Intravenous administration in humans of single bolus doses of Abciximab from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function as measured by ex vivo platelet aggregation in response to adenosine diphosphate (ADP) or by prolongation of bleeding time. At the two highest doses (0.25 and 0.30 mg/kg) at two hours post injection (the first time point evaluated), over 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation in response to 20 µM ADP was almost abolished. The median bleeding time increased to over 30 minutes at both doses compared with a baseline value of approximately five minutes.

Intravenous administration in humans of a single bolus dose of 0.25 mg/kg followed by a continuous infusion of 10 µg/min for periods of 12 to 96 hours produced sustained high-grade GPIIb/IIIa receptor blockade ( ≥ 80%) and inhibition of platelet function (ex vivo platelet aggregation in response to 5 µM or 20 µM ADP less than 20% of baseline and bleeding time greater than 30 minutes) for the duration of the infusion in most patients. Similar results were obtained when a weight-adjusted infusion dose (0.125 µg/kg/min to a maximum of 10 µg/min) was used in patients weighing up to 80 kg. Results in patients who received the 0.25 mg/kg bolus followed by a 5 µg/min infusion for 24 hours showed a similar initial receptor blockade and inhibition of platelet aggregation, but the response was not maintained throughout the infusion period. The onset of Abciximab-mediated platelet inhibition following a 0.25 mg/kg bolus and 0.125 µg/kg/min infusion was rapid and platelet aggregation was reduced to less than 20% of baseline in 8 of 10 patients at 10 minutes after treatment initiation.

Low levels of GPIIb/IIIa receptor blockade are present for more than 10 days following cessation of the infusion. After discontinuation of Abciximab infusion, platelet function returns gradually to normal. Bleeding time returned to ≤ 12 minutes within 12 hours following the end of infusion in 15 of 20 patients (75%), and within 24 hours in 18 of 20 patients (90%). Ex vivo platelet aggregation in response to 5 µM ADP returned to ≥ 50% of baseline within 24 hours following the end of infusion in 11 of 32 patients (34%) and within 48 hours in 23 of 32 patients (72%). In response to 20 µM ADP, ex vivo platelet aggregation returned to ≥ 50% of baseline within 24 hours in 20 of 32 patients (62%) and within 48 hours in 28 of 32 patients (88%).

Clinical Studies

Abciximab has been studied in four Phase 3 clinical trials, all of which evaluated the effect of Abciximab in patients undergoing percutaneous coronary intervention (PCI): in patients at high risk for abrupt closure of the treated coronary vessel (EPIC), in a broader group of patients (EPILOG), in unstable angina patients not responding to conventional medical therapy (CAPTURE), and in patients suitable for either conventional angioplasty/atherectomy or primary stent implantation (EPILOG Stent; EPISTENT). Percutaneous intervention included balloon angioplasty, atherectomy, or stent placement. All trials involved the use of various, concomitant heparin dose regimens and, unless contraindicated, aspirin (325 mg) was administered orally two hours prior to the planned procedure and then once daily.

EPIC was a multicenter, double-blind, placebo-controlled trial of Abciximab in patients undergoing percutaneous transluminal coronary angioplasty or atherectomy (PTCA) who were at high risk for abrupt closure of the treated coronary vessel (7). Patients were allocated to treatment with: 1) Abciximab bolus plus infusion for 12 hours; 2) Abciximab bolus plus placebo infusion, or; 3) placebo bolus plus infusion. All patients received concomitant heparin (10,000 to 12,000 U bolus followed by an infusion for 12 hours).

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