Safety and Efficacy of TAK-442 in Subjects With Acute Coronary Syndromes

NCT ID: NCT00677053

Last Updated: 2016-04-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 2753 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-03-31
• Study Completion Date: 2010-06-30

Brief Summary

The purpose of this study is to determine the safety and tolerability of multiple doses of TAK-442once daily, (QD) or twice daily (BID), in subjects with acute coronary syndrome (unstable angina, myocardial infarction).

Detailed Description

Acute coronary syndrome, including myocardial infarction with or without ST-segment elevation and stable or unstable angina, is acknowledged to represent collectively a major global healthcare problem. Despite existing treatments, the rates of patient mortality, myocardial infarction and hospital readmissions during follow-up remain very high.

Due to its critical role in propagating the blood coagulation cascade, activated factor X now is considered to be a major therapeutic target in the development of novel antithrombotic therapy by blocking thrombin generation and attenuating the formation of fibrin. Therefore, activated factor X inhibitors, exhibiting either indirect or direct modes of action, are among the novel agents under investigation in the treatment of acute coronary syndrome.

This study will evaluate the safety and tolerability of TAK-442 compared with placebo in post-acute coronary syndrome subjects who are also receiving standard antiplatelet and other cardiovascular therapy.

Individuals who want to participate in this study will be required to provide written informed consent. Study participation is anticipated to be approximately 3.5 months. Multiple procedures will occur at each visit which may include fasting, blood collection, urine collection, physical examinations, electrocardiograms and bilateral venogram.

Conditions

Acute Coronary Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

TAK-442 10 mg BID

Added with standard care for recurrent ischemic events.

Group Type: EXPERIMENTAL

TAK-442

Intervention Type: DRUG

Stage I: TAK-442 10 mg, capsules, orally, twice daily and standard care for recurrent ischemic events for up to 24 weeks.

TAK-442 20 mg BID

Added with standard care for recurrent ischemic events

Group Type: EXPERIMENTAL

TAK-442

Intervention Type: DRUG

Stage I: TAK-442 20 mg, capsules, orally, twice daily and standard care for recurrent ischemic events for up to 24 weeks.

TAK-442 40 mg QD

Added with standard care for recurrent ischemic events

Group Type: EXPERIMENTAL

TAK-442

Intervention Type: DRUG

Stage I: TAK-442 40 mg, capsules, orally, once daily and standard care for recurrent ischemic events for up to 24 weeks.

TAK-442 40 mg BID

Added with standard care for recurrent ischemic events

Group Type: EXPERIMENTAL

TAK-442

Intervention Type: DRUG

Stage II: TAK-442 40 mg, capsules, orally, twice daily and standard care for recurrent ischemic events for up to 24 weeks.

TAK-442 80 mg QD

Added with standard care for recurrent ischemic events

Group Type: EXPERIMENTAL

TAK-442

Intervention Type: DRUG

Stage II: TAK-442 80 mg, capsules, orally, once daily and standard care for recurrent ischemic events for up to 24 weeks.

TAK-442 80 mg BID

Added with standard care for recurrent ischemic events

Group Type: EXPERIMENTAL

TAK-442

Intervention Type: DRUG

Stage II: TAK-442 80 mg, capsules, orally, twice daily and standard care for recurrent ischemic events for up to 24 weeks.

TAK-442 160 mg QD

Added with standard care for recurrent ischemic events

Group Type: EXPERIMENTAL

TAK-442

Intervention Type: DRUG

Stage III: TAK-442 160 mg, capsules, orally, once daily and standard care for recurrent ischemic events for up to 24 weeks.

TAK-442 120 mg BID

Added with standard care for recurrent ischemic events

Group Type: EXPERIMENTAL

TAK-442

Intervention Type: DRUG

Stage III: TAK-442 120 mg, capsules, orally, twice daily and standard care for recurrent ischemic events for up to 24 weeks.

Placebo

Added with standard care for recurrent ischemic events

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Stages I, II \& III: TAK-442 placebo-matching capsules, orally, twice daily and standard care for recurrent ischemic events for up to 24 weeks.

