Study to Determine Effective Dosing of Fondaparinux in Obese Persons

The incidence of obesity is growing at an alarming pace and has reached epidemic
proportions. Subjects who are more than 100 pounds over their ideal body weight are
classified as being morbidly obese and are considered to carry a high risk for multiple
chronic medical conditions that impact quality of life and shorten life span. As a result of
obesity, these individuals are also at a higher risk for developing life-threatening blood
clots. Such risk is further elevated with exposure of obese subjects to the stress of
surgery. In fact, the most common cause of death after major surgery in morbidly obese
subjects is the migration of blood clots to the lung and heart. With the current rise in
popularity of weight loss surgery, it has become imperative that we identify a medication
that is safe and effective in preventing the formation of blood clots. Fondaparinux has the
potential for being an effective anti-clotting drug. It is superior to other similar drugs
because it is completely utilized by the body, and has a more predictable action. The
problem, however, is that the recommended doses for fondaparinux were obtained after studies
on lean individuals. This is a fixed dose that is administered universally, regardless of
the size of the subject. Presently, we have no information on what the recommended doses
should be for morbidly obese subjects, who are in the most need for effective anti-clotting
medication. This study will attempt to determine whether a fixed dose or a weight-related
dose is appropriate for morbidly obese subjects, and also investigate the safety of
administering weight-based dosing to these individuals.

Inclusion Criteria:

- Age 19-65 BMI: 35-65 Negative pregnancy test on day of study

Exclusion Criteria:

- Blood Pressure < or = to 160/90 Temperature > 37.5 C (99.5 F) Nursing a baby Positive
pregnancy test on day of study. Medications: History of regular treatment with
anticoagulants or any anti-platelet agents including aspirin and other NSAIDS; use of
aspirin or other NSAIDS within 1 month of study.

Past Medical History:

Cerebrovascular accident (including transient ischemic attacks) within 6 months of study.

Diabetic retinopathy as documented by positive fundoscopy in previous 3 months. Active
peptic ulcer disease, by EGD or Ba meal, within 3 months of study. Known bleeding
disorder. Known thrombophilia History of heparin induced thrombocytopenia. History of
bacterial endocarditis. Known hypersensitivity to fondaparinux. Ulcerative colitis.
History of GI bleeding History of hematuria Recent surgery (in previous 3 months). Recent
trauma - road traffic accident (previous 3 months).

Laboratory Values:

Platelet count < or = to 100,000. Hemoglobin <12g/dl - women or <14g/dl - men. Prothrombin
time > 13s Activated partial thromboplastin time (APTT) > 35s Liver function test
parameters: ALT > 60u/L, AST > 40u/L, γ-GT >85u/L, Alkaline phosphatase >251 u/L or total
bilirubin > 1.3 mg/dl.

Estimated urinary creatinine clearance < 50 mls/min. Hematuria on urine dipstick.