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 bioavallability 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-mu G) 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 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-mu G 130 mg with food, FF-mu G 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-mu G 130 mg with food, 42 received FF-mu G 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-mu G 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-mu G 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-mu G 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-mu G groups (mean [SEM], 3.77 [2.60] and 11.69 [7.42] U/L, respectively; P <= 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-mu G 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. Copyright (c) 2005 Excerpta Medica, Inc.