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

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 ≥ 130 mg/dL, TG ≥ 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.