An Open-Label, Randomised, Parallel Group Pilot Study to Assess the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Single Doses of DS-1093a in Patients With Chronic Kidney Disease

DS-1093a is an inhibitor of hypoxia-inducible factor prolyl hydroxylases, and is expected to produce transient dose / exposure dependent increases in erythropoietin levels in subjects with chronic kidney disease (CKD). This study will be conducted in 2 parts. Part A will involve subjects with stage 3b or 4 CKD, and will be an open, non-controlled parallel group investigation of three single doses of DS-1093a (6 subjects/dose), in which allocation to dose will be randomised. On completion of this part of the study an optional fourth dose may be tested to gain a more complete understanding of the PK/PD behaviour of DS-1093a. Part B will be an open, non-controlled investigation of a single dose of DS-1093a in CKD subjects (n=6) receiving haemodialysis. The dose for Part B will be determined based on the data from Part A.

开始日期2014-11-01

申办/合作机构

Daiichi Sankyo, Inc.

[+1]

NCT02142400 / Completed临床1期

A Double Blind, Randomised, Placebo-controlled, Multiple Ascending-dose Study to Assess the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of DS 1093a in Healthy Male Subjects

This is a randomised, double-blind, placebo-controlled multiple ascending single study. It is hypothesised that at least dose of DS-1093a will be safe and tolerable over a 2-week treatment period and will result in increases in reticulocyte count and haemoglobin concentrations in healthy male volunteers

开始日期2014-05-01

申办/合作机构

Daiichi Sankyo, Inc.

100 项与 DS-1093 相关的临床结果

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100 项与 DS-1093 相关的转化医学

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100 项与 DS-1093 相关的专利（医药）

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项与 DS-1093 相关的文献（医药）

2024-10-01·BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Discovery of DS-1093a: An oral hypoxia-inducible factor prolyl hydroxylase inhibitor for the treatment of renal anemia

Article

作者: Tsuji, Takashi ; Niitsu, Yoichi ; Ishii, Ken ; Goto, Riki ; Takahashi, Shinichi ; Tanaka, Naoki ; Kuribayashi, Takeshi ; Sasaki, Koji ; Takano, Rieko ; Obayashi, Hisakuni ; Yamaguchi, Kyoji ; Fukuda, Takeshi ; Hashimoto, Masami

Inhibition of the hypoxia-inducible factor prolyl hydroxylase (HIF-PHD) represents a promising strategy for discovering next-generation treatments for renal anemia. We discovered DS44470011 in our previous study, which showed potent in vitro activity and in vivo efficacy based on HIF-PHD inhibition. However, DS44470011 was also found to exert genotoxic effects. By converting the biphenyl structure, which is suspected to be the cause of this genotoxicity, to a 1-phenylpiperidine structure, we were able to avoid genotoxicity and further improve the in vitro activity and in vivo efficacy. Furthermore, through the optimization of pyrimidine derivatives, we discovered DS-1093a, which has a wide safety margin with potent in vitro activity and an optimal pharmacokinetic profile. DS-1093a achieved an increase in hemoglobin levels in an adenine-induced rat model of chronic kidney disease after its continuous administration for 4 days.

100 项与 DS-1093 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
肾性贫血	临床1期	捷克	Daiichi Sankyo, Inc.	2014-11-01
肾性贫血	临床1期	匈牙利	Daiichi Sankyo, Inc.	2014-11-01
慢性肾病	临床1期	捷克	Daiichi Sankyo, Inc.	2014-11-01
慢性肾病	临床1期	匈牙利	Daiichi Sankyo, Inc.	2014-11-01
贫血	临床1期	英国	Daiichi Sankyo, Inc.	2014-05-01