PLASMA 2 Trial: Examination of Once Daily (QD) Dosing of A-002 In Subjects With Stable Coronary Artery Disease (PLASMA 2)
Primary Purpose
Coronary Artery Disease
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
A-002
Sponsored by
About this trial
This is an interventional prevention trial for Coronary Artery Disease focused on measuring Coronary, Artery, Artheroschlerosis, Phospholipase, CAD, Coronary Artery Disease (CAD)
Eligibility Criteria
Inclusion Criteria:
Subjects are eligible for inclusion if they meet the following inclusion criteria:
- Men and women ≥18 years of age
- Written informed consent from the subject
- Stable CAD
- Stable medical condition, will be compliant and able to comply with the requirements of the protocol
Exclusion Criteria:
Subjects must NOT meet any of the following exclusion criteria:
- Planned coronary artery bypass surgery (CABG)
- Acute or chronic heart failure as defined by the New York Heart Association (NYHA) classification as functional Class III or Class IV
- Hospitalization for acute coronary syndrome (ACS) if troponin >0.1 ng/mL in the preceding 6 weeks
- Hospitalization for ST-segment elevation acute myocardial infarction (STEMI) in the preceding 12 weeks
- Subjects with chronic inflammatory disease (e.g., rheumatoid arthritis), inflammatory bowel disease, recent (12 weeks) systemic or localized infection (the latter requiring clinical intervention), or major surgery
- hs-CRP ≥15 mg/L repeated on at least 2 occasions >24 hours apart due to non-cardiovascular systemic inflammatory conditions (e.g., rheumatoid disease)
- Subjects enrolled in another experimental (interventional) protocol within the past 30 days prior to Screening or prior experience with A-002.
- 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 (e.g., chemotherapy), or radiation therapy
- Subjects who have received immunosuppressant therapy within 30 days prior to entry
- Subjects who have received anti-tumor necrosis factor (for example, infliximab) therapy within 6 months prior to entry
- The presence of severe liver disease with cirrhosis, recent active hepatitis, active chronic hepatitis, ALT or AST >3 x upper limit of normal, biliary obstruction with hyperbilirubinemia (total bilirubin >2 x upper limit of normal)
- Active cholecystitis, gall bladder symptoms, or potential hepato-biliary abnormalities
- The presence of moderate or severe renal impairment (CrCl <60 mL/min or creatinine >1.5 x upper limit of normal), nephrotic syndrome, or subjects undergoing dialysis
- Uncontrolled diabetes mellitus (known HbA1c >11% within the last 1 month prior to screening)
- Females who are nursing, pregnant, or intend to become pregnant during the time of the study, or subjects who have a positive serum pregnancy test at Visit 1 (if the subject is a female of child-bearing potential). 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).
- Subjects who have a history of alcohol or drug abuse within 1 year of study entry
- Subject living too far from participating center or unable to return for follow-up visits
- 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
- Known human immunodeficiency virus (HIV), Hepatitis B virus (HBV), or Hepatitis C Virus (HCV) infection
- Treatment with any systemic corticosteroid within the 30-day period prior to study entry or the use of inhaled steroids within the 14-day period prior to study entry
Sites / Locations
- Mobile Heart Specialists
- Sonoran Health Specialists
- Pasco Cardiology Center
- Charlotte Cardiovascular Institute
- Florida Cardiovascular Research Institute
- Augusta Cardiology Clinic
- Louisville Cardiology Medical Group
- Maine Research Associates
- United Medical Associates
- Cardiology PC
- Austin Heart
- Clinical Research Associates of Tidewater
- Wisconsin Heart, SC
Outcomes
Primary Outcome Measures
The primary objective of this study is to determine the effect of once daily (QD) dosing of A-002 on sPLA2 levels and activity
Secondary Outcome Measures
Determine the effect of QD dosing of A-002 on sPLA2 levels and activity at each time point (Weeks 2, 4, and 8)
Compare the effect of QD dosing of A-002 on sPLA2 enzyme levels and markers of inflammation
Determine plasma drug concentrations with QD dosing
Full Information
NCT ID
NCT00525954
First Posted
September 4, 2007
Last Updated
January 3, 2008
Sponsor
Anthera Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT00525954
Brief Title
PLASMA 2 Trial: Examination of Once Daily (QD) Dosing of A-002 In Subjects With Stable Coronary Artery Disease
Acronym
PLASMA 2
Official Title
Phospholipase Levels And Serological Markers of Atherosclerosis 2: An Examination of Once Daily (QD) Dosing of A-002 In Subjects With Stable Coronary Artery Disease
Study Type
Interventional
2. Study Status
Record Verification Date
January 2008
Overall Recruitment Status
Completed
Study Start Date
September 2007 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
December 2007 (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
Anthera Pharmaceuticals
4. Oversight
5. Study Description
Brief Summary
The study will be conducted at up to 25 U.S. centers and will be a double-blind randomized parallel group placebo controlled study among subjects with stable coronary artery disease (CAD). Subjects will be randomized to receive either placebo tablets or one of 2 orally active doses of A-002. The duration of study drug therapy will be 8 weeks.
