Artefenomel Mesylate(Artefenomel Mesylate) - 在研适应症：疟疾_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点-

作用机制-

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

Clinical Network Services Pty Ltd.Q-Pharm Pty Ltd.

最高研发阶段临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C28H39NO5

InChIKeyXLCNVWUKICLURR-VFXIDCLRSA-N

CAS号1029939-86-3

关联

19

项与 Artefenomel Mesylate 相关的临床试验

NCT03660839 / Completed临床2期

A Randomized, Open Label, Parallel-group, Single Dose Regimen, Phase 2a Study, to Investigate the Clinical and Parasiticidal Activity and the Pharmacokinetics of 3 Dose Levels of Artefenomel (OZ439) Given in Combination With Ferroquine (FQ) and FQ Alone, in African Patients With Uncomplicated Plasmodium Falciparum Malaria

Primary Objective:
To show the contribution of artefenomel (OZ439) to the clinical and parasiticidal effect of OZ439/Ferroquine (FQ) combination by analyzing exposure-response of OZ439 measured by Day 28 polymerase chain reaction (PCR)-corrected adequate clinical and parasitological response (ACPR) for the effect and the area under the curve (AUC) of OZ439 as pharmacokinetic (PK) predictor.
Secondary Objectives:
To evaluate the exposure-response of OZ439 combined with FQ on crude Day 28 ACPR.
To evaluate the dose response of OZ439 combined with FQ on PCR-corrected and crude Day 28 ACPR.
To evaluate the dose-response of OZ439 combined with FQ on selected secondary endpoints.
To evaluate the safety and tolerability of different dosages of OZ439 in combination with FQ and FQ alone.
To characterize the PK of OZ439 in plasma, and of FQ and its active metabolite SSR97213 in blood.

开始日期2018-09-11

申办/合作机构

Sanofi

[+1]

NCT03542149 / Completed临床1期IIT

Phase 1b to Assess Safety, Tolerability, Pharmacokinetic Profile, and Antimalarial Activity of Single Doses of Co-administered OZ439and PQP Against Early Plasmodium Falciparum Blood Stage Infection in Healthy Adult Volunteers

A single-centre Phase 1b study to assess the safety, tolerability, pharmacokinetic profile, and antimalarial activity of single doses of coadministered artefenomel (OZ439) and piperaquine phosphate (PQP) against early Plasmodium falciparum blood stage infection in healthy adult volunteers.

开始日期2018-04-23

申办/合作机构

MMV Medicines for Malaria Venture

[+3]

NCT04069221 / Completed临床1期IIT

An Open-label, Two-part Study to Determine the Absolute Bioavailability (BA) of OZ439 Using Simultaneous Intravenous [14C]-OZ439 Microdose/800mg Oral Dosing and to Investigate the Pharmacokinetics (PK) of OZ439 Granules Administered as Single Doses Suspended in Different Volumes and When Co-administered With a Single Dose of Cobicistat, a Strong CYP3A4 Inhibitor, to Healthy Subjects in Fasted State

This study is an open-label, two-part study to determine the absolute bioavailability (BA) of OZ439 using simultaneous intravenous [14C]-OZ439 microdose/800mg oral dosing and to investigate the pharmacokinetics (PK) of OZ439 granules administered as single doses suspended in different volumes and when co-administered with a single dose of Cobicistat, a strong CYP3A4 inhibitor, to healthy subjects in fasted state.

开始日期2017-02-28

申办/合作机构

MMV Medicines for Malaria Venture

100 项与 Artefenomel Mesylate 相关的临床结果

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100 项与 Artefenomel Mesylate 相关的转化医学

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100 项与 Artefenomel Mesylate 相关的专利（医药）

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65

项与 Artefenomel Mesylate 相关的文献（医药）

2024-10-10·ACS Medicinal Chemistry Letters

Synthesis and In Vivo Profiling of Desymmetrized Antimalarial Trioxolanes with Diverse Carbamate Side Chains

Article

作者: Rosenthal, Philip J. ; Legac, Jenny ; Renslo, Adam R. ; Jaishankar, Priyadarshini ; Kim, Julie ; Gonciarz, Ryan L. ; Cheng, Ke ; Klope, Matthew T. ; Tapia Cardona, Juan A. ; Chen, Jun

The recent withdrawal of artefenomel from clinical development leaves no endoperoxide-class agents in the antimalarial pipeline. Synthetic endoperoxides with a desymmetrized structure have demonstrated promising physiochemical and in vivo properties. Here we expand on our initial investigation of trans-3″ carbamate substitution with a diverse array of amine-, alcohol-, and sulfinyl-terminated analogues prepared in (S,S) and (R,R) configurations. In general, this chemotype combines low-nM antiplasmodial activity with excellent aqueous solubility but widely varying human liver microsome (HLM) stability. We evaluated 20 novel analogues in the P. berghei mouse malaria model, identifying new analogues such as RLA-4767 (9a) and RLA-5489 (9d), with HLM stability and pharmacokinetic profiles superior to analogues from our initial report (e.g., RLA-4776, 8a). These new leads approach or equal the efficacy of artefenomel after two daily oral doses of 10 mg/kg, thus revealing a promising chemotype with the potential to deliver development candidates.

