This study is a randomized, double-blind, ascending dose, placebo-controlled, incomplete crossover, single and multiple dose study in healthy Japanese male subjects to assess the pharmacokinetics and safety/tolerability of single and multiple intravenous administration of GR121167. Serial blood samples and pooled urine samples for the determination of GR121167 concentration will be collected and safety assessments will be performed for each treatment period. The pharmacokinetics and dose proportionality of GR121167 after single intravenous administration of GR121167 at the dose levels of 100 mg, 300 mg and 600 mg will be assessed. In addition, in the final treatment period (600 mg), twice daily intravenous administrations for 5 days will be also conducted and the pharmacokinetics and accumulation will be assessed.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
18
GR121167 solution will be administered intravenously. For 100 mg subject will receive 10 milliliter (mL) of solution, 30 mL for 300 mg and 60 mL for 600 mg
Placebo solution will be administered intravenously.
GSK Investigational Site
Tokyo, Japan
Profile of pharmacokinetics
Cmax, AUC0-inf, AUC0-last, AUC0-12, C12 (Cτ), accumulation ratios (Ro, Rs)
Time frame: Pre, 0.5, 0.75, 1, 1.5, 2, 4, 6 ,8 ,10 ,12 ,24 hrs after single dose and 5 days multiple dose, and at the trough during multiple doses
Safety parameters
vital signs, ECGs, clinical laboratory tests, and adverse events
Time frame: upto 24 hrs after dose and 7 days after final dose
Profile of urinary pharmacokinetics
Ae, fe, CLr
Time frame: 0-4, 4-8, 8-12, 12-24hrs after single dose
Profile of serum pharmacokinetics
AUC0-24, %AUCex, λz, tmax, t1/2, CL, Vz, Vss
Time frame: Pre, 0.5, 0.75, 1, 1.5, 2, 4, 6 ,8 ,10 ,12 ,24 hrs after single dose and 5 days multiple dose
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