Clinical trial NCT00455546: PLASMA Trial: A Dose-Response Study of A-002 In Subjects With Stable Coronary Artery Disease
Official title: PLASMA Trial: Phospholipase Levels And Serological Markers of Atherosclerosis: A Dose-Response Clinical Pharmacology Study of A-002 In Subjects With Stable Coronary Artery Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Coronary Artery Disease (CAD)
Keywords: Coronary
Artery
Atherosclerosis
Phospholipase
CAD
Lead sponsor: Anthera Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2007-04-03
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The study will be conducted at up to 80 centers worldwide 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 4 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-2221) will examine the effects of 4 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.

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 CABG
* Hospitalization for acute coronary syndrome if troponin level is \>0.1 ng/mL in the preceding 6 weeks
* Hospitalization for ST-segment acute myocardial infarction (STEMI) in the preceding 12 weeks
* Subjects with chronic inflammatory disease (e.g., RA), 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)
* Acute or chronic heart failure as defined by the NYHA classification as functional Class III or Class IV

Primary outcomes:
measure: Comparison of active and placebo treatments with respect to change from Baseline to Week 8 in sPLA2 levels and activity.
Secondary outcomes:
measure: Comparison of active and placebo treatments with respect to change in: Inflammatory markers, lipid and biochemical parameters, and LDL and HDL subclasses.
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Mobile Heart Specialists
state: Alabama
city: Scottsdale
country: United States
facility: Sonoran Health Specialists
state: Arizona
city: Hot Springs
country: United States
facility: Central Arkansas Research
state: Arkansas
city: Ft. Lauderdale
country: United States
facility: Broward General Medical Center
state: Florida
city: Hudson
country: United States
state: Florida
city: Port Charlotte
country: United States
facility: Charlotte Cardiovascuar Research
state: Florida
city: Tampa
country: United States
facility: Florida Cardiovascular Institute
state: Florida
city: Augusta
country: United States
facility: Augusta Cardiology Clinic, PC
state: Georgia
city: Louisville
country: United States
facility: Louisville Cardiology Medical Group
state: Kentucky
city: Auburn
country: United States
facility: Maine Research Associates
state: Maine
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Binghamton
country: United States
facility: United Medical Associates
state: New York
city: Endwell
country: United States
facility: Regional Clinical Research, Inc.
state: New York
city: Syracuse
country: United States
facility: Cardiology, PC
state: New York
city: Oklahoma City
country: United States
facility: Oklahoma Cardiovascular and Hypertension Center
state: Oklahoma
city: Allentown
country: United States
facility: Lehigh Valley Hospital
state: Pennsylvania
city: Camp Hill
country: United States
state: Pennsylvania
city: Rapid City
country: United States
facility: Black Hills Clinical Research Center
state: South Dakota
city: Austin
country: United States
facility: Austin Heart
state: Texas
city: Dallas
country: United States
facility: Cardiopulmonary Research Science and Technology Institute
state: Texas
city: Norfolk
country: United States
facility: Clinical Research Associates of Tidewater
state: Virginia
city: Madison
country: United States
facility: Winsconin Heart, SC
state: Wisconsin
city: Kyiv
country: Ukraine
facility: Strazhesko Institute of Cardiology AMS
state: 03680
city: Dnepropetrovs'k
country: Ukraine
facility: Dnipropetrovs'k State Medical Academy
city: Kharkiv
country: Ukraine
facility: Institute of Therapy of AMS
city: Khirkov
country: Ukraine
facility: Central Clinical Hospital "Ukrzaliznysti"
city: Kviv
country: Ukraine
facility: Strazhesko Institute of Cardiology AMS
city: Kyiv
country: Ukraine
facility: Kiev Central Hospital #1
city: Kyiv
country: Ukraine
facility: City Clinical Hospital No 12
city: Kyiv
country: Ukraine
facility: Scientific Centre of Endocrine Surgery
city: Kyiv
country: Ukraine
facility: Strazhesko Institute of Cardiology AMS
city: Kyiv
country: Ukraine
facility: Institute of Gerontology AMS
city: Kyiv
country: Ukraine
facility: Institute of Gerontology
city: L'viv
country: Ukraine
facility: L'viv Regional State Clinical Treatment and Diagnostics
city: Zaporizhzhya
country: Ukraine
facility: Hospital of "Radioprylad" Plant
Study officials:
References:
citation: Rosenson RS, Hislop C, McConnell D, Elliott M, Stasiv Y, Wang N, Waters DD; PLASMA Investigators. Effects of 1-H-indole-3-glyoxamide (A-002) on concentration of secretory phospholipase A2 (PLASMA study): a phase II double-blind, randomised, placebo-controlled trial. Lancet. 2009 Feb 21;373(9664):649-58. doi: 10.1016/S0140-6736(09)60403-7.