[Translation] Phase Ic clinical trial of SAR107375E injection in patients with renal failure undergoing hemodialysis to investigate the safety, pharmacokinetics and preliminary pharmacodynamics of dynamically adjusted dosing regimen

主要目的：评估 SAR107375E 注射液在肾功能衰竭患者血液透析的安全性和人体药代动力学（PK）特征；次要目的：探索 SAR107375E 注射液在肾功能衰竭患者血液透析的给药方案；初步探索 SAR107375E 注射液在肾功能衰竭患者血液透析的药效学特征。

[Translation]

Primary purpose: To evaluate the safety and pharmacokinetic (PK) characteristics of SAR107375E injection in patients with renal failure undergoing hemodialysis; Secondary purpose: To explore the dosing regimen of SAR107375E injection in patients with renal failure undergoing hemodialysis; To preliminarily explore the pharmacodynamic characteristics of SAR107375E injection in patients with renal failure undergoing hemodialysis.

Start Date06 Apr 2024

Sponsor / Collaborator

Beijing Kleb Pharmaceutical Development Co., Ltd.

CTR20222815

/ CompletedPhase 1

SAR107375E 注射液在中国健康成年受试者的随机双盲、安慰剂对照、多次静脉推注的安全性、耐受性、药代动力学和初步药效学研究的Ⅰb 期临床试验

[Translation] A Phase Ib randomized, double-blind, placebo-controlled, multiple intravenous push clinical trial of SAR107375E injection in healthy Chinese adult subjects to investigate its safety, tolerability, pharmacokinetics, and preliminary pharmacodynamics

主要目的：评估中国健康成年受试者多次静脉推注（推注时间约 10min）SAR107375E 注射液的安全耐受性和人体药代动力学（PK）特征；次要目的：评估 SAR107375E 注射液多次静脉推注的药效学评价指标及特征。

[Translation]

The primary objective is to evaluate the safety, tolerability and pharmacokinetic (PK) characteristics of SAR107375E injection after multiple intravenous pushes (injection time is approximately 10 minutes) in healthy Chinese adult subjects. The secondary objective is to evaluate the pharmacodynamic evaluation indicators and characteristics of multiple intravenous pushes of SAR107375E injection.

Start Date03 Jan 2023

Sponsor / Collaborator

Beijing Kleb Pharmaceutical Development Co., Ltd.

CTR20211082

/ CompletedPhase 1

SAR107375E注射液在中国健康成年受试者的随机双盲、安慰剂对照、剂量递增、单次静脉推注的安全性、耐受性、药代动力学和初步药效学研究的Ⅰa期临床试验

[Translation] A Phase Ia clinical trial of SAR107375E injection in healthy Chinese adult subjects: a randomized, double-blind, placebo-controlled, dose-escalation, single intravenous push to investigate the safety, tolerability, pharmacokinetics, and preliminary pharmacodynamics

主要目的：评估中国健康成年受试者单次静脉推注（推注时间10min） SAR107375E注射液的安全耐受性；评估中国健康成年受试者单次静脉推注（推注时间10min） SAR107375E注射液的人体药代动力学（PK）特征。次要目的：初步探索SAR107375E注射液的药效学评价指标及特征。

[Translation]

Primary objective: To evaluate the safety and tolerability of SAR107375E injection after a single intravenous injection (injection time 10 minutes) in healthy Chinese adult subjects; To evaluate the human pharmacokinetic (PK) characteristics of SAR107375E injection after a single intravenous injection (injection time 10 minutes) in healthy Chinese adult subjects. Secondary objective: To preliminarily explore the pharmacodynamic evaluation indicators and characteristics of SAR107375E injection.

Start Date09 Jul 2021

Sponsor / Collaborator

Beijing Kleb Pharmaceutical Development Co., Ltd.

100 Clinical Results associated with Segatroxaban

100 Translational Medicine associated with Segatroxaban

100 Patents (Medical) associated with Segatroxaban

Literatures (Medical) associated with Segatroxaban

02 Nov 2023·Expert Opinion on Investigational Drugs

First-in-human trial of SAR107375E, a novel small molecule anticoagulant with dual inhibition of factor Xa and factor IIa

Article

Author: Chen, Guiying ; Li, Chen ; Li, Yongmei ; Wu, Shuanzhi ; Wang, Xiaole ; Zhan, Yaoxuan ; Zheng, Sichao ; Wang, Tenghua ; Li, Xianbo ; Xiao, Shuangshuang ; Liu, Haiyan ; Li, Jieyun ; Wang, Xuan ; Zhang, Zhixin ; He, Jin ; Liang, Xintong ; Jiang, Hongliang ; Ban, Li ; Zou, Qinwen ; Hu, Zhiqin ; Zheng, Qingshan ; Fang, Yi

