TUESDAY 19TH OCTOBER2010

CATH LAB PRESENTATION

TAO /ACS study

STUDY NUMBER: EFC6204

Randomized, double-blind, triple-dummy trial to compare the efficacy of otamixaban with Unfractionated Heparin + eptifibatide, in patients with Unstable angina/Non ST segment Elevation Myocardial infarction scheduled to undergo an early invasive strategy

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Inclusion Criteria

• Patient with non-STE-ACS with ischemic discomfort (ie, ischemic chest pain or equivalent) at rest ≥10 minutes within 24 hours of randomization

and• One of the two following criteria of non-ST elevation ACS:

• New ST-segment depression ≥0.1 mV (≥1 mm), or transient (<30 minutes) ST-segment elevation ≥0.1 mV (≥1 mm) in at least 2 contiguous leads on the ECG,

OR • Elevation of cardiac biomarkers within 24 hours of randomization,

defined as elevated troponin T, troponin I, or CK-MB level above upper limit of normal

and• Planned to have a coronary angiography (followed, when

indicated, by PCI) as early as possible (after at least 2 hours of treatment with study drug) and within 36 hours (at the latest on Day 3, if justified)

and• Informed consent obtained in writing

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Exclusion Criteria

Related to prior or concomitant treatments

Patient having received anticoagulant treatment (including UFH, LMWH, or bivalirudin) for more than 24 hours prior to randomization or who have been treated by fondaparinux or abciximab

Inability to discontinue current anticoagulation in order to transition to Investigational Products according to the specified transition timing

Patients who can not be treated by aspirin and clopidogrel (or any other oral antiplatelet agent) according to their local labeling

Exclusion criteria

Related to eptifibatide

Patient who cannot be treated with eptifibatide according to the national labeling

Related to unfractionated heparin

Patient who cannot be treated with UFH according to the national labeling

Related to otamixaban

Allergy to otamixaban

Otamixaban Characteristics

Specific Factor Xa inhibitor Proximal inhibition of the coagulation cascade

Small molecule, direct inhibitor Allows for inhibition of clot-bound factor Xa, which

is inaccessible to large molecule and indirect inhibitors

Reversible, short initial half-life (20-30 mins) Given as wt-based IV bolus & infusion Eliminated via feces/bile, no significant renal

elimination Permits rapid initiation & d/c of anticoagulation

Discontinued prior anticoagulants

R

IVRS

Signature of ICF

Preparation of study drugs

Administration of study drugs

Transition Timing for Discontinuation of Previous Anticoagulation

Delay between discontinuation open label anticoagulant and study drug:

UFH or bivaluridin 90 - 150 minutes (unless aPTT < 50 sec)

LMWH 8 hours since last injection

Tirofiban or eptifibatide 4 hours

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Triple Dummy Design

Randomized to Otamixaban

OtamixabanPlacebo

UFHPlacebo

Eptifibatide

Randomized to UFH + Eptifibatide

PlaceboOtamixaban

UFH Eptifibatide

Otamixaban/pbo ; UFH/pbo ; and Eptifibatide/pbo

prepared by Pharmacist or Investigator using

study kits

PCI startPCI start

Study Drug Administration A9

If no PCI is performed

Drug A

Drug B: monitoring of APTT (blinded) pre PCI and during PCI: target 1.5-2XN

Randomization

ASA, Clopi , other ADP receptor antagonistAs per label and guidelines

CK MB and Troponin T (or I) : at 8h and 16h post Randomization

Per investigator’s judgment Up to Day 4 maximum

PCI

Drug A

Drug B: monitoring of ACT (blinded) pre PCI and during PCI: target > 200s

Pre PCI PCI start

ASA, Clopi , other ADP receptor antagonistAs per label and guidelines

CK MB and Troponin T (or I) : Pre PCI and at 2h, 8h and 16h post PCI

PCI end

ACT for sheath removal

After PCI

Drug C started immediately before PCI start and continued up to 18-24h post PCI or until hospital discharge

• Within 36h (if possible, 2 hrs after start of study meds), max Day 3 if justified

• Open-label UFH flushes per operator ++++++++• Bail-out eptifibatide if severe Recurrent Ischemia or thromb PCI

complication

TAO /ACS study

Flushing of the catheter with UF : During coronary angiography/PCI: the catheters

must be flushed with heparinized serum saline.

Thrombotic complications during PCI/angio: Consider bailout with eptifibatide (+ check ACT

and give additional Drug B bolus if <225s)

BLINDED ACT / Hemochron Device

Direct Venous Blood Sample• Cannot use “finger sticks”• CAN use “buff caps/heplocks/IV starts”• MUST be downstream from study drug infusion site

Consider femoral vein sheath

Clinical Challenges