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

NCT00641732 | Completed Phase 2 DMC

• 2 other identifiers: TAK-442_201U1111-1115-9359
• Study Type: interventional
• Target: 1,045
• Locations: 2 countries
• Sites: 64

Brief 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.

Conditions

Venous Thromboembolism

Keywords

venous thromboembolism; oral anticoagulant; direct factor Xa inhibitor; total knee replacement; drug therapy

Outcome Measures

Primary Outcomes (2)

• Composite evaluation of All-Cause Mortality, Symptomatic and Asymptomatic Deep Vein Thrombosis and Symptomatic Pulmonary Embolism.

  Day 10.

• Incidence of Major Bleeding.

  Day 10.

Secondary Outcomes (6)

• Evaluation of Major Venous Thromboembolism (composite of Symptomatic or Asymptomatic Proximal Deep Vein Thrombosis, Symptomatic Objectively Confirmed Pulmonary Embolism, and Venous Thromboembolism-Related Death).

  Day 10.

• Evaluation of Symptomatic Venous Thromboembolism.

  Day 10.

• Evaluation of Proximal Deep Vein Thrombosis.

  Day 10.

• Evaluation of Distal Deep Vein Thrombosis.

  Day 10.

• Evaluation of clinically significant Non-Major Bleeding events.

  Day 10.

Study Arms (7)

TAK-442 40 mg QD

EXPERIMENTAL

Drug: TAK-442

TAK-442 80 mg QD

EXPERIMENTAL

Drug: TAK-442

TAK-442 10 mg BID

EXPERIMENTAL

Drug: TAK-442

TAK-442 20 mg BID

EXPERIMENTAL

Drug: TAK-442

TAK-442 40 mg BID

EXPERIMENTAL

Drug: TAK-442

TAK-442 80 mg BID

EXPERIMENTAL

Drug: TAK-442

Enoxaparin 30 mg BID

ACTIVE COMPARATOR

Drug: Enoxaparin

Interventions

TAK-442 DRUG

TAK-442 40 mg, tablets, orally, once daily for up to 10 days.

TAK-442 40 mg QD

Enoxaparin DRUG

Enoxaparin 30 mg, syringe, subcutaneous injection, twice daily for up to 10 days.

Enoxaparin 30 mg BID

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Takeda: lead

Study Sites (64)

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Birmingham, Alabama, United States

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Tuscaloosa, Alabama, United States

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Phoenix, Arizona, United States

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Little Rock, Arkansas, United States

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Bakersfield, California, United States

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Fountain Valley, California, United States

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Long Beach, California, United States

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Montclair, California, United States

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Oceanside, California, United States

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Vista, California, United States

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Yuba City, California, United States

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Aurora, Colorado, United States

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Centennial, Colorado, United States

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Denver, Colorado, United States

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Bay Pines, Florida, United States

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Clearwater, Florida, United States

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DeLand, Florida, United States

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Gulf Breeze, Florida, United States

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Hollywood, Florida, United States

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Pinellas Park, Florida, United States

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Tamarac, Florida, United States

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Atlanta, Georgia, United States

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Boise, Idaho, United States

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Meridian, Idaho, United States

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Springfield, Illinois, United States

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Towson, Maryland, United States

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Charlotte, North Carolina, United States

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Greensboro, North Carolina, United States

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Cincinnati, Ohio, United States

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Tulsa, Oklahoma, United States

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Altoona, Pennsylvania, United States

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Johnstown, Pennsylvania, United States

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Charleston, South Carolina, United States

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Dallas, Texas, United States

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Grapenne, Texas, United States

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Lubbock, Texas, United States

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San Antonio, Texas, United States

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Spokane, Washington, United States

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Edmonton, Alberta, Canada

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Red Deer, Alberta, Canada

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Kelowna, British Columbia, Canada

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Winnipeg, Manitoba, Canada

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Fredericton, New Brunswick, Canada

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Saint John, New Brunswick, Canada

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Dartmouth, Nova Scotia, Canada

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Ajax, Ontario, Canada

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Burlington, Ontario, Canada

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Cambridge, Ontario, Canada

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Chatham, Ontario, Canada

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Greater Sudbury, Ontario, Canada

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Guelph, Ontario, Canada

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Kitchener, Ontario, Canada

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Newmarket, Ontario, Canada

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Niagra Falls, Ontario, Canada

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Oakville, Ontario, Canada

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Oshawa, Ontario, Canada

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Ottawa, Ontario, Canada

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Saint Catherines, Ontario, Canada

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Sarnia, Ontario, Canada

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Scarborough Village, Ontario, Canada

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Thunder Bay, Ontario, Canada

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Windsor, Ontario, Canada

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Montreal, Quebec, Canada

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Charlottetown, Canada

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Related Publications (1)

• Weitz JI, Cao C, Eriksson BI, Fisher W, Kupfer S, Raskob G, Spaeder J, Turpie AG. A dose-finding study with TAK-442, an oral factor Xa inhibitor, in patients undergoing elective total knee replacement surgery. Thromb Haemost. 2010 Dec;104(6):1150-7. doi: 10.1160/TH10-05-0273. Epub 2010 Sep 30.

  PMID: 20886185 RESULT

MeSH Terms

Conditions

Venous Thromboembolism

Interventions

1-(1-(3-((6-chloronaphthalen-2-yl)sulfonyl)-2-hydroxypropanoyl)piperidin-4-yl)tetrahydropyrimidin-2(1H)-one; Enoxaparin

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Executive Medical Director Clinical Science

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2008
• First Posted: March 24, 2008
• Study Start: October 1, 2007
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2008
• Last Updated: April 13, 2016

Record last verified: 2016-03

Locations

US (38); CA (26)