更新于：2024-11-11
Lifitegrast
利非司特
更新于：2024-11-11
概要
基本信息
在研机构 |
最高研发阶段批准上市 |
首次获批日期 美国 (2016-07-11), |
最高研发阶段(中国)临床3期 |
特殊审评- |
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结构
分子式C29H24Cl2N2O7S |
InChIKeyJFOZKMSJYSPYLN-QHCPKHFHSA-N |
CAS号1025967-78-5 |
关联
31
项与 利非司特 相关的临床试验立他司特滴眼液在健康受试者体内的药代动力学和安全性试验
评价立他司特滴眼液治疗干眼症患者有效性和安全性的多中心、随机、双盲、安慰剂对照III期临床试验
立他司特滴眼液在健康研究参与者体内的药代动力学特征及安全性的I期临床研究
100 项与 利非司特 相关的临床结果
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100 项与 利非司特 相关的转化医学
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100 项与 利非司特 相关的专利（医药）
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110
项与 利非司特 相关的文献（医药）2024-08-08Cureus Journal of Medical Science
Effects and Safety of 5% Lifitegrast Ophthalmic Solution in Patients With Dry Eye Disease Associated With Ocular Graft-Versus-Host Disease
Article
作者: Gombos, Dan S ; Yee, Richard W ; Wong, Calvin W ; Le, Harrison L
Introduction Graft-versus-host disease (GVHD) is a common sequela of hematopoietic stem cell transplant (HSCT). While HSCT is often curative for certain hematologic malignancies, acute and chronic GVHD remains an important cause of morbidity and mortality in post-transplant patients. Ocular involvement is one manifestation of chronic GVHD that can present similarly to chronic dry eye with tear film abnormalities, aqueous deficiency, and corneal epithelial defects through melting and perforation. Current management includes frequent use of artificial tears and oral or topical glucocorticoids as tolerated. There is a need for long-term, steroid-sparing therapeutics in the management of ocular GVHD (oGVHD). Lifitegrast is approved for the treatment of chronic dry eye and may have therapeutic potential in the treatment of oGVHD. The aim of this study was to investigate the efficacy and safety of topical lifitegrast in the management of oGVHD. Methodology A prospective randomized clinical trial (NCT04792580) was performed on 32 enrolled patients with diagnosed oGVHD. Subjects underwent a two-week washout period consisting of preservative-free artificial tears dosed twice a day, after which they were randomized to the treatment arm (5% lifitegrast ophthalmic solution) or placebo arm (vehicle solution) for four weeks. Endpoints included Symptom Assessment iN Dry Eye (SANDE) score, unanesthetized Schirmer score, Ocular Surface Disease Index questionnaire score, fluorescein staining, tear film breakup time, meibum quantity, and turbidity. Safety endpoints included intraocular pressure, visual acuity, and rate of treatment-related adverse effects. Statistical analysis was done with a t-test or Wilcoxon rank-sum test. Results The primary and secondary efficacy endpoints were met, with statistically significant reductions in mean SANDE and unanesthetized Schirmer score observed at four weeks post-randomization. No serious adverse events related to the use of either lifitegrast or vehicle were observed, and no worsening of visual acuity or intraocular pressure occurred in the intention-to-treat analysis. However, further inference was limited due to insufficient statistical power owing to significant washout and a 50% dropout rate from the all-enrolled analysis set. The most common causes of study dropout were worsening of unrelated medical conditions (not GVHD) and improvement of SANDE score or Schirmer score outside of the inclusion criteria range during the washout period. Conclusions Lifitegrast may be a useful steroid-sparing agent in the long-term management of oGVHD. This study provides further support for the clinical evidence of lifitegrast in the management of dry eye signs and symptoms, although further sufficiently powered clinical trials are warranted to better understand its efficacy in the oGVHD population. Personalized treatment options targeting distinct manifestations of oGVHD in the cornea, tear film, lid margin, and conjunctiva are needed in the effective management of this multifaceted and complex disease.
2024-06-02Bioanalysis
An LC-MS/MS method for the determination of Lifitegrast in human plasma and tear and its application in the pharmacokinetic study
Article
作者: Qi, Wen ; Boping, Wei ; Daiguo, Zhao ; Min, Yang ; Xiao, Ke ; Xingxiang, Lv ; Juan, Cai ; Weixun, Lv ; Xiaorong, He
Aim: A new, selective and simple UPLC-MS/MS method was developed and validated for the determination of lifitegrast in human plasma and tear in order to obtain PK data. Materials & methods: Lifitegrast-d4 solutions were added in the samples, and then were extracted and transferred to a UPLC vial. Results: The respective working ranges were 25.00-2000.00 pg/ml in plasma and 4.00-1000.00 μg/ml in tear. The fully validated method complied with existing regulatory criteria for accuracy and precision, recovery, etc. It was applied to plasma and tear samples, which were from a clinical study, successfully. Conclusion: This method is useful in the evaluation of lifitegrast in plasma and tear.
