A once-daily, fixed-dose tablet combining atorvastatin and a novel micronized formulation of fenofibrate outperformed either drug alone in a phase II clinical trial in patients with mixed dyslipidemia.
This agent could fill an unmet need for a safe, convenient, and highly effective therapy for the commonplace lipid profile of high triglyceride, low HDL cholesterol, and high LDL cholesterol levels found among patients with metabolic syndrome or diabetes, Michael Rooney, Ph.D., noted at the annual scientific sessions of the American Heart Association.
LifeCycle Pharma Inc., the Danish company developing the fixed-dose combination tablet, is ironing out the details of a planned pivotal phase III trial with the Food and Drug Administration, Dr. Rooney said in an interview.
The phase II study involved 220 patients with mixed dyslipidemia who were randomized double blind to 12 weeks of the investigational combination of 40 mg of atorvastatin and 100 mg of the proprietary micronized fenofibrate, 40 mg of atorvastatin alone, or 145 mg of the Tricor brand of fenofibrate. Unlike Tricor and generic fenofibrate, the novel micronized formulation of the drug need not be taken with meals.
The combination tablet lowered triglyceride levels by a mean of 49% from a baseline of 270 mg/dL, compared with reductions of 29% and 28%, with atorvastatin and the higher-dose fenofibrate monotherapy, reported Dr. Rooney of Radiant Research, Chicago, a clinical research company contracted to conduct the trial.
The fixed-dose combination also boosted HDL levels 20% from a baseline of 43 mg/dL, compared with a 19% increase with fenofibrate monotherapy and a 7% bump with atorvastatin. From a mean baseline of 164 mg/dL, LDL cholesterol was reduced by a mean of 42% with the combination, 43% with atorvastatin alone, and 14% with 145 mg/day fenofibrate. Levels of apolipoprotein B were reduced from a baseline of 145 mg/dL by 41% with the combination, 37% with atorvastatin alone, and 15% with fenofibrate.
In terms of safety end points, there were five cases of myalgia and other muscle-related problems with atorvastatin monotherapy, four cases with fenofibrate monotherapy, and none in patients on the fixed-dose combination.
Presented at the annual scientific sessions of the American Heart Association, 2008