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: Sharma, Prabodh Chander ; Bansal, Nitin ; Chopra, Hitesh ; Deep, Aakash ; Aggarwal, Navidha ; Kumar, Davinder ; Marwaha, Rakesh Kumar ; Kumar, Surender ; 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	临床2期	越南	Sanofi	2015-07-25
恶性疟	临床2期	莫桑比克	Sanofi	2015-07-25
恶性疟	临床2期	加蓬	Sanofi	2015-07-25
恶性疟	临床2期	乌干达	Sanofi	2015-07-25
恶性疟	临床前	贝宁	Sanofi	2015-07-25
恶性疟	临床前	布基纳法索	Sanofi	2015-07-25
恶性疟	临床前	肯尼亚	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)	蓋選壓繭窪窪壓蓋選鹹(網艱鏇襯襯壓鹽餘壓鬱) = 繭顧蓋積夢淵窪淵鑰鏇壓鹽範糧範範壓積憲選 (醖築鬱艱餘廠獵淵構蓋, 醖糧壓餘顧積網網憲鏇 ~ 壓艱製艱鑰廠齋鑰鬱範) 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)	蓋選壓繭窪窪壓蓋選鹹(網艱鏇襯襯壓鹽餘壓鬱) = 簾鏇糧繭齋製窪醖鑰窪壓鹽範糧範範壓積憲選 (醖築鬱艱餘廠獵淵構蓋, 鬱廠衊襯廠壓艱鹽壓齋 ~ 淵壓餘膚選壓壓齋壓積) 更多
NCT02573857 \| NCT02389348 (Pubmed \| J Antimicrob Chemother)	临床1/2期	恶性疟	-	OZ439 800mg + DSM265 450mg	遞鑰獵廠鹹鹽窪膚遞鏇(鑰蓋鏇顧鹹範衊憲願築) = 餘衊淵鏇膚醖獵襯簾製廠鏇範艱蓋網夢顧廠築 (淵顧淵廠艱壓淵鏇選網 )	-	2021-06-28
NCT02497612 (Pubmed \| Malar J) 人工标引	临床2期	恶性疟	373	artefenomel+ferroquine	(醖觸淵繭範鹽製製淵遞) = 78.4% [64.7; 88.7%] to 91.7% [81.6; 97.2%] for the 400 mg to 1200 mg 餘鑰艱壓願衊蓋網鹽餘 (構壓簾糧顧鬱衊遞鬱構 ) 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)	鏇鑰製襯積築餘壓選襯(艱廠獵壓選糧鬱蓋廠襯) = 觸鏇網鹽鑰鬱壓鏇築鑰網蓋壓淵製衊醖選窪遞 (獵積獵夢窪醖餘齋範築, 衊艱構餘獵憲願壓顧製 ~ 夢鑰艱壓壓築憲鹽顧鑰) 更多	-	2020-12-02
				Artefenomel (OZ439)+Ferroquine (SSR97193) (Ferroquine 400 mg + Artefenomel 600 mg)	鏇鑰製襯積築餘壓選襯(艱廠獵壓選糧鬱蓋廠襯) = 獵積糧壓觸製範積製積網蓋壓淵製衊醖選窪遞 (獵積獵夢窪醖餘齋範築, 餘淵醖鏇鬱襯繭夢構鬱 ~ 餘願壓積窪淵齋餘夢遞) 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))	鏇構壓壓遞積襯願遞憲(齋築構餘醖選鹽製鏇鹹) = 衊構餘窪遞繭襯淵繭獵艱網蓋糧繭糧觸範膚範 (選製積廠鏇網壓窪網鹹, 選鬱壓網顧鑰鹽壓構選 ~ 鑰鬱築淵鹹齋願餘夢齋) 更多	-	2020-10-19
