A Randomized, Double-blind, Placebo Controlled, Crossover Study to Assess Safety and Tolerability, Pharmacokinetics, and Explore Pharmacodynamics of TAP311 in Patients With Mixed Dyslipidaemia

The study will assess the safety, tolerability and pharmacokinetics of TAP311 in patients with dyslipidemia.

Start Date01 Jun 2012

Sponsor / Collaborator

Novartis Pharmaceuticals Canada, Inc.

NCT01487460 / CompletedPhase 1

A First-in-human Randomized, Double-blind, Placebo-controlled, 4-part Study to Assess Safety, Tolerability, Pharmacokinetics (Including Open Label Study of Food Effect and Interaction With Simvastatin) and Pharmacodynamics of Interwoven Single- and Multiple-ascending Doses of TAP311 in Healthy Subjects and Dyslipidemic Patients.

This study will assess the safety, tolerability, and effect of TAP311 on blood lipids in healthy subjects and in patients who have dyslipidemia. The effect of food on TAP311 concentration in blood and effect of TAP311 administration on simvastatin concentration will also be assessed in healthy volunteers.

Start Date01 Nov 2011

Sponsor / Collaborator

Novartis Pharmaceuticals Corp.

100 Clinical Results associated with TAP-311

100 Translational Medicine associated with TAP-311

100 Patents (Medical) associated with TAP-311

Literatures (Medical) associated with TAP-311

26 Oct 2017·Journal of Medicinal ChemistryQ1 · MEDICINE

Discovery of a Novel Piperidine-Based Inhibitor of Cholesteryl Ester Transfer Protein (CETP) That Retains Activity in Hypertriglyceridemic Plasma

Q1 · MEDICINE

Article

Author: Iimura, Akiko ; Yamada, Ken ; Yasoshima, Kayo ; Mitani, Hironobu ; Nonomura, Kazuhiko ; Imase, Hidetomo ; Ohmori, Osamu ; Pan, Meihui ; LaSala, Daniel ; Brousseau, Margaret ; Honma, Wataru ; Mogi, Muneto ; Rigel, Dean F. ; Zhu, Guoming ; Kawanami, Toshio ; Liang, Guiqing ; Iwaki, Yuki ; Umemura, Ichiro

Herein we describe the discovery and characterization of a novel, piperidine-based inhibitor of cholesteryl ester transfer protein (CETP) with a core structure distinct from other reported CETP inhibitors. A versatile synthesis starting from 4-methoxypyridine enabled an efficient exploration of the SAR, giving a lead molecule with potent CETP inhibition in human plasma. The subsequent optimization focused on improvement of pharmacokinetics and mitigation of off-target liabilities, such as CYP inhibition, whose improvement correlated with increased lipophilic efficiency. The effort led to the identification of an achiral, carboxylic acid-bearing compound 16 (TAP311) with excellent pharmacokinetics in rats and robust efficacy in hamsters. Compared to anacetrapib, the compound showed substantially reduced lipophilicity, had only modest distribution into adipose tissue, and retained potency in hypertriglyceridemic plasma in vitro and in vivo. Furthermore, in contrast to torcetrapib, the compound did not increase aldosterone secretion in human adrenocortical carcinoma cells nor in chronically cannulated rats. On the basis of its preclinical efficacy and safety profile, the compound was advanced into clinical trials.

100 Deals associated with TAP-311

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Dyslipidemias	Preclinical	US	Novartis Pharmaceuticals Corp.	01 Nov 2011

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