更新于：2024-06-24
PF-05230907
更新于：2024-06-24
概要
基本信息
药物类型 重组凝血因子 |
别名 FXa、FXAI16L、PF 5230907 + [3] |
作用机制 prothrombin调节剂(凝血酶原调节剂) |
治疗领域 |
在研适应症- |
非在研适应症 |
原研机构 |
在研机构- |
非在研机构 |
最高研发阶段终止临床1期 |
首次获批日期- |
最高研发阶段(中国)- |
特殊审评- |
关联
3
项与 PF-05230907 相关的临床试验A PHASE 1B MULTICENTER, OPEN-LABEL STUDY TO EVALUATE THE SAFETY AND TOLERABILITY AND DETERMINE THE MAXIMUM TOLERATED DOSE OF PF-05230907 IN SUBJECTS WITH INTRACEREBRAL HEMORRHAGE (ICH)
A Phase 1, Randomized, Double-blind, Sponsor-open, Placebo-controlled, Single Ascending Dose Study To Evaluate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of An Intravenous Bolus Infusion Pf-05230907 In Healthy Japanese Subjects
A Phase 1, Randomized, Double-blind, Sponsor-open, Placebo-controlled, Single Ascending Dose Study To Evaluate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Pf-05230907 In Healthy Subjects
100 项与 PF-05230907 相关的临床结果
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100 项与 PF-05230907 相关的转化医学
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100 项与 PF-05230907 相关的专利（医药）
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458
项与 PF-05230907 相关的文献（医药）2024-02-01British journal of anaesthesia
Comparative analysis of andexanet alfa and prothrombin complex concentrate in reversing anticoagulation by rivaroxaban ex vivo
Article
作者: Schöchl, Herbert ; Deventer, Katharina ; Rayatdoost, Farahnaz ; Rossaint, Rolf ; Grottke, Oliver
BACKGROUND:
The comparative effectiveness of the specific antidote andexanet alfa vs the nonspecific therapy four-factor prothrombin complex concentrates (4F-PCCs) as reversal agents for direct factor Xa (FXa) inhibitors in severely bleeding patients is unclear. We hypothesised that specific reversal using andexanet alfa would be more effective than a high dose of PCC (50 IU kg-1) for reversing the FXa inhibitor rivaroxaban.
METHODS:
The reversal potential of andexanet alfa, various 4F-PCCs, and activated PCC was investigated ex vivo in human blood anticoagulated with rivaroxaban (37.5, 75, 150, and 300 ng ml-1) using a panel of coagulation parameters, including conventional coagulation assays, thrombin generation, and a newly developed viscoelastometric device. We simulated in vivo conditions of coagulation activation and fibrin formation using flow chamber experiments of thrombogenicity potential under arterial flow conditions.
RESULTS:
The 4F-PCCs normalised clotting profiles only at low rivaroxaban concentrations, whereas andexanet alfa and activated PCC significantly shortened clotting time at all rivaroxaban concentrations. Only andexanet alfa restored thrombin generation to baseline. Flow chamber results showed that various 4F-PCCs concentration-dependently restored clot formation.
CONCLUSIONS:
In contrast to thrombin generation measurements, haemostatic reversal of rivaroxaban using high-dose 4F-PCCs exhibited similar efficacy as andexanet alfa in flow chamber experiments. The haemostatic effects of 4F-PCCs and andexanet alfa in the context of bleeding patients taking FXa inhibitors requires further study.
2023-12-01American journal of clinical pathology
One-year retrospective analysis of anti-FXa apixaban and rivaroxaban levels demonstrates utility for management decisions in various urgent and nonurgent clinical situations
Article
作者: Grandoni, Jessica ; Sylvester, Katelyn W ; Connors, Jean M ; Battinelli, Elisabeth M ; Ballard, Kathleen ; Sek, Rebecca ; Lucas, Fabienne ; Lewis, Joshua ; Ting, Clara ; Bernier, Thomas D
Abstract:
Objectives:
Quantification of direct oral anticoagulant (DOAC) plasma levels can guide clinical management, but insight into clinical scenarios surrounding DOAC-calibrated anti-FXa assays is limited.
Methods:
Apixaban- and rivaroxaban-calibrated chromogenic anti-Xa assays performed over a 1-year period were retrospectively analyzed. Patient demographics, DOAC history, concomitant medications, and renal/liver comorbidities were obtained. Indications for testing and associated clinical actions were reviewed. Machine learning (ML) models predicting clinical actions were evaluated.