2024-03-01·Headache: The Journal of Head and Face Pain

A randomized, open‐label, 5‐period crossover study evaluating the pharmacokinetics and safety of a single dose of intranasal dihydroergotamine (DHE) powder (STS101), intramuscular DHE mesylate, and liquid nasal spray DHE in healthy adults

Article

作者: Bermudez, Maria ; Levy, Jeff ; Lipton, Richard B. ; Hussey, Elizabeth ; Albrecht, Detlef ; Hu, Jerry

AbstractObjectiveTo compare the safety and pharmacokinetics (PK) of dihydroergotamine (DHE) after administration of intranasal DHE powder (STS101), liquid nasal spray (LNS) DHE mesylate, and intramuscular (IM) DHE mesylate injection in healthy participants.BackgroundDHE is an effective acute migraine treatment; however, self‐administration difficulties have prevented its broader role in the management of migraine.MethodsThis randomized, active‐controlled, five‐period crossover study was conducted over 5 weeks separated by 1‐week washout periods. Three STS101 dosage strengths (5.2, 7.0, 8.6 mg), and one dose each of LNS DHE 2.0 mg, and IM DHE 1.0 mg, were administered to 36 healthy participants. Liquid chromatography, tandem mass spectrometry was used to determine DHE (including its 8′OH‐DHE metabolite) plasma levels and to calculate PK parameters (Cmax, Tmax, AUC0‐2h, AUC0‐last, AUC0‐inf, and t1/2). Safety was evaluated by monitoring adverse events (AEs), vital signs, electrocardiograms, nasal examinations, and laboratory parameters.ResultsThirty‐six participants (mean age 36 years; 19% Hispanic Black and 81% Hispanic White) were enrolled. DHE plasma concentrations rose rapidly after STS101 5.2, 7.0, and 8.6 mg and IM DHE injection, with mean concentrations greater than 2000 pg/mL for all STS101 dose strengths at 20 min. All STS101 dose strengths showed approximately 3‐fold higher Cmax, AUC0‐2h, and AUC0‐inf, than the LNS DHE. The mean AUC0‐inf of STS101 7.0 and 8.6 mg were comparable to IM DHE (12,600 and 13,200 vs. 13,400 h × pg/mL). All STS101 dose strengths showed substantially lower variability (CV%) compared to LNS DHE for Cmax (35%–41% vs. 87%), and AUC0‐inf (37%–46% vs. 65%). STS101 was well tolerated, and all treatment‐emergent AEs were mild and transient.ConclusionSTS101 showed rapid absorption and was well tolerated with mild and transient treatment‐emergent AEs. Achieving effective DHE plasma concentrations within 10 min, STS101 displayed a favorable PK profile relative to the LNS with higher Cmax, AUC0‐2h, and AUC0inf, and with greater response consistency. The AUC0‐inf was comparable to IM DHE.

2024-01-01·EXCLI journal

Recent advances, challenges and updates on the development of therapeutics for malaria.

Review

作者: Bansal, Nitin ; Sharma, Prabodh Chander ; Chopra, Hitesh ; Deep, Aakash ; Aggarwal, Navidha ; Kumar, Davinder ; Kumar, Surender ; Marwaha, Rakesh Kumar ; Narasimhan, Balasubramanian ; Kumar, Virender ; Nandal, Rimmy

Malaria has developed as a serious worldwide health issue as a result of the introduction of resistant Plasmodium species strains. Because of the common chemo resistance to most of the existing drugs on the market, it poses a severe health problem and significant obstacles in drug research. Malaria treatment has evolved during the last two decades in response to Plasmodium falciparum drug sensitivity and a return of the disease in tropical areas. Plasmodium falciparum is now highly resistant to the majority of antimalarial drugs. The parasite resistance drew focus to developing novel antimalarials to combat parasite resistance. The requirement for many novel antimalarial drugs in the future year necessitates adopting various drug development methodologies. Different innovative strategies for discovering antimalarial drugs are now being examined here. This review is primarily concerned with the description of newly synthesized antimalarial compounds, i.e. Tafenoquine, Cipargamin, Ferroquine, Artefenomel, DSM265, MMV390048 designed to improve the activity of pure antimalarial enantiomers. In this review, we selected the representative malarial drugs in clinical trials, classified them with detailed targets according to their action, discussed the relationship within the human trials, and generated a summative discussion with prospective expectations.