Interventions

TAK-442

Stage I: TAK-442 10 mg, capsules, orally, twice daily and standard care for recurrent ischemic events for up to 24 weeks.

Intervention Type: DRUG

TAK-442

Stage I: TAK-442 20 mg, capsules, orally, twice daily and standard care for recurrent ischemic events for up to 24 weeks.

Intervention Type: DRUG

TAK-442

Stage I: TAK-442 40 mg, capsules, orally, once daily and standard care for recurrent ischemic events for up to 24 weeks.

Intervention Type: DRUG

TAK-442

Stage II: TAK-442 40 mg, capsules, orally, twice daily and standard care for recurrent ischemic events for up to 24 weeks.

Intervention Type: DRUG

TAK-442

Stage II: TAK-442 80 mg, capsules, orally, once daily and standard care for recurrent ischemic events for up to 24 weeks.

Intervention Type: DRUG

TAK-442

Stage II: TAK-442 80 mg, capsules, orally, twice daily and standard care for recurrent ischemic events for up to 24 weeks.

Intervention Type: DRUG

TAK-442

Stage III: TAK-442 160 mg, capsules, orally, once daily and standard care for recurrent ischemic events for up to 24 weeks.

Intervention Type: DRUG

TAK-442

Stage III: TAK-442 120 mg, capsules, orally, twice daily and standard care for recurrent ischemic events for up to 24 weeks.

Intervention Type: DRUG

Placebo

Stages I, II \& III: TAK-442 placebo-matching capsules, orally, twice daily and standard care for recurrent ischemic events for up to 24 weeks.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Has been hospitalized for acute coronary syndrome
• Is able to initiate study drug if:

• The index event occurred within the past 7 days (the date of initial hospitalization will be utilized for the date on which the index event occurred), and
• The final acute medical or cardiac procedural intervention for the treatment of acute coronary syndrome was last administered or performed at least 36 hours before administration of the first dose of study drug.
• Has at least 1 of the following additional ischemic risk factors:

• Previous myocardial infarction.
• The index event was an anterior myocardial infarction.
• Presence of multivessel coronary disease
• Left bundle branch block.
• Left ventricular ejection fraction less than 40% at any time during hospitalization for the index event.
• Killip class greater than or equal to II at any time during hospitalization for the index event.
• History of symptomatic congestive heart failure
• History of ischemic stroke or transient ischemic attack.
• Presence of peripheral arterial obstructive disease.
• Diabetes mellitus requiring medical therapy to maintain glycemic control.
• Current smoker
• Moderate renal impairment
• 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.

Exclusion Criteria

• Has low body weight greater than 50 kg.
• Has severe hypertension.
• Has a known bleeding/clotting disorder.
• Has acute pericarditis.
• Has a history of intracranial or intraocular bleeding.
• Has a history of gastrointestinal bleeding or gastric or duodenal ulceration.
• Has a history of ischemic stroke or transient ischemic attack.
• Has had major surgery, including coronary artery bypass graft or has undergone non-major laparoscopic surgery or non-major minimally invasive surgery, within 2 weeks prior to Randomization.
• Has a history of cancer that has not been in remission for at least 5 years.
• Has a condition for which long-term anticoagulation therapy is indicated or requires ongoing use of other excluded medications.
• Has severe renal dysfunction.
• Has anemia or thrombocytopenia that has not resolved prior to Randomization.
• Has alanine aminotransferase or total bilirubin levels greater than 2 times the upper limit of normal, active liver disease or jaundice.
• Has a history of illicit drug use or excessive alcohol intake.
• Has any other serious disease or condition that would compromise subject safety, increase the risk of bleeding, or make it difficult to successfully manage and follow the subject according to the protocol.
• Has received TAK-442 in a previous clinical study or as a therapeutic agent.
• Has a history of hypersensitivity or allergies to other fXa inhibitors.
• Has received any investigational compound within 30 days prior to Screening or is currently participating in another study which entails the administration of an investigational or marketed drug, supplement or intervention including, but not limited to diet, exercise, lifestyle or invasive procedure.
• Is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:

