Factor IX Inhibition in Thrombosis Prevention (The FIXIT Trial)

A Multi-Center, Placebo-Controlled Evaluation of the Safety and Efficacy of Three Weeks Extended VTE Prophylaxis With Daily Oral Doses of TTP889 After One Week of Standard Prophylactic Treatment Following Hip Fracture Surgery

The purpose of this study is to determine whether TTP889 prevents venous thromboembolism following surgery to repair hip fracture.

FIXIT is the first Phase 2 study of TTP889. The trial is a proof-of-concept study to determine the safety and antithrombotic efficacy of TTP889 in patients at risk for venous thromboembolism (VTE). The study is a multi-center, randomized, double-blind, parallel-group evaluation of 300 mg TTP889 or placebo, administered orally once daily for three weeks, in patients who have undergone surgery to repair unilateral fracture of the upper third of either femur and who have completed 5 to 9 days of postoperative prophylactic treatment for VTE.

Inclusion Criteria:

• Must have undergone reparative surgery within 72 hours after unilateral hip fracture, defined as fracture of the upper third of either femur
• Must have started standard prophylactic treatment for VTE with low molecular weight heparin (LMWH) or heparin before surgery or within 24 hours after hip fracture surgery, and continued treatment with LMWH or heparin for at least five days, but not more than nine days, after surgery
• Last dose of LMWH or heparin must have been administered at least 12 hours, but not more than 48 hours, before dosing with study drug
• Females must have a negative serum pregnancy test
• Must weigh at least 45 kg
• Must demonstrate the mental and physical ability and willingness to follow all study-specific instructions
• Must be able to read, comprehend and sign the Ethics Committee-approved informed consent form

Exclusion Criteria:

• Evidence of active bleeding
• Clinical signs of VTE
• Any medical requirement for (or intention to use) continued anticoagulation after randomization through the end of study
• History of intracranial bleeding, hemorrhagic stroke, or gastrointestinal bleeding within 3 months of study start
• Presence of active malignant disease
• Hip fracture associated with multiple trauma, that places patient at excessive risk for hemorrhage or organ system failure, or that may make it difficult or impossible to perform bilateral lower limb venography
• Intention to take aspirin at doses greater than 325 mg/day
• Hemoglobin < 5.45 mmol/L (9 g/dL), hematocrit < 29%, or a platelet count < 100,000/mL at the screening visit
• Elevated ALT or AST level > 3.0 times the ULN, or an elevated total bilirubin > 1.5 the ULN at the screening visit
• Creatinine > 180 mmol/L (2.0 mg/dL) at the screening visit
• Any other laboratory value at screening that the Investigator considers to be clinically significant and warrants exclusion from the study
• Patient is currently breast feeding a child and wishes to continue breast feeding
• Previous allergy to contrast material or any other contraindications to perform bilateral lower limb venography
• The use of another investigational drug within 28 days of study entry