Study to Compare Pharmacokinetics & Pharmacodynamics of Warfarin & Esmolol in the Absence & Presence of MEDI0382

Maximum international normalized ratio (INRmax)

Time frame · Days 2-8 and Days 27-33

To assess the INR max in the absence and presence of Warfarin on a steady state MEDI0382

Change in heart rate from resting after a 9-minute excercise treadmill test (Bruce Protocol, first 3 stages)

Time frame · Days 1 and 26

To assess the effects of MEDI0382 on the hear rate-lowering effect of esmolol during treadmill test.

Maximum international normalized ratio (INRmax)

Time frame · Days 2-8 and Days 27-33

To assess the AUC INR in the absence and presence of Warfarin on a steady state MEDI0382

PK(AUC) of R-Warfarin and S-Warfarin

Time frame · Days 2 and 27

To assess AUC of R-warfarin and S-warfarin in the presence and absence of steady state MEDI0382

PK (Cmax) of R-Warfarin and S-Warfarin

Time frame · Days 2 and 27

To assess Cmax of R-warfarin and S-warfarin in the presence and absence of steady state MEDI0382

Number of patients with Adverse Events (AEs)

Time frame · 33 Days

To assess the adverse events as a criteria of safety and tolerability variables.

12 lead electrocardiogram including RR, PR, QRS, QT and QTc intervals

Time frame · Day 1, Day 8, Day 13, and Day 18

To assess the cardiovascular system functioning as a criteria of safety and tolerability variables.

Anti-drug antibody titer incidence

Time frame · Days 1 and 33

To evaluate the safety and tolerability of multiple doses of MEDI0382 in conjunction with Warfarin and Esmolol.

Clinical laboratory assessments (hematology)

Time frame · Days 1 and 33

To assess hematology as a criteria of safety and tolerability variables..

Vital signs (systolic and diastolic blood pressure)

Time frame · Days 1-8, Days 12 and 13, Days 25-33

To assess the vital signs as a criteria of safety and tolerability variables

Vital signs (pulse rate and respiratory rate

Time frame · Days 1-8, Days 12 and 13, Days 25-33

To assess the vital signs as a criteria of safety and tolerability variables

Clinical laboratory assessments (serum chemistry)

Time frame · Day -1, Day 8, Day 17, Day 25 and Day 33

To assess clinical chemistry as a criteria of safety and tolerability variables.

Clinical laboratory assessment (urinalysis)

Time frame · Day -1

To assess urinalysis as a criteria of safety and tolerability variables.