PLASMA 2 Trial: Examination of Once Daily (QD) Dosing of A-002 In Subjects With Stable Coronary Artery Disease

Coronary Artery Disease Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00525954
• Other study ID #: AN-CVD2222
• Status: Completed
• Phase: Phase 2
• First received: September 4, 2007
• Last updated: January 3, 2008
• Start date: September 2007
• Est. completion date: December 2007

Study information

• Verified date: January 2008
• Source: Anthera Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: December 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Subjects are eligible for inclusion if they meet the following inclusion criteria:

1. Men and women =18 years of age

2. Written informed consent from the subject

3. Stable CAD

4. 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:

1. Planned coronary artery bypass surgery (CABG)

2. Acute or chronic heart failure as defined by the New York Heart Association (NYHA) classification as functional Class III or Class IV

3. Hospitalization for acute coronary syndrome (ACS) if troponin >0.1 ng/mL in the preceding 6 weeks

4. Hospitalization for ST-segment elevation acute myocardial infarction (STEMI) in the preceding 12 weeks

5. 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

6. 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)

7. Subjects enrolled in another experimental (interventional) protocol within the past 30 days prior to Screening or prior experience with A-002.

8. 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

9. Subjects who have received immunosuppressant therapy within 30 days prior to entry

10. Subjects who have received anti-tumor necrosis factor (for example, infliximab) therapy within 6 months prior to entry

11. 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)

12. Active cholecystitis, gall bladder symptoms, or potential hepato-biliary abnormalities

13. 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

14. Uncontrolled diabetes mellitus (known HbA1c >11% within the last 1 month prior to screening)

15. 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).

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

17. Subject living too far from participating center or unable to return for follow-up visits

18. 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

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

20. 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

Study Design

Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• A-002

Locations

Country	Name	City	State
United States	Maine Research Associates	Auburn	Maine
United States	Augusta Cardiology Clinic	Augusta	Georgia
United States	Austin Heart	Austin	Texas
United States	United Medical Associates	Binghamton	New York
United States	Pasco Cardiology Center	Hudson	Florida
United States	Louisville Cardiology Medical Group	Louisville	Kentucky
United States	Wisconsin Heart, SC	Madison	Wisconsin
United States	Mobile Heart Specialists	Mobile	Alabama
United States	Clinical Research Associates of Tidewater	Norfolk	Virginia
United States	Charlotte Cardiovascular Institute	Port Charlotte	Florida
United States	Sonoran Health Specialists	Scottsdale	Arizona
United States	Cardiology PC	Syracuse	New York
United States	Florida Cardiovascular Research Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Anthera Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Determine the effect of QD dosing of A-002 on sPLA2 levels and activity at each time point (Weeks 2, 4, and 8)
Secondary	Compare the effect of QD dosing of A-002 on sPLA2 enzyme levels and markers of inflammation
Secondary	Determine plasma drug concentrations with QD dosing