Efficacy and safety of ABT-335 (fenofibric acid) in combination with rosuvastatin in patients with mixed dyslipidemia: a phase 3 study

Atherosclerosis. 2009 May;204(1):208-15. doi: 10.1016/j.atherosclerosis.2008.09.027. Epub 2008 Oct 5.

Abstract

Objective: To evaluate a new formulation of fenofibric acid (ABT-335) co-administered with 2 doses of rosuvastatin in patients with mixed dyslipidemia.

Methods: In a phase 3, multicenter, randomized, double-blind, active-controlled study, a total of 1445 patients with LDL-C>or=130 mg/dL, TG>or=150 mg/dL, and HDL-C<40 mg/dL (<50 mg/dL for women) were randomized to either ABT-335 (135 mg), rosuvastatin (10, 20, or 40 mg), or ABT-335+rosuvastatin 10 or 20 mg, and treated for 12 weeks. The primary efficacy comparisons were mean percent change in HDL-C and TG (ABT-335+rosuvastatin vs. corresponding dose of rosuvastatin), and LDL-C (ABT-335+rosuvastatin vs. ABT-335).

Results: Combination therapy with ABT-335+rosuvastatin 10 mg resulted in significantly (p<0.001) greater improvements in HDL-C (20.3% vs. 8.5%) and TG (-47.1% vs. -24.4%) compared to rosuvastatin 10 mg; and LDL-C (-37.2% vs. -6.5%) compared to ABT-335. Similarly, significantly (p<0.001) greater improvements were observed with ABT-335+rosuvastatin 20 mg in HDL-C (19.0% vs. 10.3%) and TG (-42.9% vs. -25.6%) compared to rosuvastatin 20 mg; and LDL-C (-38.8% vs. -6.5%) compared to ABT-335 monotherapy. Greater improvements in multiple secondary endpoints were noted with combination therapy compared to prespecified monotherapies. Both combination therapy doses were generally well tolerated, with a safety profile consistent with ABT-335 and rosuvastatin monotherapies. No rhabdomyolysis or unexpected hepatic, renal, or muscle safety signals were identified.

Conclusion: In patients with mixed dyslipidemia, combination therapy with ABT-335+rosuvastatin resulted in more effective control of multiple lipid parameters than either monotherapy alone, with a safety profile similar to both monotherapies. This combination may be an appropriate therapeutic option to treat mixed dyslipidemia.

Trial registration: ClinicalTrials.gov NCT00300482.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anticholesteremic Agents / adverse effects
  • Anticholesteremic Agents / therapeutic use*
  • Biomarkers / blood
  • Canada
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Double-Blind Method
  • Drug Therapy, Combination
  • Dyslipidemias / blood
  • Dyslipidemias / drug therapy*
  • Female
  • Fenofibrate / adverse effects
  • Fenofibrate / analogs & derivatives*
  • Fenofibrate / therapeutic use
  • Fluorobenzenes / adverse effects
  • Fluorobenzenes / therapeutic use*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Male
  • Middle Aged
  • Puerto Rico
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use*
  • Rosuvastatin Calcium
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use*
  • Treatment Outcome
  • Triglycerides / blood
  • United States

Substances

  • Anticholesteremic Agents
  • Biomarkers
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Fluorobenzenes
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrimidines
  • Sulfonamides
  • Triglycerides
  • Rosuvastatin Calcium
  • fenofibric acid
  • Fenofibrate

Associated data

  • ClinicalTrials.gov/NCT00300482