Clinical trial NCT00677053: Safety and Efficacy of TAK-442 in Subjects With Acute Coronary Syndromes
Official title: A Phase 2, Double-blind, Randomized, Placebo-controlled Study of the Safety and Efficacy of TAK-442 in Subjects With Acute Coronary Syndromes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Coronary Syndrome
Keywords: Unstable Angina
Myocardial Infarction
Thrombolysis
Anticoagulant
Acute Coronary Syndrome
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2008-05-13
Enrollment: 2753
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Incidence of Major Bleeding Events defined by the Thrombolysis in Myocardial Infarction Scale.
timeFrame: On Occurrence (Up to 24 weeks)
Secondary outcomes:
measure: Composite of Cardiovascular Mortality, non-fatal Myocardial Infarction, non-fatal Stroke, or Myocardial Ischemia requiring hospitalization.
timeFrame: Week 24
measure: Cardiovascular Mortality.
timeFrame: Week 24.
measure: Non-fatal Myocardial Infarction.
timeFrame: Week 24.
measure: Non-fatal Stroke.
timeFrame: Week 24.
measure: Myocardial Ischemia requiring hospitalization.
timeFrame: Week 24.
measure: All-cause Mortality.
timeFrame: Week 24.
measure: Hemorrhagic Mortality.
timeFrame: Week 24.
measure: Composite of Cardiovascular death, non-fatal Myocardial Infarction, or Myocardial Ischemia requiring hospitalization.
timeFrame: Week 24.
measure: Composite of Cardiovascular death, non-fatal Myocardial Infarction, or non-fatal Stroke.
timeFrame: Week 24.
measure: Hospitalization for Heart Failure.
timeFrame: Week 24.
measure: Incidence of minor bleeding events defined by the Thrombolysis in Myocardial Infarction Scale.
timeFrame: On Occurrence (Up to 24 weeks).
measure: Incidence of minimal bleeding events defined by the Thrombolysis in Myocardial Infarction Scale.
timeFrame: On Occurrence (Up to 24 weeks).
measure: Incidence of major, clinically significant non-major bleeding AND minor bleeding events as defined by the Secondary Bleeding Scale
timeFrame: On Occurrence (Up to 24 weeks)
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Tucson
country: United States
state: Arizona
city: Newark
country: United States
state: Delaware
city: Washington
country: United States
state: District of Columbia
city: Pensecola
country: United States
state: Florida
city: West Des Moines
country: United States
state: Iowa
city: Salisbury
country: United States
state: Maryland
city: Minneapolis
country: United States
state: Minnesota
city: Cherry Hill
country: United States
state: New Jersey
city: Toledo
country: United States
state: Ohio
city: Sayre
country: United States
state: Pennsylvania
city: Houston
country: United States
state: Texas
city: Victoria
country: United States
state: Texas
city: Layton
country: United States
state: Utah
city: Roanoke
country: United States
state: Virginia
city: Buenos Aires
country: Argentina
city: Bonheiden
country: Belgium
city: Genk
country: Belgium
city: Liège
country: Belgium
city: Porto Algere
country: Brazil
city: Recife
country: Brazil
city: Haskovo
country: Bulgaria
city: Pazardjik
country: Bulgaria
city: Pleven
country: Bulgaria
city: Plovdiv
country: Bulgaria
city: Rouse
country: Bulgaria
city: Silistra
country: Bulgaria
city: Sofia
country: Bulgaria
city: Stara Zagora
country: Bulgaria
city: Varna
country: Bulgaria
city: Sudbury
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Chilliwack
country: Canada
city: Saint-Charles Borromée
country: Canada
city: Vancouver
country: Canada
city: Santiago
country: Chile
city: Temuco
country: Chile
city: Tallinn
country: Estonia
city: Bad Nauheim
country: Germany
city: Langen
country: Germany
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Nyíregyháza
country: Hungary
city: Szeged
country: Hungary
city: Szolnok
country: Hungary
city: Székesfehérvár
country: Hungary
city: Zalaegerszeg
country: Hungary
city: Ahmedabad
country: India
city: Bikaner
country: India
city: Calicut
country: India
city: Indore
country: India
city: Jaipur
country: India
city: Mangalor
country: India
city: Mumbai
country: India
city: Nagpur
country: India
city: New Delhi
country: India
city: Pune
country: India
city: Shimoga
country: India
city: Thrissur
country: India
city: Trivandrum
country: India
city: Vadodara
country: India
city: Busan
country: Korea, Republic of
city: Daegu
country: Korea, Republic of
city: Jeonrabukdo
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Amsterdam
country: Netherlands
city: Den Haag
country: Netherlands
city: Hardenberg
country: Netherlands
city: Hoorn
country: Netherlands
city: Tilburg
country: Netherlands
city: Arequipa
country: Peru
city: Lima
country: Peru
city: Bacau
country: Romania
city: Baia Mare
country: Romania
city: Braila
country: Romania
city: Brasov
country: Romania
city: Bucuresti
country: Romania
city: Cluj-Napoca
country: Romania
city: Suceava
country: Romania
city: Targoviste
country: Romania
city: Barnaul
country: Russian Federation
city: Kemerovo
country: Russian Federation
city: Krasnoyarsk
country: Russian Federation
city: Moscow
country: Russian Federation
city: Novosibirsk
country: Russian Federation
city: Samara
country: Russian Federation
city: Saratov
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Tomsk
country: Russian Federation
city: Tyumen
country: Russian Federation
city: Voronezh
country: Russian Federation
city: Yaroslavl
country: Russian Federation
city: Kamenica
country: Serbia
city: Sremska
country: Serbia
city: Bloemfontein
country: South Africa
city: CapeTown
country: South Africa
city: Goodwood
country: South Africa
city: Johannesburg
country: South Africa
city: Parow
country: South Africa
city: Pinelands
country: South Africa
city: Pretoria
country: South Africa
city: Randburg
country: South Africa
city: Airdrie
country: United Kingdom
state: North Lanarkshire
Study officials:
affiliation: Takeda
name: Executive Medical Director Clinical Science
role: STUDY_DIRECTOR
References: