This study is being conducted to test the hypothesis that coadministration of clopidogrel with DS-1040b will be safe and well tolerated. Subjects entering the study will initially receive a single 12 hour infusion of DS-1040b, to generate data on the effect of DS-1040b alone. After a wash-out period (to ensure that no DS-1040b is left in the blood) subjects will receive repeated clopidogrel doses over 5 days to generate data on the effect of clopidogrel alone. On the sixth day subjects will receive both DS-1040b and clopidogrel, and the effects will be compared to when the two treatments were given alone.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
22
20 mg single 12-hour intravenous infusion
Clopidogrel (Plavix) administered orally 300 mg loading dose on Day 1 followed by 75 mg daily on Days 2-5
Hammersmith Medicines Research
London, United Kingdom
number of adverse events
Evaluation of the safety and tolerability of DS-1040 administered alone or with clopidogrel, as determined by adverse events,from the time of dosing up to 5 days postdose.
Time frame: 5 days
physical exam profile
Evaluation of the safety and tolerability of DS-1040 administered alone or with clopidogrel, as determined by physical examination findings, vital signs, 12-lead electrocardiograms (ECGs), clinical safety laboratory tests from the time of dosing up to 5 days postdose.
Time frame: 5 days
bleeding time measurements
Evaluation of the safety and tolerability of DS-1040 administered alone or with clopidogrel, as determined by bleeding time assessments from the time of dosing up to 5 days postdose.
Time frame: 5 days
DS-1040b plasma concentration profile Time of Maximum plasma concentration(Tmax)
Plasma concentrations of DS-1040 and derived PK parameters up to 5 days after a single 20 mg intravenous infusion of DS-1040 (alone and with clopidogrel).
Time frame: 5 days
DS-1040b plasma concentration profile Area Under the plasma concentration time Curve (AUC)
Plasma concentrations of DS-1040 and derived PK parameters up to 5 days after a single 20 mg intravenous infusion of DS-1040 (alone and with clopidogrel).
Time frame: 5 days
DS-1040b plasma concentration profile Maximum plasma concentration (Cmax)
Plasma concentrations of DS-1040 and derived PK parameters up to 5 days after a single 20 mg intravenous infusion of DS-1040 (alone and with clopidogrel).
Time frame: 5 days
changes in pharmacodynamic profile single administration
Change in baseline of pharmacodynamic parameters (thrombin activatable fibrinolysis inhibitor activity, clot lysis, plasma D-dimer, ADP-induced platelet aggregation) up to 5 days after a single 20 mg intravenous infusion of DS-1040 (alone and with clopidogrel).
Time frame: 5 days
clopidogrel plasma concentration profile Tmax
Plasma concentrations of Clopidogrel Active Metabolite and derived PK parameters after repeated Clopidogrel administration (alone and with DS-1040)
Time frame: 5 days
clopidogrel plasma concentration profile AUC
Plasma concentrations of Clopidogrel Active Metabolite and derived PK parameters after repeated Clopidogrel administration (alone and with DS-1040)
Time frame: 5 days
clopidogrel plasma concentration profile Cmax
Plasma concentrations of Clopidogrel Active Metabolite and derived PK parameters after repeated Clopidogrel administration (alone and with DS-1040)
Time frame: 5 days
changes in pharmacodynamic profile repeated administration
Change in baseline of pharmacodynamic parameters (thrombin activatable fibrinolysis inhibitor activity, clot lysis, plasma D-dimer, ADP-induced platelet aggregation) up to 5 days after repeated Clopidogrel administration (alone or with DS-1040)
Time frame: 5 days
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