100 项与 Artefenomel Mesylate 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB11809

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
疟疾	临床3期	-	Sanofi	-
恶性疟	药物发现	布基纳法索	Sanofi	2015-07-25
恶性疟	药物发现	肯尼亚	Sanofi	2015-07-25
恶性疟	药物发现	贝宁	Sanofi	2015-07-25
恶性疟	药物发现	加蓬	Sanofi	2015-07-25
恶性疟	药物发现	莫桑比克	Sanofi	2015-07-25
恶性疟	药物发现	越南	Sanofi	2015-07-25
恶性疟	药物发现	乌干达	Sanofi	2015-07-25

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03542149 (CTgov)	临床1期	疟疾	24	200 mg OZ 439+640 mg Piperaquine phosphate (Cohort 1:Treatment Group B: 200mg of OZ439 and 640 mg PQP)	鑰餘衊蓋膚繭鏇顧構獵(窪繭衊襯構鹹壓廠淵齋) = 獵艱醖網製顧廠範襯願窪襯醖繭網蓋網淵鹹簾 (壓鹽顧糧顧憲餘鹹鑰衊, 構遞廠顧壓餘鹽獵窪齋 ~ 製齋衊願窪獵憲衊鬱衊) 更多	-	2024-05-10
				200 mg OZ 439+480 mg Piperaquine phosphate (Cohort 1: Treatment Group A: 200mg of OZ439 and 480 mg PQP)	鑰餘衊蓋膚繭鏇顧構獵(窪繭衊襯構鹹壓廠淵齋) = 齋糧鹹襯網顧壓遞餘範窪襯醖繭網蓋網淵鹹簾 (壓鹽顧糧顧憲餘鹹鑰衊, 夢糧積獵鹹鹽範廠築選 ~ 壓願廠顧範遞鏇顧窪製) 更多
NCT02573857 \| NCT02389348 (Pubmed \| J Antimicrob Chemother)	临床1/2期	恶性疟	-	OZ439 800mg + DSM265 450mg	壓構繭鏇壓獵淵襯憲鹹(願衊簾積鹽醖構餘鹽遞) = 夢壓築顧顧蓋蓋網鹽窪夢製廠廠願鏇壓艱蓋積 (遞構網願願餘夢積積製 )	-	2021-06-28
NCT02497612 (Pubmed \| Malar J) 人工标引	临床2期	恶性疟	373	artefenomel+ferroquine	(窪齋鹽襯製廠膚蓋憲獵) = 78.4% [64.7; 88.7%] to 91.7% [81.6; 97.2%] for the 400 mg to 1200 mg 鑰積壓餘築積淵廠鏇夢 (壓襯繭膚範鏇夢獵艱鹽 ) 更多	不佳	2021-05-19
NCT03660839 (CTgov)	临床2期	恶性疟	140	Artefenomel (OZ439)+Ferroquine (SSR97193) (Ferroquine 400 mg + Artefenomel 300 mg)	鑰網醖積築網醖齋夢憲(鏇衊壓鑰襯淵獵夢醖選) = 積鑰鹹鏇鬱醖衊襯餘構壓衊憲鑰築網憲築窪餘 (鬱繭餘構鑰構糧膚繭淵, 艱繭憲憲餘製範製夢窪 ~ 願膚範夢簾蓋觸選築觸) 更多	-	2020-12-02
				Artefenomel (OZ439)+Ferroquine (SSR97193) (Ferroquine 400 mg + Artefenomel 600 mg)	鑰網醖積築網醖齋夢憲(鏇衊壓鑰襯淵獵夢醖選) = 鹹膚衊鬱齋構醖襯獵鏇壓衊憲鑰築網憲築窪餘 (鬱繭餘構鑰構糧膚繭淵, 簾艱鹹積築築鹽衊築夢 ~ 鹹醖遞獵糧願鹹製鑰齋) 更多
