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

Purpose

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).

Condition	Intervention	Phase
Acute Coronary Syndrome	Drug: TAK-442 Drug: Placebo	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Angina Coronary Artery Disease Heart Attack

U.S. FDA Resources

Further study details as provided by Takeda:

Primary Outcome Measures:

Incidence of Major Bleeding Events defined by the Thrombolysis in Myocardial Infarction Scale. [ Time Frame: On Occurrence (Up to 24 weeks) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Composite of Cardiovascular Mortality, non-fatal Myocardial Infarction, non-fatal Stroke, or Myocardial Ischemia requiring hospitalization. [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
Cardiovascular Mortality. [ Time Frame: Week 24. ] [ Designated as safety issue: No ]
Non-fatal Myocardial Infarction. [ Time Frame: Week 24. ] [ Designated as safety issue: No ]
Non-fatal Stroke. [ Time Frame: Week 24. ] [ Designated as safety issue: No ]
Myocardial Ischemia requiring hospitalization. [ Time Frame: Week 24. ] [ Designated as safety issue: No ]
All-cause Mortality. [ Time Frame: Week 24. ] [ Designated as safety issue: No ]
Hemorrhagic Mortality. [ Time Frame: Week 24. ] [ Designated as safety issue: No ]
Composite of Cardiovascular death, non-fatal Myocardial Infarction, or Myocardial Ischemia requiring hospitalization. [ Time Frame: Week 24. ] [ Designated as safety issue: No ]
Composite of Cardiovascular death, non-fatal Myocardial Infarction, or non-fatal Stroke. [ Time Frame: Week 24. ] [ Designated as safety issue: No ]
Hospitalization for Heart Failure. [ Time Frame: Week 24. ] [ Designated as safety issue: Yes ]
Incidence of minor bleeding events defined by the Thrombolysis in Myocardial Infarction Scale. [ Time Frame: On Occurrence (Up to 24 weeks). ] [ Designated as safety issue: Yes ]
Incidence of minimal bleeding events defined by the Thrombolysis in Myocardial Infarction Scale. [ Time Frame: On Occurrence (Up to 24 weeks). ] [ Designated as safety issue: Yes ]
Incidence of major, clinically significant non-major bleeding AND minor bleeding events as defined by the Secondary Bleeding Scale [ Time Frame: On Occurrence (Up to 24 weeks) ] [ Designated as safety issue: Yes ]

Enrollment:	2753
Study Start Date:	March 2008
Study Completion Date:	June 2010
Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: TAK-442 10 mg BID Added with standard care for recurrent ischemic events.	Drug: TAK-442 Stage I: TAK-442 10 mg, capsules, orally, twice daily and standard care for recurrent ischemic events for up to 24 weeks.
Experimental: TAK-442 20 mg BID Added with standard care for recurrent ischemic events	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.
Experimental: TAK-442 40 mg QD Added with standard care for recurrent ischemic events	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.
Experimental: TAK-442 40 mg BID Added with standard care for recurrent ischemic events	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.
Experimental: TAK-442 80 mg QD Added with standard care for recurrent ischemic events	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.
Experimental: TAK-442 80 mg BID Added with standard care for recurrent ischemic events	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.
Experimental: TAK-442 160 mg QD Added with standard care for recurrent ischemic events	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.
Experimental: TAK-442 120 mg BID Added with standard care for recurrent ischemic events	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.
Placebo Comparator: Placebo Added with standard care for recurrent ischemic events	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.

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

Ages Eligible for Study:	30 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00677053

Show 103 Study Locations

Sponsors and Collaborators

Takeda

Investigators

Study Director:

Executive Medical Director Clinical Science

Takeda

More Information

No publications provided

Responsible Party:	Takeda
ClinicalTrials.gov Identifier:	NCT00677053 History of Changes
Other Study ID Numbers:	TAK-442_202, U1111-1112-5867
Study First Received:	May 9, 2008
Last Updated:	February 1, 2012
Health Authority:	United States: Food and Drug Administration Canada: Health Canada Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica Chile: Instituto de Salud Publica de Chile Peru: Ministry of Health Brazil: National Committee of Ethics in Research Romania: National Medicines Agency Serbia and Montenegro: Agency for Drugs and Medicinal Devices Russia: Ministry of Health of the Russian Federation Belgium: Federal Agency for Medicinal Products and Health Products Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) Bulgaria: Bulgarian Drug Agency Hungary: National Institute of Pharmacy South Africa: Medicines Control Council India: Ministry of Health United Kingdom: Medicines and Healthcare Products Regulatory Agency Germany: Federal Institute for Drugs and Medical Devices South Korea: Korea Food and Drug Administration (KFDA) Estonia: The State Agency of Medicine

Keywords provided by Takeda:

Unstable Angina
Myocardial Infarction
Thrombolysis
Anticoagulant
Acute Coronary Syndrome

Additional relevant MeSH terms:

Acute Coronary Syndrome
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Angina Pectoris

Vascular Diseases
Chest Pain
Pain
Signs and Symptoms

ClinicalTrials.gov processed this record on June 17, 2013