BACKGROUNDSAR107375E is a direct dual inhibitor of both Factor Xa and Factor IIa and has shown potent anticoagulation activity in vitro and animals. This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending intravenous doses of SAR107375E in healthy Chinese adult subjects.METHODSIn this randomized, double-blind, placebo-controlled trial, 60 healthy Chinese adult subjects were administered intravenously single ascending doses (0.5, 1.5, 3.0, 5.0, 7.5, 10.0, 15.0, or 20.0 mg) of SAR107375E (N = 44) or placebo (N = 16). Plasma and urine concentrations of SAR107375E were measured and used to calculate pharmacokinetic parameters. Coagulation functions were measured and compared with baseline values. Treatment-emergent adverse events were recorded to evaluate safety.RESULTSIn plasma, from the 0.5 to 20.0 mg dose group, t_1/2 is 1.51-4.00 h, C_max is 59.05-1360 ug/L, and AUC_0-t is 25.01-528.45 h*ug/L. And it shows dose proportionality in the 5.0-20.0 mg range. Activated partial thromboplastin time and Ecarin clotting time correlated linearly with drug plasma concentration. No serious adverse events were reported during the study.CONCLUSIONSAR107375E exhibits good safety and tolerability, predictable pharmacokinetics and pharmacodynamics.CLINICAL TRIAL REGISTRATIONwww.chinadrugtrials.org.cn, identifier is CTR20211082.

12 Dec 2013·Journal of Medicinal ChemistryQ1 · MEDICINE

5-Chlorothiophene-2-carboxylic Acid [(S)-2-[2-Methyl-3-(2-oxopyrrolidin-1-yl)benzenesulfonylamino]-3-(4-methylpiperazin-1-yl)-3-oxopropyl]amide (SAR107375), a Selective and Potent Orally Active Dual Thrombin and Factor Xa Inhibitor

Q1 · MEDICINE

Article

Author: Schreuder, Herman ; Follmann, Markus ; Meneyrol, Jerome ; Bono, Françoise ; Altenburger, Jean-Michel ; Klieber, Sylvie ; Herault, Jean-Pascal ; Bocskei, Zsolt ; Rousseaux, Tristan ; Dol, Frederique ; Alet, Nathalie ; Briot, Christophe ; Sadoun, Freddy ; Barre, Guillaume ; Petit, Frederic ; Herbert, Jean-Marc ; Schaeffer, Paul ; Millet, Laurence ; Wehner, Volkmar ; Lassalle, Gilbert ; Florian, Peter

Compound 15 (SAR107375), a novel potent dual thrombin and factor Xa inhibitor resulted from a rational optimization process. Starting from compound 14, with low factor Xa and modest anti-thrombin inhibitory activities (IC50's of 3.5 and 0.39 μM, respectively), both activities were considerably improved, notably through the incorporation of a neutral chlorothiophene P1 fragment and tuning of P2 and P3-P4 fragments. Final optimization of metabolic stability with microsomes led to the identification of 15, which displays strong activity in vitro vs factor Xa and thrombin (with Ki's of 1 and 8 nM, respectively). In addition 15 presents good selectivity versus related serine proteases (roughly 300-fold), including trypsin (1000-fold), and is very active (0.39 μM) in the thrombin generation time (TGT) coagulation assay in human platelet rich plasma (PRP). Potent in vivo activity in a rat model of venous thrombosis following iv and, more importantly, po administration was also observed (ED50 of 0.07 and 2.8 mg/kg, respectively). Bleeding liability was reduced in the rat wire coil model, more relevant to arterial thrombosis, with 15 (blood loss increase of 2-fold relative to the ED80 value) compared to rivaroxaban 2 and dabigatran etexilate 1a.

MoleculesQ3 · CHEMISTRY

Theoretical Study of Molecular Structure and Physicochemical Properties of Novel Factor Xa Inhibitors and Dual Factor Xa and Factor IIa Inhibitors

Q3 · CHEMISTRY

ArticleOA

Author: Remková, Anna ; Remko, Milan ; Broer, Ria

The geometries and energies of factor Xa inhibitors edoxaban, eribaxaban, fidexaban, darexaban, letaxaban, and the dual factor Xa and thrombin inhibitors tanogitran and SAR107375 in both the gas-phase and aqueous solution were studied using the Becke3LYP/6-31++G(d,p) or Grimme’s B97D/6-31++G(d,p) method. The fully optimized conformers of these anticoagulants show a characteristic l-shape structure, and the water had a remarkable effect on the equilibrium geometry. According to the calculated pKa values eribaxaban and letaxaban are in neutral undissociated form at pH 7.4, while fidexaban and tanogitran exist as zwitterionic structures. The lipophilicity of the inhibitors studied lies within a large range of log P between 1 and 4. The dual inhibitor SAR107375 represents an improvement in structural, physicochemical and pharmacokinetic characteristics over tanogitran. At blood pH, SAR107375 predominantly exists in neutral form. In contrast with tanogitran, it is better absorbed and more lipophilic and active after oral application.

100 Deals associated with Segatroxaban

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hemodialysis complication	Phase 1	China	Beijing Kleb Pharmaceutical Development Co., Ltd.	06 Apr 2024
Venous Thromboembolism	Phase 1	China	Beijing Kleb Pharmaceutical Development Co., Ltd.	03 Jan 2023
Venous Thrombosis	Phase 1	China	Beijing Kleb Pharmaceutical Development Co., Ltd.	09 Jul 2021
Thrombosis	Preclinical	France	Sanofi SA	30 Jan 2012

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