BMS-562247 in Subjects Undergoing Elective Total Knee Replacement Surgery

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to learn if BMS-562247 can prevent blood clots in the legs and lungs in men and women following unilateral total knee replacement surgery. The safety of this treatment will also be studied.

Official Title
-----------------
A Phase 2 Randomized, Double-Blinded (BMS-562247 and Enoxaparin), Active-Controlled (Enoxaparin and Warfarin), Parallel-Arm, Dose-Response Study of the Oral Factor Xa Inhibitor BMS-562247 in Subjects Undergoing Elective Total Knee Replacement Surgery

Conditions
-----------------
Venous Thrombosis, Pulmonary Embolism

Intervention / Treatment
-----------------
* Drug: Apixaban
* Drug: Enoxaparin
* Drug: Warfarin
* Drug: Enoxaparin Placebo
* Drug: Apixaban Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Undergoing elective unilateral total knee replacement surgery. Willing and able to undergo bilateral ascending contrast venography. Able to inject (by self or caregiver) study medication subcutaneously. Exclusion Criteria: Women of childbearing potential. Women who are pregnant or breastfeeding. Under some conditions, subjects weighing more than 300 lbs. (136kg) and/or Body Mass Index (BMI) >=35 kg/m2

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A1<br>Apixaban: 2.5 mg, BID PLUS Enoxaparin Placebo | Drug: Apixaban<br>* Tablets, Oral, 12 +/- 2 days<br>* Other names: BMS-562247;Drug: Enoxaparin Placebo<br>* Injection, SQ, BID, 12 +/- 2 days<br>|
| Experimental: A2<br>Apixaban: 5 mg, BID PLUS Enoxaparin Placebo | Drug: Apixaban<br>* Tablets, Oral, 12 +/- 2 days<br>* Other names: BMS-562247;Drug: Enoxaparin Placebo<br>* Injection, SQ, BID, 12 +/- 2 days<br>|
| Experimental: A3<br>Apixaban: 10 mg, BID PLUS Enoxaparin Placebo | Drug: Apixaban<br>* Tablets, Oral, 12 +/- 2 days<br>* Other names: BMS-562247;Drug: Enoxaparin Placebo<br>* Injection, SQ, BID, 12 +/- 2 days<br>|
| Experimental: A4<br>Apixaban: 5 mg, QD PLUS Enoxaparin Placebo | Drug: Apixaban<br>* Tablets, Oral, 12 +/- 2 days<br>* Other names: BMS-562247;Drug: Enoxaparin Placebo<br>* Injection, SQ, BID, 12 +/- 2 days<br>|
| Experimental: A5<br>Apixaban: 10 mg, QD PLUS Enoxaparin Placebo | Drug: Apixaban<br>* Tablets, Oral, 12 +/- 2 days<br>* Other names: BMS-562247;Drug: Enoxaparin Placebo<br>* Injection, SQ, BID, 12 +/- 2 days<br>|
| Experimental: A6<br>Apixaban: 20 mg, QD PLUS Enoxaparin Placebo | Drug: Apixaban<br>* Tablets, Oral, 12 +/- 2 days<br>* Other names: BMS-562247;Drug: Enoxaparin Placebo<br>* Injection, SQ, BID, 12 +/- 2 days<br>|
| Active Comparator: E1<br>Enoxaparin: 30 mg PLUS Apixaban Placebo | Drug: Enoxaparin<br>* Injection, SQ, Q12H, 12 +/- 2 days<br>Drug: Apixaban Placebo<br>* Tablets, Oral, BID, 12 +/- 2 days<br>|
| Active Comparator: W1<br>Warfarin: 5 mg tablets dose titrated to a targeted INR of 1.8 to 3.0 | Drug: Warfarin<br>* Tablets, Oral, QD, 12 +/- 2 days<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the dose-response relationship among the 3 QD and 3 BID doses of BMS-562247 on the composite endpoint of adjudicated VTE events and all-cause death in subjects treated with study medication for 12 +/-2 days following surgery |  | throughout the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the effect of QD and BID dose of BMS-562247 vs subcutaneous 30 mg q12h enoxaparin and warfarin on the composite endpoint of adjudication VTE events and all-cause death in subjects treated for 12 +/-2 days following surgery |  | throughout the study | 
| Assess the effect of each QD and BID dose of BMS-562247 versus subcutaneous 30 mg q12h enoxaparin and oral warfarin on the incidence of adjudicated major bleeding events in subjects treated with study medication for 12 +/-2 days following surgery |  | throughout the study | 
| Assess the effect of each QD and BID dose of BMS-562247 versus subcutaneous 30 mg q12h enoxaparin and oral warfarin on the incidence of adjudicated minor bleeding events in subjects treated with study medication for 12 +/-2 days following surgery |  | throughout the study | 
| To determine the pharmacokinetic (PK) profile of BMS-562247 and the relationship to dose and dose schedule |  | throughout the study | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Prevention of deep vein thrombosis and pulmonary embolism, Preventive therapy