Efficacy and Safety of TAK-442 in Subjects Undergoing Total Knee Replacement
A Phase 2, Randomized, Active Comparator-Controlled, Dose-Ranging Study to Evaluate the Efficacy and Safety of TAK-442 in Subjects Undergoing Total Knee Replacement
調査の概要
詳細な説明
Takeda Global Research & Development Center, Inc. is developing the compound TAK-442 as a candidate for the secondary prevention of atherothrombotic events in patients with acute coronary syndromes. TAK-442 is an oral inhibitor of activated factor X within the blood coagulation cascade.
Due to its critical role in propagating the coagulation cascade, activated factor X is now considered to be a therapeutic aim in the development of anticoagulant drugs. Therefore activated factor X inhibitors, are among the agents under investigation as treatments for the spectrum of thromboembolic diseases involving either the arterial or the venous system.
Short term anticoagulation is often used for the prevention of venous thromboembolism. Patients undergoing major orthopedic surgery are at particularly high risk of venous thromboembolism after surgery. Consequently, such patients are routinely given anticoagulant medication after surgery. Although parenteral (injectable) drugs, such as enoxaparin or fondaparinux, can be used for this indication, the need for subcutaneous injection is problematic once patients are discharged from hospital. With the push for shorter hospital stays, this issue is of increasing concern. Therefore, there is a need for new oral anticoagulants. Although warfarin can be used for out of hospital prophylaxis, the need for coagulation monitoring and dose adjustments complicates its use. The new oral anticoagulants have the potential to overcome this problem because they can be given in fixed doses without the need for coagulation monitoring.
The purpose of the current study is to evaluate the antithrombotic effect of TAK-442 in patients undergoing elective total knee replacement surgery. This study will be the first TAK-442 trial in patients.
Individuals who want to participate in this study will be required to provide written informed consent. Study participation is anticipated to be approximately 2.25 months. Multiple procedures will occur at each visit which may include fasting, blood collection, urine collection, physical examinations, electrocardiograms and bilateral venogram. Outside of the study center, participants randomized to enoxaparin will be required to administer study medication subcutaneously with a syringe.
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
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Alabama
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Birmingham、Alabama、アメリカ
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Tuscaloosa、Alabama、アメリカ
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Arizona
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Phoenix、Arizona、アメリカ
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Arkansas
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Little Rock、Arkansas、アメリカ
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California
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Bakersfield、California、アメリカ
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Fountain Valley、California、アメリカ
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Long Beach、California、アメリカ
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Montclair、California、アメリカ
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Oceanside、California、アメリカ
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Vista、California、アメリカ
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Yuba City、California、アメリカ
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Colorado
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Aurora、Colorado、アメリカ
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Centennial、Colorado、アメリカ
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Denver、Colorado、アメリカ
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Florida
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Bay Pines、Florida、アメリカ
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Clearwater、Florida、アメリカ
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DeLand、Florida、アメリカ
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Gulf Breeze、Florida、アメリカ
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Hollywood、Florida、アメリカ
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Pinellas Park、Florida、アメリカ
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Tamarac、Florida、アメリカ
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Georgia
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Atlanta、Georgia、アメリカ
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Idaho
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Boise、Idaho、アメリカ
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Meridian、Idaho、アメリカ
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Illinois
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Springfield、Illinois、アメリカ
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Maryland
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Towson、Maryland、アメリカ
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North Carolina
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Charlotte、North Carolina、アメリカ
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Greensboro、North Carolina、アメリカ
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Ohio
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Cincinnati、Ohio、アメリカ
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Oklahoma
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Tulsa、Oklahoma、アメリカ
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Pennsylvania
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Altoona、Pennsylvania、アメリカ
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Johnstown、Pennsylvania、アメリカ
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South Carolina
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Charleston、South Carolina、アメリカ
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Texas
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Dallas、Texas、アメリカ
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Grapenne、Texas、アメリカ
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Lubbock、Texas、アメリカ
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San Antonio、Texas、アメリカ
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Washington
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Spokane、Washington、アメリカ
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Charlottetown、カナダ
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Alberta
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Edmonton、Alberta、カナダ
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Red Deer、Alberta、カナダ
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British Columbia
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Kelowna、British Columbia、カナダ
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Manitoba
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Winnipeg、Manitoba、カナダ
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New Brunswick
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Fredericton、New Brunswick、カナダ
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St. John、New Brunswick、カナダ
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Nova Scotia
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Dartmouth、Nova Scotia、カナダ
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Ontario
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Ajax、Ontario、カナダ
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Burlington、Ontario、カナダ
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Cambridge、Ontario、カナダ
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Chatham、Ontario、カナダ
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Guelph、Ontario、カナダ
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Kitchener、Ontario、カナダ
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Newmarket、Ontario、カナダ
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Niagra Falls、Ontario、カナダ
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Oakville、Ontario、カナダ
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Oshawa、Ontario、カナダ
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Ottawa、Ontario、カナダ
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Sarnia、Ontario、カナダ
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Scarborough、Ontario、カナダ
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St. Catherines、Ontario、カナダ
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Sudbury、Ontario、カナダ
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Thunder Bay、Ontario、カナダ
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Windsor、Ontario、カナダ
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Quebec
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Montreal、Quebec、カナダ
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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.
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:防止
- 割り当て:ランダム化
- 介入モデル:並列代入
- マスキング:4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
---|---|
実験的:TAK-442 40 mg QD
|
TAK-442 40 mg, tablets, orally, once daily for up to 10 days.
