Effectiveness and tolerability of a new lipid-altering agent, gemcabene, in patients with low levels of high-density lipoprotein cholesterol

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Abstract

This study evaluated the efficacy and tolerability of gemcabene, a new lipid-altering agent, in a double-blind, randomized, dose-response study of 161 patients with high-density lipoprotein (HDL) cholesterol of <35 mg/dl and serum triglyceride (TG) levels of either ≥200 (n = 94) or <200 mg/dl (n = 67). After a 6-week, placebo, dietary lead-in period, patients were administered either 150, 300, 600, or 900 mg of gemcabene or placebo once daily for 12 weeks. In the TG ≥200 mg/dl stratum, gemcabene significantly increased serum HDL cholesterol by 18% with corresponding significant increases of 6% in both apolipoprotein A-I and A-II levels at the 150-mg dose. HDL cholesterol levels also increased 12% at the 300-mg dose; however, this did not reach statistical significance. Also, in the TG ≥200 mg/dl stratum, serum TG levels were significantly reduced by 27% and 39% at the 150- and 300-mg doses of gemcabene, respectively. No significant differences were found in serum HDL cholesterol or TG levels in the TG ≥200 mg/dl groups that received 600 or 900 mg of gemcabene, or in TG <200 mg/dl groups administered any dose of gemcabene. However, at these higher 600- and 900-mg doses, gemcabene significantly reduced serum low-density lipoprotein (LDL) cholesterol levels by 15% to 25%, respectively, in both TG strata, with proportionate decreases in the levels of apolipoprotein B. Gemcabene was well tolerated with a frequency of adverse events similar to that of placebo. In conclusion, at the lower doses, gemcabene significantly increased HDL cholesterol and reduced TG serum levels in patients with low HDL cholesterol and TG ≥200 mg/dl. At the higher doses, gemcabene significantly reduced LDL cholesterol levels in all patients with low HDL cholesterol.

Section snippets

Study design

This was a randomized, double-blind, placebo-controlled, parallel group, dose-response multicenter study. The study was conducted at 11 centers in the United States and 1 center in Canada. Institutional review board approval was obtained at each center and every patient was informed of the study, freely consented to participate, and signed an informed consent document. After a 6-week, single-blind placebo, dietary lead-in period conducted according to the National Cholesterol Education Program

Baseline demographics

A total of 161 patients were randomized. Of these patients, 67 had TG levels <200 mg/dl (14 randomized to placebo and 53 to active treatment) and 94 had TG levels ≥200 mg/dl (18 randomized to placebo and 76 to active treatment). Patient characteristics were generally similar across the TG strata (Table 2), with the obvious exception of the lipid parameters (Table 3). The study was completed by 152 patients. Six withdrew due to adverse events and 3 failed to complete the study for administrative

Discussion

This study was conducted to determine the effectiveness and tolerability of a new lipid-altering compound, gemcabene, in a dose-response study, and represents the first published report of the use of gemcabene in human test subjects. The primary efficacy parameter evaluated was the percent change from baseline in serum HDL cholesterol levels, because clinical improvement in HDL cholesterol levels may further reduce coronary heart disease risk above that achieved with LDL cholesterol lowering.5

Acknowledgements

We are indebted to J. Short and B. Shaw for assistance in managing the study and to M. Pressler, J. Nawrocki, and D. Black for their valued contributions to the design, conduct, and interpretation of this trial.

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This study was supported by a grant from Pfizer Global Research and Development, Ann Arbor Laboratories, Ann Arbor, Michigan.

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