This study is a single dose evaluation using an open label dose escalating design. Cohort1 will consist of 3 healthy male volunteers. Each volunteer will receive a slow IV infusion over 6 hours consisting of saline for 30 minutes (run in period), 8 mcg/h GW328267X for 1.5 hours (total dose of 12mcg) and 10 mcg/h GW328267X for 4 hours (total dose of 40 mcg). Subjects will have continuous cardiac monitoring throughout the dosing period and up to 2 hours after cessation of the intravenous infusion. PK measurements and measurement of erythropoietin and platelet activation will also be done. Samples for PK will be taken at 30 minute intervals during the infusion of GW328267X up to and including 1 hour after cessation of the intravenous infusion. Samples for erythropoietin and platelet aggregation will be done. Cohort 2 is optional and may be carried out in the event that the dose of GW328267X given in Cohort 1 is both well tolerated and subjects do not meet the stopping criteria. The decision to proceed to Cohort 2 and the dose level will be made by the GSK Study Team and the Investigator based on safety, tolerability and preliminary PK/PD data obtained in Cohort 1. It is planned that the maximum total dose given to any subject will not exceed 150mcg. Cohort 2 will consist of 3 healthy male volunteers and the study procedures for this additional Cohort will be the same as that described for Cohort 1.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
3
30mins run-in period
8 mcg/h for 1.5 hours (total dose of 12mcg)
10 mcg/h for 4 hours (total dose of 40 mcg)
GSK Investigational Site
Cambridge, United Kingdom
Safety and tolerability including number of subjects with adverse events assessment
Time frame: baseline, Day 1, Day 2 and Day 10
Safety and tolerability including change from baseline and number subjects with abnormal clinical safety laboratory data
Time frame: baseline, Day 1, Day 2 and Day 10
Safety and tolerability, including change from baseline and number of subjects with abnormal ECG assessments
Time frame: baseline, Day 1, Day 2 and Day 10
Safety and tolerability, including change from baseline and number of subjects with abnormal vital signs (blood pressure and heart rate) assessments
Time frame: baseline, Day 1, Day 2 and Day 10
Heart rate changes from baseline during intravenous infusion of GW328267X
Time frame: baseline, Day 1, Day 2 and Day 10
Platelet aggregation parameters
Time frame: Pre-dose, Day 1 5.5 hr, Day 2
Erythropoietin levels
Time frame: Screening, Pre-dose, Day 2, Follow Up
Levels of GW328267X in plasma
Time frame: baseline, Day 1 and Day 2 (24hrs)
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