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A clinical trial to study the safety and efficacy of the study drug when added to atorvastatin plus standard of care in subjects with Acute Coronary syndromes (ACS).

Phase 3
Conditions
Health Condition 1: null- Acute Coronary Syndromes
Registration Number
CTRI/2011/05/001713
Lead Sponsor
Anthera Pharmaceuticals Inc
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Other (Terminated)
Sex
Not specified
Target Recruitment
6500
Inclusion Criteria

1. Men and women equal and above 40 years of age

2. A diagnosis of unstable angina, non-ST-segment elevation myocardial infarction (NSTEMI), or ST-segment elevation

myocardial infarction (STEMI)

Unstable angina is defined as:

Chest pain symptomatic of ischemia or angina occurring at

rest or on minimal exertion with a pattern of increasing

frequency or severity, lasting 10 minutes and consistent

with myocardial ischemia within 24 hours prior to

hospitalization, new or dynamic ST-segment depression or prominent T-wave inversion changes in at least 2 contiguous leads.

In addition subjects meeting the above criteria for unstable angina must also have either troponin I, troponin T or CK-MB above the LLD but below the 99th percentile of the upper reference limit (URL) and not due to cardioversion or underlying cardiovascular (CHF, cardiomyopathy) or renal disease.

NSTEMI is defined as:

Chest pain symptomatic of ischemia, No electrocardiogram (ECG) changes, or ST-depression, or T wave changes (i.e., no new Q waves on serial ECGs) and increase in cardiac troponin local limit for the definition of myocardial infarction or increase in CK-MB isoenzyme URL

STEMI is defined as:

Chest pain symptomatic of ischemia, ST segment elevation and associated T wave changes or ST-segment elevation of at least 2 mm in 2 contiguous leads, either of which persisting for longer than 15 minutes and increase in cardiac troponin local limit for the definition of myocardial infarction or increase in CK-MB URL

3. All subjects (unstable angina, NSTEMI, or STEMI) must have the presence of at least one of the following risk factors:

i. Diabetes Mellitus or

ii. Presence of any 3 of the following characteristics of

metabolic syndrome

- Waist circumference 102 cm in males, 88 cm in females

- Serum triglycerides greater than or equal to 150 mg/dL (greater than or equal to 1.7 mmol/L)

- HDL-C 40 mg/dL (1 mmol/L) in males, 50 mg/dL (1.3 mmol/L) in females

- Blood pressure greater than or equal to 130/85 mmHg

- Plasma glucose greater than or equal to 110 mg/dL (greater than or equal to 6.1 mmol/L) or

iii. history of cerebrovascular disease (stroke or TIA) or

iv. history of peripheral vascular disease or

v. previous CABG or

vi. previous documented myocardial infarction or

vii. previous coronary revascularization

5. Subjects must be randomized within less than or equal to 96 hours of hospital admission for the index event, or if already hospitalized, within less than or equal to 96 hours of index event diagnosis

6. Revascularization, if required or planned, must occur prior to

randomization

Exclusion Criteria

1. Subjects enrolled in another experimental (interventional) protocol within the past 30 days prior to Screening.

2. Subjects treated for cancer within the previous 5 years except for skin basal cell carcinoma or carcinoma in situ of the cervix, with measures other than a minor, complete surgical excision or radiation therapy (e.g. chemotherapy)

3. The presence of any severe liver disease with cirrhosis, active hepatitis, active chronic hepatitis, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 3 x ULN, biliary obstruction with hyperbilirubinemia (total bilirubin 2 x ULN)

4. Active cholecystitis, gall bladder symptoms, or any hepatobiliary

abnormalities

5. The presence of severe renal impairment (creatinine clearance [CrCl] 30 mL/min or creatinine 3 x ULN), nephrotic syndrome, or subjects undergoing dialysis

6. Uncontrolled diabetes mellitus (known hemoglobin A1c

[HbA1c] 11% within the last 1 month prior to Screening)

7. Females who are nursing, pregnant, or intend to become pregnant during the time of the study, or females of childbearing potential who have a positive pregnancy test during screening evaluation. Women of child-bearing potential must also use a reliable method of birth control during the study and for 1 month following completion of therapy. A reliable method for this study is defined as one of the following: oral or injectable contraceptives, intrauterine device (IUD), contraceptive implants, tubal ligation,

hysterectomy, a double barrier method (diaphragm with spermicidal foam or jelly, or a condom).

8. Subjects who have a history of alcohol or drug abuse within 1 year of study entry

9. Subjects living too far from participating center or unable to

return for follow-up visits

10. Subjects who in the opinion of the Investigator are a poor

medical or psychiatric risk for therapy with an investigational drug, are unreliable, or have an incomplete understanding of the study which may affect their ability to take drugs as prescribed or comply with instructions

11. Known human immunodeficiency virus (HIV), Hepatitis B virus (HBV), Hepatitis C virus (HCV), or tuberculosis infection

12. Acute bacterial, fungal or viral infection

13. Subjects currently taking drugs that are potent inhibitors of cytochrome P450 unless they can be withdrawn

14. Subjects with New York Heart Association (NYHA) Class III or IV heart failure, or if known, left ventricular ejection fraction (LVEF) 30%

15. Subjects with moderate or severe aortic stenosis, aortic regurgitation, mitral stenosis or mitral regurgitation

16. Ventricular arrhythmias requiring chronic drug treatment or

implantable cardioverter-defibrillator (ICD)

17. Subjects with no stenosis or stenosis 50% on angiography, if known

18. Subjects with a pacemaker or persistent left bundle branch block (LBBB)

19. Fasting triglyceride levels of more than or equal to 400mg/dL (4.5 mmol/L)

20. Subjects who have a history of statin intolerance or a significant myopathy or rhabdomyolysis with any lipidaltering drugs

21. Subjects currently treated with the maximum labeled dose of a statin and not at LDL-C target for their level of risk as defined by NCEP ATP

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
To determine whether 16 weeks of<br>treatment with A-002 plus atorvastatin and standard of care is superior to placebo plus atorvastatin and standard of care for reducing the hazard of the first occurrence of the combined endpoint of cardiovascular death, non fatal myocardial infarction, non-fatal stroke, or documented unstable angina with objective evidence of ischemia requiring hospitalization.Timepoint: 16 Weeks
Secondary Outcome Measures
NameTimeMethod
To determine whether A-002 plus atorvastatin and standard of care is superior to placebo plus atorvastatin and standard of care for reducing the occurrence of the hazard of the combined endpoint of all-cause mortality, non-fatal myocardial infarction, non-fatal stroke, or documented unstable angina with objective evidence of ischemia requiring hospitalization, or multiple occurrences of the non-fatal components of the composite primary endpoint.Timepoint: 16 Weeks
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