Clinical Drug Investigation

, Volume 28, Issue 10, pp 625–634 | Cite as

Evaluation of a New Formulation of Fenofibric Acid, ABT-335,Co-Administered with Statins

Study Design and Rationale of a Phase III Clinical Programme
  • Peter H. Jones
  • Harold E. Bays
  • Michael H. Davidson
  • Maureen T. Kelly
  • Susan M. Buttler
  • Carolyn M. Setze
  • Darryl J. Sleep
  • James C. Stolzenbach
Original Research Article

Abstract

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.

Methods:

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.

Conclusion:

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.

Notes

Acknowledgements

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.

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Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  • Peter H. Jones
    • 1
  • Harold E. Bays
    • 2
  • Michael H. Davidson
    • 3
  • Maureen T. Kelly
    • 4
  • Susan M. Buttler
    • 4
  • Carolyn M. Setze
    • 4
  • Darryl J. Sleep
    • 4
  • James C. Stolzenbach
    • 4
  1. 1.Baylor College of MedicineHoustonUSA
  2. 2.Louisville Metabolic and Atherosclerosis Research CenterLouisvilleKentuckyUSA
  3. 3.Pritzker School of MedicineUniversity of ChicagoChicagoUSA
  4. 4.AbbottAbbott ParkUSA

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