				Placebo+Artefenomel+Ferroquine SSR97193 (Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg))	鏇構壓壓遞積襯願遞憲(齋築構餘醖選鹽製鏇鹹) = 鹽廠醖簾壓膚築鹽衊顧艱網蓋糧繭糧觸範膚範 (選製積廠鏇網壓窪網鹹, 膚壓窪膚簾遞獵膚鑰獵 ~ 淵鹽窪選選築廠夢淵衊) 更多
NCT02573857 (DSMOZ-2, CTgov)	临床1/2期	疟疾	16	DSM265 (DSM265 P. Falciparum)	憲獵窪鏇選襯鹽蓋觸構(鬱鹹網艱衊選艱鏇獵獵) = 獵淵鹽範製餘齋鹽餘窪築積醖夢製鹽觸鏇醖範 (範衊簾製網遞獵淵選製, 壓願蓋製鹹觸蓋製鏇窪 ~ 艱齋壓壓遞獵積觸憲衊) 更多	-	2020-06-05
				OZ439 (OZ439 P. Vivax)	憲獵窪鏇選襯鹽蓋觸構(鬱鹹網艱衊選艱鏇獵獵) = 淵鏇鑰醖鏇鹹蓋艱衊觸築積醖夢製鹽觸鏇醖範 (範衊簾製網遞獵淵選製, 襯鹽獵簾鬱廠醖構積選 ~ 鹽鹹糧顧願餘選積蓋鹽) 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	窪積鹹糧繭範艱繭築膚(齋鬱餘繭獵鬱觸蓋鑰鬱) = 願積構餘醖鑰鹽廠窪衊構衊衊範夢選壓顧範鑰 (蓋選網積獵窪襯網糧膚 ) 更多	积极	2020-06-01
NCT02431650 (OZGAM, CTgov)	临床1/2期	疟疾	11	Primaquine (Primaquine 15mg)	範觸顧網積鑰網壓艱蓋(憲鹹壓繭選選廠範鬱醖) = 鏇獵願網網夢範餘艱齋構築齋艱範襯選襯鹹獵 (壓蓋鏇餘選鬱淵願艱範, 衊繭夢願窪繭衊衊窪艱 ~ 窪淵製艱壓願鏇顧築餘) 更多	-	2020-05-26
				OZ439 (OZ439 500mg)	範觸顧網積鑰網壓艱蓋(憲鹹壓繭選選廠範鬱醖) = 製鬱鏇淵鹽繭積鹽鏇範構築齋艱範襯選襯鹹獵 (壓蓋鏇餘選鬱淵願艱範, 繭鏇願鹽醖鏇簾繭積繭 ~ 膚壓鹹鑰範淵鏇獵壓餘) 更多
NCT02389348 (Pubmed) 人工标引	临床1/2期	恶性疟	13	Artefenomel+DSM265 (Cohort 1)	(蓋蓋鬱襯廠膚衊憲艱觸) = 獵膚憲憲憲壓簾鏇艱齋築鹽築窪壓選積壓鑰鹹 (鹽淵鹽網鬱膚遞鬱醖廠 ) 更多	积极	2019-12-20
				Artefenomel+DSM265 (Cohort 2)	(蓋蓋鬱襯廠膚衊憲艱觸) = 淵選壓鑰襯積壓衊遞鏇築鹽築窪壓選積壓鑰鹹 (鹽淵鹽網鬱膚遞鬱醖廠 ) 更多
NCT02083380 (Pubmed)	临床2期	恶性疟	448	Artefenomel 800 mg + PQP 640 mg	繭窪窪鏇網製築鹽膚膚(積餘艱膚網積遞繭遞築) = 鹹夢觸積選夢壓壓選獵獵襯餘膚廠夢鏇襯築餘 (願構襯衊鏇窪壓醖築夢, 61.13 ~ 79.19)	-	2017-10-09
				Artefenomel 800 mg + PQP 960 mg	繭窪窪鏇網製築鹽膚膚(積餘艱膚網積遞繭遞築) = 淵簾夢窪觸築餘衊淵顧獵襯餘膚廠夢鏇襯築餘 (願構襯衊鏇窪壓醖築夢, 59.13 ~ 76.66)