Efficacy and safety profile of fenofibrate-coated microgranules 130 mg, with and without food, in patients with hypertriglyceridemia and the metabolic syndrome: an 8-week, randomized, double-blind, placebo-controlled study.

BACKGROUND: The limited bioavailability of certain fenofibrate formulations necessitates administration with food, raising concerns about efficacy and compliance. There is a need for new formulations that have improved bioavailability and eliminate the requirement for administration with food.

OBJECTIVE: The aim of this study was to assess the food-related efficacy of a new formulation of micronized fenofibrate coated on inert microgranules (FF-muG) for the treatment of hypertriglyceridemia in patients exhibiting the metabolic syndrome.

METHODS: This was a randomized, double-blind, placebo-controlled, double-dummy, parallel-group study in patients who had fasting triglyceride (TG) concentrations > or =300 mg/dL and <1000 mg/dL and met National Cholesterol Education Program Adult Treatment Panel III criteria for the metabolic syndrome. A 6-week washout and diet lead-in period was followed by an 8-week treatment period. Eligible patients were randomized to receive either FF-muG 130 mg with food, FF-muG 130 mg without food, or placebo every day for 8 weeks. The primary end point was the mean percent change in TG levels from baseline to the end of treatment; changes in other lipid end points were also assessed. Safety profiles were assessed based on adverse-event reports, changes in clinical laboratory values and vital signs (including electrocardiography), and the findings of physical examinations.

RESULTS: One hundred forty-six patients took part in the study: 54 received FF-muG 130 mg with food, 42 received FF-muG 130 mg without food, and 50 received placebo. The groups were similar in terms of mean age (56 years), sex (59.5%-63.0% men; 37.0%-40.5% women), race (83.3%-100% white), mean body weight (92 kg), mean height (172 cm), mean fasting baseline TG concentrations (480 mg/dL), and other components of the metabolic syndrome. The 2 FF-muG groups (with and without food) showed similar improvements in the dyslipidemia associated with the metabolic syndrome: TG levels decreased a mean of 36.7% and 36.6%, respectively (P < 0.001 vs placebo). The overall frequency of adverse events was similar in the 2 FF-muG groups and did not differ significantly from placebo (63.0%, 61.9%, and 52.0%, respectively). Gastrointestinal disturbances (eg, diarrhea, dyspepsia) occurred more frequently in the 2 FF-muG groups compared with the placebo group (31.5%, 26.2%, and 12.0%; P = NS). Significant increases from baseline in alanine aminotransferase were seen in both FF-muG groups (mean [SEM], 3.77 [2.60] and 11.69 [7.42] U/L, respectively; P < or = 0.05 vs placebo); however, these increases were considered clinically significant in only 5 cases, none of them requiring discontinuation of study drug.

CONCLUSIONS: This study found no inequivalence in the TG-lowering effects of the 2 fenofibrate regimens compared with placebo. Both regimens were well tolerated. Thus, FF-muG 130 mg administered without regard to meals appears to be efficacious and well tolerated for the treatment of hypertriglyceridemia in patients exhibiting the metabolic syndrome.