Trial reportArteriosclerosis, thrombosis, and vascular biology2004
Raising high-density lipoprotein in humans through inhibition of cholesteryl ester transfer protein: an initial multidose study of torcetrapib.
Trial report in Arteriosclerosis, thrombosis, and vascular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
62 citing papers in PubMed, 2 syntheses or guidelines pooled it, 371 citations in OpenAlex.
- Role of apolipoprotein C1 in lipoprotein metabolism, atherosclerosis and diabetes: a systematic review.Cardiovascular diabetology · 2022Pooled it
- Addressing cardiovascular risk beyond low-density lipoprotein cholesterol: the high-density lipoprotein cholesterol story.Current cardiology reports · 2004Pooled it
- Pharmacokinetics, pharmacodynamics and safety of CKD-519, a CETP inhibitor, in healthy subjects.Drug design, development and therapy · 2016Trial
- Single dose pharmacokinetics, pharmacodynamics, tolerability and safety of BAY 60-5521, a potent inhibitor of cholesteryl ester transfer protein.British journal of clinical pharmacology · 2012Trial
- Lack of effect of dalcetrapib on QT interval in healthy subjects following multiple dosing.European journal of clinical pharmacology · 2010Trial
- Single-dose pharmacokinetics and pharmacodynamics of anacetrapib, a potent cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects.British journal of clinical pharmacology · 2009Trial
- Bile Acid and Cholesterol Metabolism in Atherosclerotic Cardiovascular Disease and Therapy.Cardiology plus · 2020Article
- Relationship between gut microbiota and circulating metabolites in population-based cohorts.Nature communications · 2019Article
- Quantitative Prediction of Human Pharmacokinetics and Pharmacodynamics of CKD519, a Potent Inhibitor of Cholesteryl Ester Transfer Protein (CETP).Pharmaceutics · 2019Article
- Cholesteryl Ester Transfer Protein Inhibition for Preventing Cardiovascular Events: JACC Review Topic of the Week.Journal of the American College of Cardiology · 2019Review
- Antidyslipidemic potential of a novel farnesoid X receptor antagonist in a hamster model of dyslipidemia: Comparative studies of other nonstatin agents.Pharmacology research & perspectives · 2018Article
- CETP Inhibition: Past Failures and Future Hopes.Clinical Medicine Insights. Cardiology · 2016Review
- An in-silico model of lipoprotein metabolism and kinetics for the evaluation of targets and biomarkers in the reverse cholesterol transport pathway.PLoS computational biology · 2014Article
- Treating low high-density lipoprotein cholesterol: what is the evidence?Therapeutic advances in endocrinology and metabolism · 2014Review
- Monogenic causes of elevated HDL cholesterol and implications for development of new therapeutics.Clinical lipidology · 2013Article
- Plasma lipid transfer proteins and cardiovascular disease. The Framingham Heart Study.Atherosclerosis · 2013Article
- Structural features of cholesteryl ester transfer protein: a molecular dynamics simulation study.Proteins · 2013Article
- Postprandial changes in high density lipoproteins in rats subjected to gavage administration of virgin olive oil.PloS one · 2013Article
- Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach.BMC systems biology · 2012Article
- A physiologically based in silico kinetic model predicting plasma cholesterol concentrations in humans.Journal of lipid research · 2012Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe ability of the potent cholesteryl ester transfer protein (CETP) inhibitor torcetrapib (CP-529,414) to raise high-density lipoprotein cholesterol (HDL-C) levels in healthy young subjects was tested in this initial phase 1 multidose study. METHODS AND
resultsFive groups of 8 subjects each were randomized to placebo (n=2) or torcetrapib (n=6) at 10, 30, 60, and 120 mg daily and 120 mg twice daily for 14 days. Torcetrapib was well tolerated, with all treated subjects completing the study. The correlation of plasma drug levels with inhibition (EC50=43 nM) was as expected based on in vitro potency (IC50 approximately 50 nM), and increases in CETP mass were consistent with the proposed mechanism of inhibition. CETP inhibition increased with escalating dose, leading to elevations of HDL-C of 16% to 91%. Total plasma cholesterol did not change significantly because of a reduction in nonHDL-C, including a 21% to 42% lowering of low-density lipoprotein cholesterol at the higher doses. Apolipoprotein A-I and E were elevated 27% and 66%, respectively, and apoB was reduced 26% with 120 mg twice daily. Cholesteryl ester content decreased and triglyceride increased in the nonHDL plasma fraction, with contrasting changes occurring in HDL.
conclusionsThese effects of CETP inhibition resemble those observed in partial CETP deficiency. This work serves as a prelude to further studies in subjects with low HDL, or combinations of dyslipidemia, in assessing the role of CETP in atherosclerosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.