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).
Scientific Title of Study
Evaluation of the Safety and Efficacy of Short-term A-002 Treatment in Subjects with Acute Coronary Syndromes.
Secondary IDs if Any
Secondary ID
Identifier
AN-CVD2233
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study) Modification(s)
Name
Dr Bankim Chauhan
Designation
Senior Project Manager
Affiliation
Trident Clinical Research India Pvt. Ltd.
Address
Trident Clinical Research India Pvt. Ltd. Office No. 4, 3rd Floor, BIZ Park, Road No 16U, Wagle Estate, MIDC, Thane (West) Thane MAHARASHTRA 400604 India
Phone
022-25800414
Fax
02225800417
Email
bchauhan@tridentclinicalresearch.com
Details of Contact Person Scientific Query
Name
DrBankim Chauhan
Designation
Senior Project Manager
Affiliation
Trident Clinical Research India Pvt. Ltd.
Address
Trident Clinical Research India Pvt. Ltd. Office No. 4, 3rd Floor, BIZ Park, Road No 16U, Wagle Estate, MIDC, Thane (West) Thane MAHARASHTRA 400604 India
Phone
022-25800414
Fax
02225800417
Email
bchauhan@tridentclinicalresearch.com
Details of Contact Person Public Query
Name
Dr Samir Sadekar
Designation
Managing Director
Affiliation
Trident Clinical Research India Pvt. Ltd.
Address
Trident Clinical Research India Pvt. Ltd. Office No. 4, 3rd Floor, BIZ Park, Road No 16U, Wagle Estate, MIDC, Thane (West) Thane MAHARASHTRA 400604 India
Phone
022-25800414
Fax
022-25800417
Email
ssadekar@tridentclinicalresearch.com
Source of Monetary or Material Support
Anthera Pharmaceuticals, Inc.
25801 Industrial Boulevard, Suite B
Hayward, CA 94545
U.S.A.
Primary Sponsor
Name
Anthera Pharmaceuticals Inc
Address
25801 Industrial Boulevard, Suite BHayward, CA 94545U.S.A.
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
Trident Clinical Research India Pvt Ltd
Office No. 4, 3rd Floor, BIZ Park, Road No 16U, Wagle Estate, MIDC, Thane (W)- 400604. Maharashtra. India
Countries of Recruitment
Australia Canada Czech Republic Georgia Germany Hungary India Italy Lebanon Netherlands New Zealand Poland Russian Federation Spain Ukraine United States of America
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
ExclusionCriteria
Details
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
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Outcome Assessor Blinded
Primary Outcome
Outcome
TimePoints
To determine whether 16 weeks of
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.
16 Weeks
Secondary Outcome
Outcome
TimePoints
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.
16 Weeks
Target Sample Size
Total Sample Size="6500" Sample Size from India="650"
This is a double-blind, randomized, parallel group, placebo controlled study in subjects presenting with an ACS. Up to 6500 subjects will be randomized to receive either A-002 500 mg once daily (QD) or placebo tablets in addition to atorvastatin QD and standard of care. Treatment will be 16 weeks in duration. The dose of atorvastatin shall be adjusted after 8 weeks if LDL-C of subject is more than or equal to 100 mg/dL, but otherwise must remain stable throughout the16-week duration of study. The survival status for all enrolled subjects will be ascertained 6 months after they complete the study. Randomization must occur within less than or equal to 96 hours of hospitalization for the index ACS event, or if already hospitalized, within 96 hours of index event diagnosis. Follow-up visits occur at 1, 2, 4, 6, 24, 48, 72 and 96 and Weeks 1, 2, 4, 8 and 16. Randomization will be stratified by the presence or absence of lipid-altering therapy prior to the index event as well as the type of index event (admission diagnosis of unstable angina, NSTEMI or STEMI). The number of subjects who undergo PCI following the index event and prior to randomization will be limited to no more than 55% of the total study population.