Evaluation of a New Formulation of Fenofibric Acid, ABT-335,Co-Administered with Statins
- 77 Downloads
Background and objective:
Atherogenic lipid parameters in patients with mixed dyslipidaemia have been demonstrated to increase atherosclerotic coronary heart disease (CHD) risk. Clinical studies have shown that HMG-CoA reductase inhibitor (statin) and fibric acid derivative (fibrate) combination therapy is effective at improving multiple lipid abnormalities in different patient populations at increased risk of CHD. However, inconsistencies with respect to trial designs and safety issues have limited the clinical use of this combination therapy. A comprehensive, controlled clinical trial programme was thus designed to evaluate three separate statins in combination with ABT-335, a new formulation of fenofibric acid.
Three separate 22-week, phase III, double-blind, active-controlled trials will evaluate combination therapy with ABT-335 135 mg/day and either rosuvastatin (10 mg/day and 20 mg/day), atorvastatin (20 mg/day and 40 mg/day) or simvastatin (20 mg/day and 40 mg/day) in comparison to either ABT-335 or the corresponding statin monotherapy. An approximate total of 2400 patients with elevated triglycerides (TG) [≥150 mg/dL], reduced high-density lipoprotein cholesterol (HDL-C) [<40 mg/dL for men and <50 mg/dL for women], and elevated low-density lipoprotein cholesterol (LDL-C) [≥130 mg/dL] will be randomized to one of six intervention arms per trial (two combination therapy and four monotherapy groups). The pre-specified primary efficacy endpoint is a composite of the mean percent changes in HDL-C and TG (comparing each combination therapy with the corresponding statin monotherapy dose) and LDL-C (comparing each combination therapy with ABT-335 monotherapy). Secondary endpoints include mean percent changes in non-HDL-C, very LDL-C, total cholesterol, apolipoprotein B and high sensitivity C-reactive protein levels. At study end, patients may enrol in a 12-month open-label extension study that will evaluate the longterm efficacy and safety of combination therapy.
This is the largest phase III randomized, controlled clinical programme to date evaluating the efficacy and safety of the combined use of a new formulation of fenofibric acid (ABT-335) with three commonly prescribed statins in patients with mixed dyslipidaemia.
Abbott provided financial support for the study design, collection of data, and manuscript writing. Dr Peter Jones has served as a consultant and a member of advisory panels and/or speakers’ bureaus for Abbott, AstraZeneca and Merck. He has also received research support from Abbott and AstraZeneca. Dr Harold Bays has received research grants from and served as a consultant, speaker and/or advisor to Abbott, AstraZeneca, Merck, Merck/Schering Plough and Pfizer. Dr Michael Davidson has received research support and an honorarium and served as a consultant/on speakers’ bureaus for Abbott, AstraZeneca, Merck and Pfizer. Dr Maureen Kelly, Susan Buttler, Carolyn Setze, Dr Darryl Sleep and Dr James Stolzenbach are employed by Abbott. Dr Erin Blondell provided assistance in manuscript writing and preparation.
- 10.Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002 Dec 17; 106(25): 3143–421Google Scholar
- 11.American Diabetes Association. Standards of medical care in diabetes: 2007. Diabetes Care 2007 Jan; 30 Suppl. 1: S4-S41Google Scholar
- 12.Graham I, Atar D, Borch-Johnsen K, et al. European guidelines on cardiovascular disease prevention in clinical practice: full text. Fourth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts). Eur J Cardiovasc Prev Rehabil 2007 Sep; 14Suppl. 2: S1–113PubMedCrossRefGoogle Scholar
- 13.Executive summary of the third report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001 May 16; 285 (19): 2486-97Google Scholar
- 22.JBS 2: Joint British Societies’ guidelines on prevention of cardiovascular disease in clinical practice. Heart 2005 Dec; 91Suppl. 5: v1–52Google Scholar
- 23.Keevil JG, Cullen MW, Gangnon R, et al. Implications of cardiac risk and low-density lipoprotein cholesterol distributions in the United States for the diagnosis and treatment of dyslipidemia: data from National Health and Nutrition Examination Survey 1999 to 2002. Circulation 2007 Mar 20; 115(11): 1363–70PubMedCrossRefGoogle Scholar
- 38.Fazio S, Linton MF. The role of fibrates in managing hyperlipidemia: mechanisms of action and clinical efficacy. Curr Atheroscler Rep} 2004; 6 148-57Google Scholar
- 39.Zocor (simvastatin) product package insert. West Point (PA): Merck & Co., Inc., Jun 2008Google Scholar
- 40.Lipitor (atorvastatin calcium) product package insert. New York (NY): Pfizer Inc., Nov 2007Google Scholar
- 41.Crestor (rosuvastatin calcium) product package insert. Wilmington (DE): AstraZeneca Pharmaceuticals LP, Nov 2007Google Scholar
- 42.TriCor (fenofibrate tablets) product package insert. Abbott Park (IL): Abbott, Oct 2007Google Scholar
- 43.American Heart Association. An eating plan for healthy Americans: our American Heart Association diet. AHA publication no. 50-1481AGoogle Scholar
- 44.Rifai N, Warnick GR, Dominiczak MH, editors. Handbook of lipoprotein testing. 2nd ed. Washington, DC: AACC Press, 2000Google Scholar