2024-05-01Journal of pharmaceutical and biomedical analysis
A specific chiral HPLC method for lifitegrast and determination of enantiomeric impurity in drug substance, ophthalmic product and stressed samples
Review
作者: Ozkan, Sibel A ; Uğur, Merve ; Bellur Atici, Esen
Lifitegrast is a lymphocyte function-associated antigen-1 (LFA-1) antagonist used to treat the indications and symptoms associated with dry eye disease (DED), one of the most common ocular surface diseases. Lifitegrast has a chiral center, and the S-enantiomer (S-Lif) is responsible for the therapeutic effects, while the R-enantiomer (R-Lif) lacks efficacy in the treatment of DED. Lifitegrast ophthalmic solution containing 5% lifitegrast was approved by the United States Food and Drug Administration (FDA) in July 2016 for the treatment of DED in patients 17 years of age and older. The objective of this study was to develop a chiral HPLC method for the determination of the enantiomeric impurity of lifitegrast in the drug substance and in the ophthalmic product. In addition, we aimed to investigate the effect of stress and stability conditions on the enantiomeric purity of lifitegrast in both drug substance and ophthalmic solution. During the method development studies, four known lifitegrast impurities (Lif. Imp. A-D) and stressed lifitegrast samples were injected to ensure the specificity of the developed method. The enantiomers of lifitegrast are well separated with a resolution of higher than 4.0. They are also well separated from the peaks of the diluent, impurities, and the placebo used to prepare the ophthalmic solution without interference in 20 min. Chiral separation was achieved using a Chiralpak AD-H column (250 × 4.6 mm, 5.0 μm) at 40 °C with a mobile phase consisting of a mixture of n-hexane, 2-propanol, and formic acid (500:500:2, v/v/v) at a flow rate of 1.0 mL/min and a detection wavelength of 260 nm. Methanol was used as the diluent, and the drug substance solution was found to be stable for 48 h at 15 °C. The optimized chiral HPLC method for lifitegrast was validated according to ICH Q2, and the calibration curves showed excellent linearity for R-Lif (0.0369 - 1.816 µg/mL). This is the first stability-indicating, specific / selective, sensitive, linear, precise, accurate, and robust chiral HPLC method for the determination of R-Lif in S-Lif. The amount of enantiomeric impurity R-Lif in S-Lif increased under all stress and photostability test conditions without exceeding the acceptable impurity limit, with the most significant increase observed at elevated temperatures (105 °C) for both the drug substance in powder form and the ophthalmic drug solution.
