Efficacy and safety of the cholesteryl ester transfer protein inhibitor anacetrapib in Japanese patients with dyslipidemia

Teramoto, Tamio; Shirakawa, Masayoshi; Kikuchi, Masashi; Nakagomi, Mariko; Tamura, Satoko; Surks, Howard K.; Sisk, Christine McCrary; Numaguchi, Hirotaka

doi:10.1016/j.atherosclerosis.2013.05.012

Cited by 24 publications

(17 citation statements)

References 31 publications

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“…Given the range of lipid‐altering efficacy and safety, none of the findings from the present study suggest any differences between Japanese and non‐Japanese responses to anacetrapib that would be of clinical consequence. In support of this, the safety and efficacy of anacetrapib in Japanese patients are comparable to in the global studies …”

Section: Discussionsupporting

confidence: 77%

“…The efficacy and safety of anacetrapib was evaluated in the R andomized EV aluation of the E ffects of A nacetrapib through L ipid modification (REVEAL) trial; anacetrapib lowered the incidence of major coronary events. Anacetrapib, as monotherapy or coadministered with atorvastatin, produced significant reductions in LDL‐C and increases in HDL‐C in Japanese patients with dyslipidemia . More recently, Arai et al (2016) reported on a multicenter, randomized, double‐blind, placebo‐controlled study that assessed the lipid‐modifying efficacy/safety profile of anacetrapib 100 mg added to ongoing statin ± other lipid‐modifying therapies in Japanese patients with heterozygous familial hypercholesterolemia and showed that treatment with anacetrapib 100 mg for 12 weeks resulted in substantial reductions in LDL‐C and increases in HDL‐C and was well tolerated.…”

mentioning

confidence: 99%

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Pharmacokinetics and Pharmacodynamics of Anacetrapib Following Single Doses in Healthy, Young Japanese and White Male Subjects

Krishna

Gheyas

Liu

et al. 2017

The Journal of Clinical Pharma

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Anacetrapib is a cholesteryl ester transfer protein (CETP) inhibitor being developed for the treatment of mixed dyslipidemia. The aim of the study was to evaluate the pharmacokinetic, pharmacodynamic, and safety characteristics of anacetrapib following single doses in healthy, young Japanese men. In a double-blind, randomized, placebo-controlled, 3-panel, single-rising-dose study, 6 healthy young Japanese male or white male subjects (aged 19 to 44 years) received single oral doses of 5 to 500 mg anacetrapib, and 2 received placebo. Plasma and urine drug concentrations were measured 0-168 hours postdose, and plasma CETP inhibition was measured 0-24 hours postdose. Urinary anacetrapib levels were all below quantitation limits. Plasma concentrations of anacetrapib increased approximately less than dose-proportionally. Consumption of a traditional Japanese breakfast prior to dosing increased the plasma pharmacokinetics of anacetrapib in Japanese subjects compared with fasted conditions, to a similar extent as in white subjects. CETP activity measured over 0-24 hours postdose resulted in significant inhibition. Anacetrapib was generally well tolerated, and there were no serious adverse experiences. No clinically meaningful differences in PK and CETP inhibition parameters were found between Japanese and white subjects.

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Section: Discussionsupporting

confidence: 77%

mentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Anacetrapib Following Single Doses in Healthy, Young Japanese and White Male Subjects

Krishna

Gheyas

Liu

et al. 2017

The Journal of Clinical Pharma

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“…In this study, FAMP enhanced RCT in both WT and CETP-Tg mice, which indicates that FAMP improved RCT. Although CETP collects TG from very-low-density lipoprotein or LDL and exchanges them for cholesteryl esters from HDL, and CETP inhibition increases HDL-C levels [4][5][6][7], it is not an important mechanism of FAMP for enhancing RCT. There is another mechanism for enhancing RCT by FAMP.…”

Section: Discussionmentioning

confidence: 97%

“…Although HDL is a target in the treatment of atherosclerotic CVD, there are currently only a limited number of therapeutic options to increase and enhance the function of HDL. Therapeutic strategies that use cholesterol ester transfer protein (CETP) inhibitors (torcetrapib, dalcetrapib, anacetrapib and evacetrapib) have recently been described [4][5][6][7], but none are clinically available yet.…”

Section: Introductionmentioning

confidence: 99%

Newly developed apolipoprotein A-I mimetic peptide promotes macrophage reverse cholesterol transport in vivo

Shimizu

Tanigawa

Miura

et al. 2015

International Journal of Cardiology

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“…Inhibitors of the cholesterol ester transfer protein (CETP) increasing HDL-c and reducing LDL-c are not approved yet. In a phase-2 trial Anazetrapib additionally lowered Lp(a) by 50% [34]. In the REALIZE trial Anazetrapib showed a substantial reduction of Lp(a) by 31.8% in patients with heterozygous familial hypercholesterolaemia (FH) [35].…”

Section: Emerging Therapiesmentioning

confidence: 99%

Hyperlipoproteinaemia(a) – apheresis and emerging therapies

Vogt

2017

Clin Res Cardiol Suppl

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A high level of lipoprotein(a) (Lp(a)) is recognized as an independent and additional cardiovascular risk factor contributing to the risk of early onset and progressive course of cardiovascular disease (CVD). All lipid lowering medications in use mainly lower low density lipoprotein-cholesterol (LDL-c) with no or limited effect on levels of Lp(a). Niacin, the only component lowering Lp(a), is firstly often poorly tolerated and secondly not available anymore in many countries. A level of <50 mg/dl was recommended recently as the cut off level for clinical use and decision making. Since lipoprotein apheresis (LA) lowers not only LDL-c but also Lp(a) significantly, its use is recommended in some countries in very high-risk patients with early or progressive CVD. Retrospective analyses show that regular LA improves the course of CVD. This is supported by a recent prospective observational trial and data of the German Lipoprotein Apheresis Registry. Despite many treatment options, all too often it is not possible to reduce LDL-c levels to target and to reduce Lp(a) levels sustainably at all. Therefore, new drug therapies are awaited. Some of the lipid modifying drugs in development lower Lp(a) to some extent in addition to LDL-c; the only specific approach is the apoprotein(a) antisense oligonucleotide. Currently LA is the standard of care as a last resort treatment in high-risk patients with elevated Lp(a) and severe CVD despite optimal control of all other cardiovascular risk factors.

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Efficacy and safety of the cholesteryl ester transfer protein inhibitor anacetrapib in Japanese patients with dyslipidemia

Cited by 24 publications

References 31 publications

Pharmacokinetics and Pharmacodynamics of Anacetrapib Following Single Doses in Healthy, Young Japanese and White Male Subjects

Pharmacokinetics and Pharmacodynamics of Anacetrapib Following Single Doses in Healthy, Young Japanese and White Male Subjects

Newly developed apolipoprotein A-I mimetic peptide promotes macrophage reverse cholesterol transport in vivo

Hyperlipoproteinaemia(a) – apheresis and emerging therapies

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