Detailed Description
A-002 represents a novel therapy for the treatment of atherosclerosis and coronary artery disease (CAD). Through the inhibition of activity A-002 may provide multifunctional activity directed against key facets of the disease process, namely a) inflammation, b) atherogenic lipid profiles and c) the atherosclerotic process. Non-clinical and clinical data from recent studies have demonstrated the benefit of early and aggressive anti-inflammatory therapy to reduce cardiovascular risk. Recent clinical studies have provided a strong association between levels and cardiovascular event risk. The proposed Phase 2 clinical pharmacology study (Study No. AN-CVD-2222) will examine the effects of 2 different doses of A-002 compared with placebo, on enzyme levels and activity after 8 weeks of treatment. In addition, the effect of treatment on inflammatory markers of cardiovascular risk (C-reactive protein [CRP]), lipid levels and lipoprotein subclasses and other soluble biomarkers (e.g., ICAM-1, VCAM-1, TNF, MCP-1 etc) will also be assessed.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Disease
Keywords
Coronary, Artery, Artheroschlerosis, Phospholipase, CAD, Coronary Artery Disease (CAD)
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
A-002
Primary Outcome Measure Information:
Title
The primary objective of this study is to determine the effect of once daily (QD) dosing of A-002 on sPLA2 levels and activity
Secondary Outcome Measure Information:
Title
Determine the effect of QD dosing of A-002 on sPLA2 levels and activity at each time point (Weeks 2, 4, and 8)
Title
Compare the effect of QD dosing of A-002 on sPLA2 enzyme levels and markers of inflammation
Title
Determine plasma drug concentrations with QD dosing
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects are eligible for inclusion if they meet the following inclusion criteria:
Men and women ≥18 years of age
Written informed consent from the subject
Stable CAD
Stable medical condition, will be compliant and able to comply with the requirements of the protocol
Exclusion Criteria:
Subjects must NOT meet any of the following exclusion criteria:
Planned coronary artery bypass surgery (CABG)
Acute or chronic heart failure as defined by the New York Heart Association (NYHA) classification as functional Class III or Class IV
Hospitalization for acute coronary syndrome (ACS) if troponin >0.1 ng/mL in the preceding 6 weeks
Hospitalization for ST-segment elevation acute myocardial infarction (STEMI) in the preceding 12 weeks
Subjects with chronic inflammatory disease (e.g., rheumatoid arthritis), inflammatory bowel disease, recent (12 weeks) systemic or localized infection (the latter requiring clinical intervention), or major surgery
hs-CRP ≥15 mg/L repeated on at least 2 occasions >24 hours apart due to non-cardiovascular systemic inflammatory conditions (e.g., rheumatoid disease)
Subjects enrolled in another experimental (interventional) protocol within the past 30 days prior to Screening or prior experience with A-002.
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 (e.g., chemotherapy), or radiation therapy
Subjects who have received immunosuppressant therapy within 30 days prior to entry
Subjects who have received anti-tumor necrosis factor (for example, infliximab) therapy within 6 months prior to entry
The presence of severe liver disease with cirrhosis, recent active hepatitis, active chronic hepatitis, ALT or AST >3 x upper limit of normal, biliary obstruction with hyperbilirubinemia (total bilirubin >2 x upper limit of normal)
Active cholecystitis, gall bladder symptoms, or potential hepato-biliary abnormalities
The presence of moderate or severe renal impairment (CrCl <60 mL/min or creatinine >1.5 x upper limit of normal), nephrotic syndrome, or subjects undergoing dialysis
Uncontrolled diabetes mellitus (known HbA1c >11% within the last 1 month prior to screening)
Females who are nursing, pregnant, or intend to become pregnant during the time of the study, or subjects who have a positive serum pregnancy test at Visit 1 (if the subject is a female of child-bearing potential). 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).
Subjects who have a history of alcohol or drug abuse within 1 year of study entry
Subject living too far from participating center or unable to return for follow-up visits
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
Known human immunodeficiency virus (HIV), Hepatitis B virus (HBV), or Hepatitis C Virus (HCV) infection
Treatment with any systemic corticosteroid within the 30-day period prior to study entry or the use of inhaled steroids within the 14-day period prior to study entry
Facility Information:
Facility Name
Mobile Heart Specialists
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36608
Country
United States
Facility Name
Sonoran Health Specialists
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85260
Country
United States
Facility Name
Pasco Cardiology Center
City
Hudson
State/Province
Florida
ZIP/Postal Code
34667
Country
United States
Facility Name
Charlotte Cardiovascular Institute
City
Port Charlotte
State/Province
Florida
ZIP/Postal Code
33952
Country
United States
Facility Name
Florida Cardiovascular Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33609
Country
United States
Facility Name
Augusta Cardiology Clinic
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30901
Country
United States
Facility Name
Louisville Cardiology Medical Group
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40207
Country
United States
Facility Name
Maine Research Associates
City
Auburn
State/Province
Maine
ZIP/Postal Code
04210
Country
United States
Facility Name
United Medical Associates
City
Binghamton
State/Province
New York
ZIP/Postal Code
13901
Country
United States
Facility Name
Cardiology PC
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Austin Heart
City
Austin
State/Province
Texas
ZIP/Postal Code
78705
Country
United States
Facility Name
Clinical Research Associates of Tidewater
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
Facility Name
Wisconsin Heart, SC
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53715
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
21081550
Citation
Rosenson RS, Elliott M, Stasiv Y, Hislop C; PLASMA II Investigators. Randomized trial of an inhibitor of secretory phospholipase A2 on atherogenic lipoprotein subclasses in statin-treated patients with coronary heart disease. Eur Heart J. 2011 Apr;32(8):999-1005. doi: 10.1093/eurheartj/ehq374. Epub 2010 Nov 16.
Results Reference
derived
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PLASMA 2 Trial: Examination of Once Daily (QD) Dosing of A-002 In Subjects With Stable Coronary Artery Disease
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