New phase III data showed that in patients with multiple lipid problems, Abbott's investigational TriLipix (ABT-335) combined with AstraZeneca's rosuvastatin (Crestor) led to greater improvements than the pre-specified monotherapy in treating all three key lipids - LDL "bad" cholesterol, HDL "good" cholesterol and triglycerides.
Results from this phase III study were presented at the National Lipid Association's 2008 Scientific Sessions in Seattle.
This phase III trial in more than 1,400 patients is part of the largest clinical program to date designed to evaluate the efficacy and safety of a fibrate in combination with statins. The study combining TriLipix with rosuvastatin met its primary endpoints, with combination therapy significantly improving HDL and triglycerides compared to rosuvastatin monotherapy, and significantly improving LDL compared to TriLipix monotherapy. Both TriLipix combined with rosuvastatin and rosuvastatin monotherapy resulted in clinically meaningful reductions in LDL.
As observed in the trial, combination therapy was generally well tolerated, with reported safety similar to the monotherapies. In this study, no rhabdomyolysis or unexpected liver, kidney or muscle safety signals were identified with monotherapy or when the therapies were combined.
"Patients with mixed dyslipidemia need treatment options that address all three key lipids, including LDL, HDL and triglycerides," said Peter H Jones, MD, FACP, Methodist DeBakey Heart and Vascular Center, Houston, and a lead investigator of the trial. "Results from this study indicate that the combination of TriLipix and Crestor significantly increased HDL, and decreased both LDL and triglycerides. This approach may provide physicians with an important statin/fibrate combination therapeutic option for patients with mixed dyslipidemia".
According to the American Heart Association (AHA), more than 106 million American adults have dyslipidemia. Of the 30 million Americans currently on lipid-altering therapies, the majority are not reaching treatment goals. Treatment guidelines endorsed by the National Cholesterol Education Panel, the American College of Cardiology and the AHA have called for more aggressive management of lipids, including a lower LDL goal for many patients, as well as more aggressive management of HDL and triglycerides.
The efficacy and safety of TriLipix in combination with rosuvastatin was evaluated in a randomized, double-blind, controlled, 12-week, phase III study of 1,445 patients with mixed dyslipidemia. Patients included in the study had multiple lipid problems, with an LDL greater than or equal to 130 mg/dL, triglycerides greater than or equal to 150 mg/dL and HDL less than 40 mg/dL for men and less than 50 mg/dL for women.
Patients were randomized to receive TriLipix (135mg) combined with either 10mg or 20mg of rosuvastatin, TriLipix monotherapy (135mg) or rosuvastatin monotherapy (10mg, 20mg or 40mg). The 40mg rosuvastatin monotherapy arm was included in the study to assess safety and adverse events, but was not included in the statistical analysis.
The primary efficacy comparisons were mean percent change in HDL and triglycerides for the combination versus rosuvastatin alone, and mean percent change in LDL for TriLipix combined with rosuvastatin versus TriLipix alone. The study met all of its primary endpoints. TriLipix in combination with rosuvastatin significantly improved HDL and triglycerides compared to rosuvastatin monotherapy, and significantly improved LDL compared to TriLipix monotherapy.
TriLipix is an investigational new fenofibric acid molecule, currently in clinical development for treating patients with unhealthy lipid levels, including LDL cholesterol, triglycerides and HDL cholesterol. A New Drug Application for TriLipix for use as monotherapy and in combination with statins has been submitted to the US Food and Drug Administration (FDA).