A Site and Subject Blinded Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BMS 852927 in Patients With Primary Hypercholesterolemia on a Stable Dose of Statin Therapy

The purpose of this study is to evaluate the safety of BMS-852927 after 28 days of dosing in patients with high cholesterol.

Start Date01 Nov 2012

Sponsor / Collaborator

Bristol Myers Squibb Co.

100 Clinical Results associated with BMS-852927

100 Translational Medicine associated with BMS-852927

100 Patents (Medical) associated with BMS-852927

Literatures (Medical) associated with BMS-852927

01 Aug 2016·Cell MetabolismQ1 · BIOLOGY

Beneficial and Adverse Effects of an LXR Agonist on Human Lipid and Lipoprotein Metabolism and Circulating Neutrophils

Q1 · BIOLOGY

Article

Author: Sleph, Paul ; Garcia, Ricardo ; Grimm, Denise ; Zhang, Jane ; Malone, Harold ; Shipkova, Petia ; Salvador, Lisa ; Gandhi, Mohit D ; Wang, Zhaoqing ; Lee, John ; Ryan, Carol S ; Zhu, Jun ; Garmise, Robert J ; Martin, Richard ; Mohan, Raju ; Lupisella, John ; Ostrowski, Jacek ; Liu, Xiaoqin ; Zhang, Rongan ; Kick, Ellen ; Frost, Robert J A ; Barrett, Yu Chen ; Behnia, Kamelia ; Li, Tong ; Du, Shuyan ; He, Aiqing ; Wastall, Philip ; Yuan, Long ; Fernando, Gayani ; Cantor, Glenn H ; Kirchgessner, Todd G

The development of LXR agonists for the treatment of coronary artery disease has been challenged by undesirable properties in animal models. Here we show the effects of an LXR agonist on lipid and lipoprotein metabolism and neutrophils in human subjects. BMS-852927, a novel LXRβ-selective compound, had favorable profiles in animal models with a wide therapeutic index in cynomolgus monkeys and mice. In healthy subjects and hypercholesterolemic patients, reverse cholesterol transport pathways were induced similarly to that in animal models. However, increased plasma and hepatic TG, plasma LDL-C, apoB, apoE, and CETP and decreased circulating neutrophils were also evident. Furthermore, similar increases in LDL-C were observed in normocholesterolemic subjects and statin-treated patients. The primate model markedly underestimated human lipogenic responses and did not predict human neutrophil effects. These studies demonstrate both beneficial and adverse LXR agonist clinical responses and emphasize the importance of further translational research in this area.

100 Deals associated with BMS-852927

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Indication	Highest Phase	Country/Location	Organization	Date
Primary hypercholesterolemia	Phase 1	CA	Bristol Myers Squibb Co.	01 Nov 2012
Primary hypercholesterolemia	Phase 1	DE	Bristol Myers Squibb Co.	01 Nov 2012
Atherosclerosis	Phase 1	US	Bristol Myers Squibb Co.	-
Atherosclerosis	Phase 1	-	Exelixis, Inc.	-

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