Results:
In total, 371 anti-FXa apixaban and 89 anti-FXa rivaroxaban tests were performed for 259 and 67 patients in recurring urgent (acute bleeding, unplanned procedures) and nonurgent situations, including several scenarios not captured by existing testing recommendations (eg, drug monitoring, recurrent thromboembolic events, bleeding tendency). In urgent settings, andexanet reversal was guided by radiologic and clinical findings over DOAC levels in 14 of 32 instances, while 51% of apixaban patients qualified for nonreversal strategies through the availability of levels. Levels also informed procedure/intervention timing and supported management decisions when DOAC clearance or DOAC target levels were in question. The importance of clinical context was emphasized by exploratory ML models predicting particular clinical actions.
Conclusions:
Although clinical situations are complex, DOAC testing facilitates clinical decision-making, including reversal, justifying more widespread implementation of these assays.
2023-10-01Thrombosis research
In vitro effects of Gla-domainless factor Xa analog on procoagulant and fibrinolytic pathways in apixaban-treated plasma and whole blood
Article
作者: Johnson, Penny M ; Tanaka, Kenichi A ; Butt, Amir L ; Levy, Jerold H ; Terada, Rui ; Stewart, Kenneth E ; Mishima, Yuko
BACKGROUND:
Andexanet alfa is a Gla-domainless FXa (GDXa) analog used as an antidote to FXa inhibitors. Despite its clinical use, laboratory monitoring for anti-Xa reversal and the effect of andexanet on fibrinolysis has not been explored. We used a GDXa with a serine-to-alanine mutation at position 195 (chymotrypsin numbering) to model the interaction between andexanet and apixaban.
METHODS:
Six batches of pooled plasma, and whole blood from healthy volunteers were treated with increasing concentrations of apixaban with/without GDXa. Thrombin generation and plasmin generation (TG and PG) were tested in plasma, and whole blood thrombus formation was tested using thromboelastometry or a flow-chamber system. FXa was also tested in isolation for its ability to support plasmin activation with/without apixaban and GDXa.
RESULTS:
Apixaban (250-800 nM) concentration-dependently decreased the velocity and peak of TG in plasma. Apixaban prolonged the onset of thrombus formation in thromboelastometry and flow-chamber tests. GDXa normalized apixaban-induced delays in TG and whole blood thrombus formation. However, GDXa minimally affected the low PG velocity and peak caused by apixaban at higher concentrations (500-800 nM). FXa promoted plasmin generation independent of fibrin that was inhibited by apixaban at supratherapeutic concentrations.
CONCLUSIONS:
This study demonstrated the feasibility of assessing coagulation lag time recovery in plasma and whole blood following in vitro apixaban reversal using GDXa, a biosimilar to andexanet. In contrast, GDXa-induced changes in plasmin generation and fibrinolysis were limited in PG and tPA-added ROTEM assays, supporting the endogenous profibrinolytic activity of FXa and its inhibition at elevated apixaban concentrations.
100 项与 PF-05230907 相关的药物交易
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研发状态
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 脑出血 | 临床1期 | 美国 | 2016-11-01 | |
| 脑出血 | 临床1期 | 加拿大 | 2016-11-01 | |
| 脑出血 | 临床1期 | 西班牙 | 2016-11-01 | |
| 脑出血 | 临床1期 | 英国 | 2016-11-01 |
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临床结果
临床结果
适应症
分期
评价
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临床1期 | 21 | 衊顧構蓋願築構範簾鏇(鹽醖築繭膚壓獵築構夢) = thromboembolic or ischemic events occurred in the 30 μg/kg dose group 2patirnt 遞選觸窪壓繭鏇壓願繭 (遞網淵糧顧顧鏇觸襯製 ) | 积极 | 2021-01-01 | |||
临床1期 | 21 | (PF-05230907 5 Microgram Per Kilogram (mcg/kg)) | 齋遞膚鹽願齋膚夢襯顧(窪網構顧鬱艱鑰窪襯鏇) = 網餘蓋鹹齋選廠襯鏇齋 築鹽觸鹹構構壓簾醖構 (鹽鑰夢簾窪鑰衊鑰網鹹, 鹽艱鑰夢繭衊構餘鑰築 ~ 襯膚膚憲製膚繭夢獵醖) 更多 | - | 2019-04-17 | ||
(PF-05230907 8 mcg/kg) | 齋遞膚鹽願齋膚夢襯顧(窪網構顧鬱艱鑰窪襯鏇) = 齋網顧餘積壓顧構遞糧 築鹽觸鹹構構壓簾醖構 (鹽鑰夢簾窪鑰衊鑰網鹹, 艱積齋襯蓋鏇鹽鏇淵鬱 ~ 範鹽遞醖淵壓築鹽鬱繭) 更多 |
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