Heart Drug Combo Reduces "Flushing"
Merck reported positive results from a phase III trial of Cordaptive for the treatment of dyslipidemia. Cordaptive was shown to lower LDL --or bad -- cholesterol and raise HDL -- or good -- cholesterol, while lowering some of the side effects of such drugs.
The drug is a combination of extended-release niacin and an investigative compound called laropiprant (MK-0524). laropiprant is an inhibitor of niacin-induced flushing, a common side effect of some cholesterol drugs. The combo is being investigated for the prevention of coronary heart disease (CHD, coronary artery disease) and atherosclerosis.
The double-blind, randomized trial enrolled 1,613 subjects who received Cordaptive (1 gram/day), extended-release niacin alone (1 gram/day) or placebo. After four weeks, the active treatment groups doubled their respective doses to 2 grams per day for an additional 20 weeks.
The co-primary endpoints were the effects of 2 grams of Cordaptive versus placebo on percent changes in LDL-cholesterol (LDL-C) across weeks 12 to 24, and the effects of 1 gram of Cordaptive versus extended-release niacin on flushing symptom severity during the first week of treatment. In the subjects who advanced to 2 grams of Cordaptive, LDL-C levels were reduced from baseline by an average of 19% (versus a reduction of 0.5% with placebo). In addition, in the subjects receiving 1 mg of Cordaptive, 69% reported either no flushing symptoms or mild flushing symptoms during the first week of treatment compared to 44% of those who received extended-release niacin alone.
Secondary endpoints included the effects of 2 grams of Cordaptive versus placebo on HDL-cholesterol (HDL- C) levels, triglyceride levels and other lipid parameters, and the flushing frequency and intensity of 2 grams of Cordaptive compared to extended-release niacin alone. In the subjects receiving Cordaptive 2 mg their HDL-C levels increased by an average of 19% (versus a reduction of 1.2% with placebo), and their triglyceride levels were reduced by an average of 22% (versus an increase of 3.6% with placebo). By week 24, the frequency of moderate or greater flushing was 2 days/week for subjects receiving 2 grams of Cordaptive or a placebo versus 7 days/week among those treated with 2 grams of extended-release niacin.
A New Drug Application (NDA) for Cordaptive for the treatment of dyslipidemia is currently under review by the FDA. A decision is expected by mid 2008.