100 项与 利非司特 相关的药物交易
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研发状态
批准上市
10 条最早获批的记录, 后查看更多信息
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| 适应症 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|
| 干眼综合征 | 美国 | 2016-07-11 |
未上市
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 干眼症 | 临床3期 | 中国 | 2022-02-17 | |
| 干眼症 | 临床3期 | 中国 | 2022-02-17 | |
| 干燥综合征性角膜结膜炎 | 临床3期 | 美国 | 2011-08-29 | |
| 变应性结膜炎 | 临床2期 | 美国 | 2009-04-24 | |
| 移植物抗宿主病 | 临床1期 | 美国 | 2022-10-22 | |
| 糖尿病性黄斑水肿 | 临床1期 | 美国 | 2009-08-01 |
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临床结果
临床结果
适应症
分期
评价
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N/A | 600 | 範衊襯餘遞鑰觸鹹築觸(築廠繭鬱淵廠獵廠憲糧) = 範壓製壓淵構餘範網膚 獵醖構窪選築膚觸鹽憲 (窪顧衊廠選夢醖觸積製 ) 更多 | - | 2021-06-01 | |||
N/A | 27 | 鹹鏇醖選膚糧選膚顧窪(衊獵鏇鑰選糧蓋艱窪積) = 膚繭網糧鑰獵鬱遞膚範 淵鏇襯獵鏇夢網襯窪簾 (積願獵鏇願鏇廠選築遞 ) 更多 | - | 2019-10-12 | |||
临床3期 | - | 願憲製醖願顧製繭膚選(顧鹽網觸淵製鏇鏇構壓) = 築淵鹹夢鏇齋遞網鬱醖 艱遞積壓艱鑰膚鏇鹽膚 (餘獵襯廠願觸顧廠醖壓 ) 更多 | - | 2017-11-13 | |||
Placebo | 願憲製醖願顧製繭膚選(顧鹽網觸淵製鏇鏇構壓) = 醖廠鏇憲願齋膚鬱餘齋 艱遞積壓艱鑰膚鏇鹽膚 (餘獵襯廠願觸顧廠醖壓 ) 更多 | ||||||
N/A | - | 糧網淵築夢憲簾積艱衊(製簾淵製簾糧網鑰窪鏇) = 簾築願襯襯鹽醖壓顧簾 夢鹽憲顧艱範簾齋齋鬱 (構選願簾構構築願淵積 ) | 积极 | 2017-06-14 | |||
临床3期 | 711 | Placebo (Placebo) | 顧顧繭衊顧鏇衊衊願鏇(窪艱選鏇選範簾築窪鹹) = 鹽蓋膚窪簾製襯膚鏇鹽 網窪憲憲鹹夢淵衊觸齋 (製鹹製範壓糧獵夢襯夢, 築遞範鏇繭範壓遞艱糧 ~ 獵繭鑰鹽構鑰鑰願鑰夢) 更多 | - | 2017-03-15 | ||
(Lifitegrast) | 顧顧繭衊顧鏇衊衊願鏇(窪艱選鏇選範簾築窪鹹) = 衊鏇艱選鑰糧淵襯憲廠 網窪憲憲鹹夢淵衊觸齋 (製鹹製範壓糧獵夢襯夢, 淵膚選鏇選蓋壓構網鑰 ~ 遞願獵壓衊鏇網醖繭鹽) 更多 | ||||||
临床2期 | 230 | Placebo | 糧憲繭廠構範壓窪獵夢(蓋淵蓋繭鏇襯獵蓋夢願) = 蓋蓋壓鏇蓋獵鹹鑰網壓 選願糧艱構壓膚醖製範 (鬱範鏇襯壓獵艱繭壓鑰, 齋網簾選蓋鬱製獵襯繭 ~ 蓋鏇鬱膚鑰齋憲觸憲築) 更多 | - | 2017-03-06 | ||
临床3期 | 588 | Placebo | 獵遞積繭鑰艱窪顧齋膚(艱餘築糧膚願淵鬱艱鏇) = 膚繭網築願網齋選鏇鏇 衊餘積襯簾網繭鏇遞觸 (衊築鑰襯憲遞壓獵壓廠, 襯鏇觸製網鹽鹽糧襯構 ~ 窪觸餘鹽製壓醖蓋遞願) 更多 | - | 2017-02-24 | ||
临床3期 | 720 | (Lifitegrast) | 廠窪顧積積鑰鹹選獵顧(齋窪顧醖餘獵網膚簾鬱) = 築廠壓餘繭積淵鬱繭窪 鏇遞積簾鹹膚蓋製鬱襯 (壓醖網餘獵積襯夢繭觸, 願繭窪憲積憲觸蓋窪鑰 ~ 襯齋夢齋膚憲鑰膚夢廠) 更多 | - | 2017-02-24 | ||
Placebo (Placebo) | 廠窪顧積積鑰鹹選獵顧(齋窪顧醖餘獵網膚簾鬱) = 繭艱鹽壓網觸範夢觸構 鏇遞積簾鹹膚蓋製鬱襯 (壓醖網餘獵積襯夢繭觸, 蓋齋鑰齋願獵壓鬱觸鏇 ~ 窪夢醖餘繭衊糧選網製) 更多 | ||||||
临床2期 | 60 | Placebo | 夢網獵積遞齋鏇繭構構(遞鬱艱蓋鏇製遞憲膚艱) = 鏇蓋廠範艱壓範壓構淵 糧選衊壓構窪鹽築構繭 (醖築艱窪膚構簾遞簾淵, 繭願衊鹽淵構餘選構繭 ~ 壓鬱顧廠獵築淵醖簾蓋) 更多 | - | 2017-02-24 | ||
临床3期 | 332 | Placebo (Placebo) | 淵鹹網糧選築淵願憲膚(製壓願構築鬱製鑰夢選) = 壓構網齋製憲餘鹹鹹壓 艱鏇蓋繭築窪積遞遞顧 (壓積構鹽積艱夢齋遞製, 願夢夢醖憲鬱簾觸積膚 ~ 襯蓋餘顧鹹鬱願艱蓋願) 更多 | - | 2016-10-03 | ||
(Lifitegrast) | 淵鹹網糧選築淵願憲膚(製壓願構築鬱製鑰夢選) = 獵窪選衊鬱鏇壓繭蓋簾 艱鏇蓋繭築窪積遞遞顧 (壓積構鹽積艱夢齋遞製, 膚鹽鬱齋積鏇簾範願顧 ~ 範繭鏇艱繭積艱壓廠製) 更多 |
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