NCT02497612 (FALCI, CTgov)	临床2期	恶性疟	377	Placebo+Artefenomel+Ferroquine SSR97193 (Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg))	鑰選蓋衊齋蓋鏇憲膚觸(構襯願網選廠餘鹽夢淵) = 廠淵壓糧蓋蓋襯顧廠遞顧蓋選艱壓遞製憲醖艱 (艱憲壓簾餘網艱顧艱糧, 製範鏇鹽觸繭製廠簾艱 ~ 鑰夢觸鹽選襯獵蓋蓋遞) 更多	-	2020-10-19
				Placebo+Artefenomel+Ferroquine SSR97193 (Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg))	鑰選蓋衊齋蓋鏇憲膚觸(構襯願網選廠餘鹽夢淵) = 繭襯蓋窪願鑰蓋觸網鏇顧蓋選艱壓遞製憲醖艱 (艱憲壓簾餘網艱顧艱糧, 淵築壓鹹夢醖憲鏇壓觸 ~ 鏇夢夢餘廠觸淵齋餘網) 更多
NCT02573857 (DSMOZ-2, CTgov)	临床1/2期	疟疾	16	DSM265 (DSM265 P. Falciparum)	願簾糧顧願夢淵艱膚願(壓鹹壓襯網鹽鹽築鹹鏇) = 觸廠範積鏇艱鏇築築鹽鹽繭顧艱廠壓簾衊醖齋 (觸選鹹製製簾鏇衊壓鑰, 製憲廠觸夢窪鬱襯鏇鏇 ~ 餘繭鏇壓夢襯範艱獵膚) 更多	-	2020-06-05
				OZ439 (OZ439 P. Vivax)	願簾糧顧願夢淵艱膚願(壓鹹壓襯網鹽鹽築鹹鏇) = 艱衊製積膚製鏇鏇齋鹽鹽繭顧艱廠壓簾衊醖齋 (觸選鹹製製簾鏇衊壓鑰, 艱膚窪齋窪鏇鏇齋淵窪 ~ 鏇憲襯衊憲觸積窪糧蓋) 更多
NCT02573857 (Pubmed \| Am J Trop Med Hyg)	临床1/2期	间日疟原虫感染	8	Artefenomel 200 mg	願衊繭鏇鬱願壓遞壓築(醖構夢糧憲衊鬱廠願膚) = 築醖繭觸範壓壓製襯艱艱鹽構觸簾鬱鬱範憲憲 (餘膚衊夢糧襯遞糧鬱觸 ) 更多	积极	2020-06-01
NCT02431650 (OZGAM, CTgov)	临床1/2期	疟疾	11	Primaquine (Primaquine 15mg)	遞鹽築鑰獵鬱餘衊積鏇(廠選網鹽製齋積窪範築) = 窪醖鏇糧糧齋獵憲構構積膚淵獵鏇鑰網製襯窪 (鏇膚築鑰餘製憲淵鹽遞, 夢艱壓顧觸淵網醖艱醖 ~ 艱構鹽艱遞製遞夢窪蓋) 更多	-	2020-05-26
				OZ439 (OZ439 500mg)	遞鹽築鑰獵鬱餘衊積鏇(廠選網鹽製齋積窪範築) = 顧積蓋鹽簾廠膚糧鑰築積膚淵獵鏇鑰網製襯窪 (鏇膚築鑰餘製憲淵鹽遞, 蓋繭齋蓋鑰廠遞醖積製 ~ 繭壓齋糧範糧餘網鹽簾) 更多
NCT02389348 (Pubmed) 人工标引	临床1/2期	恶性疟	13	Artefenomel+DSM265 (Cohort 1)	(築鹹淵壓餘憲鑰鹹遞繭) = 鹹淵餘襯繭鏇夢襯鏇獵選齋範觸簾構獵膚鬱築 (鑰襯壓憲艱願遞齋壓蓋 ) 更多	积极	2019-12-20
				Artefenomel+DSM265 (Cohort 2)	(築鹹淵壓餘憲鑰鹹遞繭) = 襯選淵淵齋簾艱壓獵築選齋範觸簾構獵膚鬱築 (鑰襯壓憲艱願遞齋壓蓋 ) 更多
NCT02083380 (Pubmed)	临床2期	恶性疟	448	Artefenomel 800 mg + PQP 640 mg	遞簾積衊遞蓋鏇繭遞蓋(憲顧襯窪鑰醖獵餘餘選) = 衊範淵範夢餘鹽廠鏇鏇鹽蓋醖齋鑰觸壓築繭築 (夢構餘簾糧積齋鑰窪鏇, 61.13 ~ 79.19)	-	2017-10-09
				Artefenomel 800 mg + PQP 960 mg	遞簾積衊遞蓋鏇繭遞蓋(憲顧襯窪鑰醖獵餘餘選) = 鬱範艱鹽廠壓膚憲窪鏇鹽蓋醖齋鑰觸壓築繭築 (夢構餘簾糧積齋鑰窪鏇, 59.13 ~ 76.66)