Efficacy and Safety of TAK-442 in Subjects Undergoing Total Knee Replacement

• Status: Completed
• Trial end date: 2008-10-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to determine if TAK-442, once daily (QD) or twice daily (BID), is as safe and effective as enoxaparin in preventing the development of blood clots after knee replacement surgery.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Takeda
• Treatments: 1-(1-(3-((6-chloronaphthalen-2-yl)sulfonyl)-2-hydroxypropanoyl)piperidin-4-yl)tetrahydropyrimidin-2(1H)-one; Enoxaparin

Criteria

Inclusion Criteria

• Scheduled to undergo elective, unilateral, primary, total knee replacement.

• Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.

• Screening laboratory tests (including clinical chemistry, hematology, and complete urinalysis) are within the reference range for the testing laboratory or are determined not to compromise subject safety by the investigator.

Exclusion Criteria

• Received TAK-442 in a previous clinical study or as a therapeutic agent.

• Body weight greater than 150 kg.

• Known bleeding diathesis (including Von Willebrand's disease or Hemophilia A or B).

• History of intracerebral, intraocular, or gastrointestinal bleeding, or active gastric or duodenal ulceration, within the 6 months prior to Randomization.

• Is required to take or continues taking any disallowed medication, prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including throughout the treatment period of the study due to an increased risk of bleeding, and should be stopped at least 5 days prior to surgery and in accordance with the product information:

• Parenteral anticoagulants

• Unfractionated heparin

• Low molecular weight heparin (eg, dalteparin, non-study enoxaparin)

• Direct thrombin inhibitors (eg, bivalirudin, argatroban)

• Factor Xa inhibitors (eg, fondaparinux)

• Oral anticoagulants

• Warfarin

• Anisindione

• Antiplatelet drugs

• Aspirin greater than 162 mg/day

• Clopidogrel

• Ticlopidine

• Cilostazol

• Dipyridamole

• Glycoprotein IIb/IIIa inhibitors (eg, abciximab, eptifibatide)

• NSAIDs with a half life greater than or equal to 17 hours

• Meloxicam

• Fibrinolytic agents

• tPA (alteplase, reteplase, tenecteplase)

• History of major surgery within 3 months prior to randomization; or deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular accident, or transient ischemic attack within 6 months prior to randomization.

• History of hypersensitivity or allergies to other activated factor X inhibitors or enoxaparin (or other low molecular weight heparins).

• Condition prohibiting bilateral venography.

• Has had multiple or traumatic epidural or spinal punctures immediately prior to randomization (defined as grossly bloody or greater than 3 attempted cannulations).

• Requires use of an indwelling epidural catheter for post-operative analgesia.

• Severe hypertension defined as systolic blood pressure greater than 180 mmHg or diastolic blood pressure greater than 110 mmHg at Screening.

• Moderate to severe renal dysfunction or disease (based on calculated creatinine clearance less than 45 mL/min/1.73 m2) at Screening.

• Alanine aminotransferase level greater than 2.0 times the upper limit of normal, active liver disease, or jaundice at Screening.

• Anemia (hemoglobin less than 10.0 g per dL) or thrombocytopenia (platelet count less than 100 times 103 per uL) at screening.

• Taking aspirin greater than 162 mg per day.

• Abuses drugs (defined as any illicit drug use) or alcohol.

• History of cancer that has not been in remission for at least 5 years prior to the first dose of study drug. (This criterion does not include those subjects with basal cell or Stage 1 squamous cell carcinoma of the skin.)

• Currently participating in another investigational study or has participated in an investigational study within 30 days prior to Screening.

• Any other serious disease or condition at Screening or Randomization that would compromise subject safety or make it difficult to successfully manage and follow the subject according to the protocol.

• Requires the use of pneumatic compression post-operatively.

• Known inherited thrombophilic disorder such as the factor V Leiden or prothrombin gene mutations or deficiencies of antithrombin, protein C, or protein S.