• azole antifungal agents
• cyclosporine
• clarithromycin
• HIV protease inhibitors
• nefazodone
• ritonavir
• quinidine
• amiodarone
• verapamil

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Executive Medical Director Clinical Science

Role: STUDY_DIRECTOR

Takeda

Locations

Birmingham, Alabama, United States

Tucson, Arizona, United States

Newark, Delaware, United States

Washington D.C., District of Columbia, United States

Pensecola, Florida, United States

West Des Moines, Iowa, United States

Salisbury, Maryland, United States

Minneapolis, Minnesota, United States

Cherry Hill, New Jersey, United States

Toledo, Ohio, United States

Sayre, Pennsylvania, United States

Houston, Texas, United States

Victoria, Texas, United States

Layton, Utah, United States

Roanoke, Virginia, United States

Buenos Aires, , Argentina

Bonheiden, , Belgium

Genk, , Belgium

Liège, , Belgium

Porto Algere, , Brazil

Recife, , Brazil

Haskovo, , Bulgaria

Pazardzhik, , Bulgaria

Pleven, , Bulgaria

Plovdiv, , Bulgaria

Rousse, , Bulgaria

Silistra, , Bulgaria

Sofia, , Bulgaria

Stara Zagora, , Bulgaria

Varna, , Bulgaria

Greater Sudbury, Ontario, Canada

Toronto, Ontario, Canada

Chilliwack, , Canada

Saint-Charles-Borromée, , Canada

Vancouver, , Canada

Santiago, , Chile

Temuco, , Chile

Tallinn, , Estonia

Bad Nauheim, , Germany

Langen, , Germany

Budapest, , Hungary

Debrecen, , Hungary

Nyíregyháza, , Hungary

Szeged, , Hungary

Székesfehérvár, , Hungary

Szolnok, , Hungary

Zalaegerszeg, , Hungary

Ahmedabad, , India

Bikaner, , India

Calicut, , India

Indore, , India

Jaipur, , India

Mangaluru, , India

Mumbai, , India

Nagpur, , India

New Delhi, , India

Pune, , India

Shimoga, , India

Thrissur, , India

Trivandrum, , India

Vadodara, , India

Amsterdam, , Netherlands

Hardenberg, , Netherlands

Hoorn, , Netherlands

The Hague, , Netherlands

Tilburg, , Netherlands

Arequipa, , Peru

Lima, , Peru

Bacau, , Romania

Baia Mare, , Romania

Brasov, , Romania

Brăila, , Romania

Bucharest, , Romania

Cluj-Napoca, , Romania

Suceava, , Romania

Târgovişte, , Romania

Barnaul, , Russia

Kemerovo, , Russia

Krasnoyarsk, , Russia

Moscow, , Russia

Novosibirsk, , Russia

Saint Petersburg, , Russia

Samara, , Russia

Saratov, , Russia

Tomsk, , Russia

Tyumen, , Russia

Voronezh, , Russia

Yaroslavl, , Russia

Kamenica, , Serbia

Sremska, , Serbia

Bloemfontein, , South Africa

CapeTown, , South Africa

Goodwood, , South Africa

Johannesburg, , South Africa

Parow, , South Africa

Pinelands, , South Africa

Pretoria, , South Africa

Randburg, , South Africa

Busan, , South Korea

Daegu, , South Korea

Jeonrabukdo, , South Korea

Seoul, , South Korea

Airdrie, North Lanarkshire, United Kingdom

Countries

United States; Argentina; Belgium; Brazil; Bulgaria; Canada; Chile; Estonia; Germany; Hungary; India; Netherlands; Peru; Romania; Russia; Serbia; South Africa; South Korea; United Kingdom

Other Identifiers

U1111-1112-5867

Identifier Type: REGISTRY

Identifier Source: secondary_id

TAK-442_202

Identifier Type: -

Identifier Source: org_study_id