Phase I, Randomized, Double-Blind, Placebo-Controlled, Ascending Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AMG 333 in Healthy Subjects and Migraine Subjects

The primary purpose of this study is to evaluate the safety and tolerability of multiple oral doses of AMG 333 for 14 days in healthy subjects and migraine subjects. As part of the secondary objectives, the study will characterize the pharmacokinetic (PK) profile of AMG 333 after multiple oral doses in healthy subjects and migraine subjects, as well as characterize the effect of multiple doses of AMG 333 on increases in blood pressure (BP) induced by the cold pressor test (CPT) in healthy subjects.

开始日期2014-05-01

申办/合作机构

Amgen, Inc.

NCT01953341 / Completed临床1期

A Randomized, Double-Blind, Placebo-Controlled, Single-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AMG 333 in Healthy Subjects and Subjects With Migraines.

The primary purpose of this study is to determine whether AMG 333 is safe and well tolerated in healthy subjects and subjects with migraines. As part of the secondary objectives, this study will characterize the pharmacokinetic (PK) profile of AMG 333, as well as characterize the effect of AMG 333 on the cold pressor test (CPT)-induced increase in blood pressure after single oral doses in healthy subjects and subjects with migraines

开始日期2013-10-01

申办/合作机构

Amgen, Inc.

100 项与 AMG-333 相关的临床结果

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100 项与 AMG-333 相关的转化医学

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100 项与 AMG-333 相关的专利（医药）

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项与 AMG-333 相关的文献（医药）

2018-09-27·Journal of medicinal chemistry1区 · 医学

Discovery of TRPM8 Antagonist (S)-6-(((3-Fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)carbamoyl)nicotinic Acid (AMG 333), a Clinical Candidate for the Treatment of Migraine

1区 · 医学

Article

作者: Chen, Jian Jeffrey ; Liu, Qingyian ; Harried, Scott ; Youngblood, Beth D. ; Gore, Vijay K. ; Allen, Jennifer R. ; Horne, Daniel B. ; Davis, Carl D. ; Clarine, Jeffrey ; Biswas, Kaustav ; Lehto, Sonya G. ; Horner, Michelle ; Zhong, Wenge ; Yuan, Chester C. ; Bartberger, Michael D. ; Monenschein, Holger ; Kaller, Matthew R. ; Nguyen, Thomas T. ; Gavva, Narender R. ; Zhang, Maosheng ; Brown, James ; Ma, Vu V.

Transient-receptor-potential melastatin 8 (TRPM8), the predominant mammalian cold-temperature thermosensor, is a nonselective cation channel expressed in a subpopulation of sensory neurons in the peripheral nervous system, including nerve circuitry implicated in migraine pathogenesis: the trigeminal and pterygopalatine ganglia. Genomewide association studies have identified an association between TRPM8 and reduced risk of migraine. This disclosure focuses on medicinal-chemistry efforts to improve the druglike properties of initial leads, particularly removal of CYP3A4-induction liability and improvement of pharmacokinetic properties. A novel series of biarylmethanamide TRPM8 antagonists was developed, and a subset of leads were evaluated in preclinical toxicology studies to identify a clinical candidate with an acceptable preclinical safety profile leading to clinical candidate AMG 333, a potent and highly selective antagonist of TRPM8 that was evaluated in human clinical trials.

100 项与 AMG-333 相关的药物交易

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