TAK-442 80 mg, tablets, orally, once daily for up to 10 days.
TAK-442 10 mg, tablets, orally, twice daily for up to 10 days.
TAK-442 20 mg, tablets, orally, twice daily for up to 10 days.
TAK-442 40mg, tablets, orally, twice daily for up to 10 days.
TAK-442 80 mg, tablets, orally, twice daily for up to 10 days.
|
実験的:TAK-442 80 mg QD
|
TAK-442 40 mg, tablets, orally, once daily for up to 10 days.
TAK-442 80 mg, tablets, orally, once daily for up to 10 days.
TAK-442 10 mg, tablets, orally, twice daily for up to 10 days.
TAK-442 20 mg, tablets, orally, twice daily for up to 10 days.
TAK-442 40mg, tablets, orally, twice daily for up to 10 days.
TAK-442 80 mg, tablets, orally, twice daily for up to 10 days.
|
実験的:TAK-442 10 mg BID
|
TAK-442 40 mg, tablets, orally, once daily for up to 10 days.
TAK-442 80 mg, tablets, orally, once daily for up to 10 days.
TAK-442 10 mg, tablets, orally, twice daily for up to 10 days.
TAK-442 20 mg, tablets, orally, twice daily for up to 10 days.
TAK-442 40mg, tablets, orally, twice daily for up to 10 days.
TAK-442 80 mg, tablets, orally, twice daily for up to 10 days.
|
実験的:TAK-442 20 mg BID
|
TAK-442 40 mg, tablets, orally, once daily for up to 10 days.
TAK-442 80 mg, tablets, orally, once daily for up to 10 days.
TAK-442 10 mg, tablets, orally, twice daily for up to 10 days.
TAK-442 20 mg, tablets, orally, twice daily for up to 10 days.
TAK-442 40mg, tablets, orally, twice daily for up to 10 days.
TAK-442 80 mg, tablets, orally, twice daily for up to 10 days.
|
実験的:TAK-442 40 mg BID
|
TAK-442 40 mg, tablets, orally, once daily for up to 10 days.
TAK-442 80 mg, tablets, orally, once daily for up to 10 days.
TAK-442 10 mg, tablets, orally, twice daily for up to 10 days.
TAK-442 20 mg, tablets, orally, twice daily for up to 10 days.
TAK-442 40mg, tablets, orally, twice daily for up to 10 days.
TAK-442 80 mg, tablets, orally, twice daily for up to 10 days.
|
実験的:TAK-442 80 mg BID
|
TAK-442 40 mg, tablets, orally, once daily for up to 10 days.
TAK-442 80 mg, tablets, orally, once daily for up to 10 days.
TAK-442 10 mg, tablets, orally, twice daily for up to 10 days.
TAK-442 20 mg, tablets, orally, twice daily for up to 10 days.
TAK-442 40mg, tablets, orally, twice daily for up to 10 days.
TAK-442 80 mg, tablets, orally, twice daily for up to 10 days.
|
アクティブコンパレータ:Enoxaparin 30 mg BID
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Enoxaparin 30 mg, syringe, subcutaneous injection, twice daily for up to 10 days.
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この研究は何を測定していますか?
主要な結果の測定
結果測定 |
時間枠 |
---|---|
Composite evaluation of All-Cause Mortality, Symptomatic and Asymptomatic Deep Vein Thrombosis and Symptomatic Pulmonary Embolism.
時間枠:Day 10.
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Day 10.
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Incidence of Major Bleeding.
時間枠:Day 10.
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Day 10.
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二次結果の測定
結果測定 |
時間枠 |
---|---|
Evaluation of Major Venous Thromboembolism (composite of Symptomatic or Asymptomatic Proximal Deep Vein Thrombosis, Symptomatic Objectively Confirmed Pulmonary Embolism, and Venous Thromboembolism-Related Death).
時間枠:Day 10.
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Day 10.
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Evaluation of Symptomatic Venous Thromboembolism.
時間枠:Day 10.
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Day 10.
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Evaluation of Proximal Deep Vein Thrombosis.
時間枠:Day 10.
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Day 10.
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Evaluation of Distal Deep Vein Thrombosis.
時間枠:Day 10.
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Day 10.
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Evaluation of clinically significant Non-Major Bleeding events.
時間枠:Day 10.
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Day 10.
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Evaluation of Minor Bleeding events.
時間枠:Day 10.
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Day 10.
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協力者と研究者
スポンサー
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- TAK-442_201
- U1111-1115-9359 (レジストリ識別子:WHO)
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
TAK-442の臨床試験
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Centre for Addiction and Mental Health完了
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Takeda完了急性冠症候群アメリカ, ベルギー, ドイツ, ブルガリア, インド, 南アフリカ, オランダ, 大韓民国, カナダ, チリ, ペルー, ロシア連邦, アルゼンチン, ハンガリー, ルーマニア, ブラジル, エストニア, セルビア, イギリス
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Takeda終了しました循環器疾患 | 2型糖尿病アメリカ, フランス, ポーランド, ウクライナ, ドイツ, 香港, 台湾, アルゼンチン, イスラエル, メキシコ, ブルガリア, マレーシア, ルーマニア, カナダ, 大韓民国, ニュージーランド, ペルー, エストニア, フィリピン, ロシア連邦, チェコ共和国, ハンガリー, ブラジル, イタリア, イギリス, リトアニア, スロバキア, オーストラリア, 南アフリカ, ラトビア, クロアチア, タイ
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TakedaTakeda Development Center Americas, Inc.終了しました