongation has been well quantified.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
SINGLE
Enrollment
260
Single dose of Tafenoquine give on Day 3 only
Single dose of Tafenoquine given on Day 3 only
400mg Dose of Tafenoquine given on each of the three consecutive dosing days
GSK Investigational Site
Culver City, California, United States
GSK Investigational Site
Baltimore, Maryland, United States
Change from baseline in QTcF for 1200 mg dose of tafenoquine compared to baseline
Contineous QTcF will be electronically recorded using holtor monitors. The primary comparison of interest is the mean time-matched change from baseline in QTcF for the difference tafenoquine-placebo for 1200mg dose of tafenoquine at each timepoint.
Time frame: Day 1, Day 2, day 3, Day 4, Day 5 and Day 6
Change from Baseline in QTcB, QTcI, QT, and HR for 1200mg dose of tafenoquine
electronic ECGs collected using holter monitors will be analysed to measure QTcF QTcB, QTcI, QT, and Heart Rate (HR)
Time frame: Day 1, Day 2, day 3, Day 4, Day 5 and Day 6
Change from Baseline in QTcF QTcB, QTcI, QT, and HR for 300 mg single dose of tafenoquine
electronic ECGs collected using holter monitors will be analysed to measure QTcF QTcB, QTcI, QT, and Heart Rate (HR)
Time frame: Day 1, Day 2, day 3, Day 4, Day 5 and Day 6
Change from Baseline in QTcF, QTcB, QTcI, QT, and HR for placebo
electronic ECGs collected using holter monitors will be analysed to measure QTcF QTcB, QTcI, QT, and Heart Rate (HR)
Time frame: Day 1, Day 2, day 3, Day 4, Day 5 and Day 6
Change from Baseline in QTcF, QTcB, QTcI, QT, and HR for moxifloxacin
electronic ECGs collected using holter monitors will be analysed to measure QTcF QTcB, QTcI, QT, and Heart Rate (HR)
Time frame: Day 1, Day 2, day 3, Day 4, Day 5 and Day 6
Plasma concentrations and derived pharmacokinetic parameters AUC(0-t), Cmax, and tmax of tafenoquine
Blood samples will be collected at pre-dose on Days 1 and 2, and Day 3: pre-dose, 1, 2, 3, 4, 5, 6, 9, 12, 15, 20, 24, 36, 48 and 72 hours post Day 3 dose, to measure plasma concentrations and derived pharmacokinetic parameters AUC(0-t), Cmax, and tmax of tafenoquine
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moxifloxacine given on Day 3 only
Placebo given on all three days to all groups except for group 5 on Day 3
Placebo for moxifloxacin, given to all groups on all days except for Group 3 on Day 3
Time frame: Day 1, Day 2, day 3, Day 4, Day 5 and Day 6
Safety and tolerability of tafenoquine as assessed by 12-lead ECGs, vital signs, adverse events, and clinical laboratory tests
Safety and tolerability of tafenoquine as assessed by 12-lead ECGs, vital signs, adverse events, and clinical laboratory tests
Time frame: Day 1, Day 2 and Day 3
Change from Baseline in QTcF QTcB, QTcI, QT, and HR for 600 mg single dose of tafenoquine
electronic ECGs collected using holter monitors will be analysed to measure QTcF QTcB, QTcI, QT, and Heart Rate (HR)
Time frame: Day 1, Day 2, day 3, Day 4, Day 5 and Day 6
Plasma concentrations and derived pharmacokinetic parameters AUC(0-t), Cmax, and tmax of moxifloxacin
Blood samples will be collected at pre-dose on Days 1 and 2, and Day 3: pre-dose, 1, 2, 3, 4, 5, 6, 9, 12, 15, 20, 24, 36, 48 and 72 hours post Day 3 dose, to measure plasma concentrations and derived pharmacokinetic parameters AUC(0-t), Cmax, and tmax of moxifloxacin
Time frame: Day 1, Day 2, day 3, Day 4, Day 5 and Day 6