Approved December 2008
dyslipidemia, hypertriglyceridemia and hyperlipidemia
Trilipix (fenofibric acid) is a lipid regulating agent available as delayed release capsules for oral administration. Fenofibric acid activates the peroxisome proliferator activated receptor a (PPARa). PPARs affect the expression of target genes involved in cell proliferation, cell differentiation and in immune and inflammation responses.
Trilipix as an adjunct to diet is specifically indicated for:
1) Co-administration Therapy with Statins for the Treatment of Mixed Dyslipidemia
To reduce TG and increase HDLC in patients with mixed dyslipidemia and CHD or a CHD risk equivalent who are on optimal statin therapy to achieve their LDL-C goal.
2) Treatment of Severe Hypertriglyceridemia
To reduce TG.
3) Treatment of Primary Hyperlipidemia or Mixed Dyslipidemia
To reduce elevated LDL-C, Total-C, TG, and Apo B, and to increase HDL-C.
Trilipix is supplied as a tablet designed for oral administration.
The recommended intial dose of the drug for co-administration therapy with statins for the treatment of mixed dyslipidemia is 135 mg daily. Co-administration with the maximum dose of a statin should be avoided.
The recommended initial dose of the drug for severe hypertriglyceridemia is 45 to 135 mg once daily.
The recommended initial dose of the drug for primary hyperlipidemia or mixed dyslipidemia is 135 mg once daily.
FDA approval of Trilipix in combination with statins was based on four phase III studies: three 12-week, double-blind, placebo controlled studies and one 52-week, long-term, open-label extension study. A total of 2,698 subjects with mixed dyslipidemia were enrolled.
For the three 12-week studies: Study 1 subjects received Trilipix co-administered with 10 mg or 20 mg rosuvastatin; Study 2 subjects received Trilipix co-administered with 20 mg or 40 mg simvastatin; Study 3 subjects received Trilipix co-administered with 20 mg or 40 mg atorvastatin. The primary efficacy endpoints for all three studies were mean percent changes from baseline to final value in HDL-C, TG, and LDL-C. For each statin dose co-administered with Trilipix, there were three primary comparisons. For HDL-C and TG, Trilipix co-administered with each statin dose was compared with statin monotherapy at the corresponding dose. For LDL-C, Trilipix co-administered with each statin dose was compared with Trilipix monotherapy. All three primary comparisons were required to demonstrate superiority of the combination therapy over the corresponding monotherapy. In the pooled analysis, Trilipix co-administered with both low-dose statins and moderate-dose statins resulted in mean percent increases (18.1% and 17.5%) in HDL-C and mean percent decreases (-43.9% and -42.0%) in TG that were significantly greater than the corresponding dose of statin monotherapy (7.4% and 8.7% for HDL-C; -16.8% and -23.7% for TG). In addition, both doses of combination therapy resulted in mean percent decreases (-33.1% and -34.6%) in LDL-C that were significantly greater than Trilipix monotherapy (-5.1%).
The subjects who completed the 12-week treatment period of any of the studies were eligible to participate in the 52-week long-term extension study. A total of 1,895 subjects were enrolled, 568 of whom completed treatment. The subjects received Trilipix co-administered with the moderate-dose of the statin that had been used in the double-blind, controlled study in which they were enrolled. Mean 52-week values and mean percent change from baseline were 91.7 mg/dL (-38.2%) for LDL-C, 47.3 mg/dL (+24.0%) for HDL-C, 135.5 mg/dL (-47.6%) for TG, 117.9 mg/dL (-45.7%) for non-HDL-C, 26.2 mg/dL (-53.1%) for VLDLC, 165.2 mg/dL (-35.4%) for Total-C, and 81.4 mg/dL (-43.6%) for Apo B.
FDA approval of Trilipix for the treatment of hypertriglyceridemia was based on the results of two clinical trials. These randomized, double-blind, placebo-controlled studies enrolled 147 subjects. The two protocols were similar except that one trial enrolled subjects with baseline TG levels of 500 to 1500 mg/dL, and the other trial enrolled subjects with baseline TG levels of 350 to 500 mg/dL. Treatment with fenofibrate at dosages equivalent to 135 mg once daily of Trilipix decreased primarily VLDL-TG and VLDL-C. Treatment of patients with elevated TG often results in an increase of LDL-C.
FDA approval of Trilipix for the treatment of primary hypercholesterolemia (Heterozygous Familial and Nonfamilial) and mixed dyslipidemia was based on the results of four clinical studies. These randomized, placebo-controlled, double-blind, parallel-group studies enrolled 646 subjects who received Trilipix 135 mg once daily. Fenofibrate therapy lowered LDL-C, Total-C, and the LDL-C/HDL-C ratio. Fenofibrate therapy also lowered triglycerides and raised HDL-C. In a subset of the subjects, measurements of Apo B were conducted. Fenofibrate treatment significantly reduced Apo B from baseline to endpoint as compared with placebo (-25.1% vs. 2.4%, p < 0.0001).
Trilipix (fenofibric acid) is a lipid regulating agent available as delayed release capsules for oral administration. Fenofibric acid activates the peroxisome proliferator activated receptor a (PPARa). Through this mechanism, fenofibric acid increases lipolysis and elimination of triglyceride-rich particles from plasma by activating lipoprotein lipase and reducing production of Apo CIII (an inhibitor of lipoprotein lipase activity). The resulting decrease in triglycerides produces an alteration in the size and composition of LDL from small, dense particles to large buoyant particles, which have a greater affinity for cholesterol receptors and are catabolized rapidly. PPARa activation also induces an increase in the synthesis of HDL-C and Apo AI and AII.
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