Clinical Research
Pharmacotherapy of HDL and LDL
Efficacy and Safety of Torcetrapib, a Novel Cholesteryl Ester Transfer Protein Inhibitor, in Individuals With Below-Average High-Density Lipoprotein Cholesterol Levels

https://doi.org/10.1016/j.jacc.2006.06.067Get rights and content
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Objectives

This study was designed to evaluate the efficacy and safety of torcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, in subjects with low high-density lipoprotein cholesterol (HDL-C) levels.

Background

Evidence suggests HDL-C is atheroprotective. A proven mechanism for increasing the level of HDL-C is the inhibition of CETP.

Methods

A total of 162 subjects with below-average HDL-C (men <44 mg/dl; women <54 mg/dl) who were not taking lipid-modifying therapy were randomized to double-blind treatment with torcetrapib 10, 30, 60, or 90 mg/day or placebo (∼30 subjects per group).

Results

The percent change from baseline to Week 8 with torcetrapib (least-squares mean difference from placebo) was dose-dependent and ranged from 9.0% to 54.5% for HDL-C (p ≤ 0.0001 for 30 mg and higher doses) and from 3.0% to −16.5% for low-density lipoprotein cholesterol (LDL-C) (p < 0.01 for 90-mg dose). Low-density lipoprotein cholesterol lowering was less in subjects with higher (>150 mg/dl) versus lower levels of baseline triglycerides; at 60 mg, the change in LDL-C was 0.1% versus −22.2% (p < 0.0001), respectively. Particle size for both HDL and LDL increased with torcetrapib. There were no dose-related increases in the frequency of adverse events. Significant blood pressure increases were noted in 2 of 140 subjects.

Conclusions

Torcetrapib resulted in substantial dose-dependent elevations in HDL-C, accompanied by moderate decreases in LDL-C at the higher doses. Torcetrapib was generally well tolerated.

Abbreviations and Acronyms

AE
adverse event
apo
apolipoprotein
CE
cholesteryl ester
CETP
cholesteryl ester transfer protein
CHD
coronary heart disease
CVD
cardiovascular disease
DBP
diastolic blood pressure
HDL-C
high-density lipoprotein cholesterol
LDL-C
low-density lipoprotein cholesterol
NMR
nuclear magnetic resonance
SBP
systolic blood pressure
VLDL-C
very low-density lipoprotein cholesterol

Cited by (0)

This study was sponsored by Pfizer Inc. Conflicts of interest: Dr. Michael H. Davidson—Research Grants: Abbott Laboratories, AstraZeneca, KOS, Merck, Merck/Schering Plough, Pfizer, Reliant Pharmaceuticals, Roche, Sankyo Pharma, and Takeda Pharmaceuticals. Speakers’ Bureau: Abbott Laboratories, AstraZeneca, KOS, Merck, Merck/Schering-Plough, Pfizer, Reliant Pharmaceuticals, Sankyo Pharma, and Takeda Pharmaceuticals. Consultant/Advisory Board: Abbott Laboratories, AstraZeneca, KOS, Merck, Merck/Schering-Plough, Pfizer, Reliant Pharmaceuticals, Roche, Sankyo Pharma, Sumimoto Pharmaceuticals, and Takeda Pharmaceuticals. Dr. James M. McKenney—Speaking Honorarium: AstraZeneca, KOS, Merck/Schering Plough, Pfizer, Reliant Pharmaceuticals, and Takeda Pharmaceuticals. Consultant/Advisory Board: AstraZeneca, KOS, Microbia, Pfizer, and Sankyo Pharma. Research Grants (awarded to company, not individual): AstraZeneca, GSK, KOS, Merck, Pfizer, Roche, Schering Plough, and Takeda Pharmaceuticals. Dr. James H. Revkin—Ownership Interest: Pfizer Stock/Options. Institution/Employer: Pfizer. Adjunct Faculty: Yale University. Dr. Charles L. Shear—Institution/Employer: Pfizer.