A Randomized, Double-blind, Placebo-controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of Repeated Dosing Regimens of AL-794 in Healthy Volunteers

The purpose of this study is to evaluate the safety and tolerability (including incidence of central nervous system [CNS] related events such as lightheadedness and dizziness), of multiple oral doses of AL-794 in healthy volunteers (HV). Also, to evaluate the pharmacokinetics of ALS-033719 and ALS-033927 in plasma after multiple oral doses of AL-794 in HV.

开始日期2018-03-03

申办/合作机构

Alios BioPharma, Inc.

NCT03126097

/ Terminated临床1期

A Phase 1, Open-label Study in Healthy Female Subjects to Investigate the Drug-drug Interaction Between JNJ-64155806 and Ethinylestradiol/Drospirenone

The primary purpose of this study is to evaluate the effect of single and multiple doses of JNJ-64155806 on the steady-state pharmacokinetics (PK) of ethinylestradiol and drospirenone and vice versa in healthy female participants.

开始日期2017-04-13

申办/合作机构

Janssen Research & Development LLC

NCT02888327

/ Completed临床1期

A Phase-1, Open-label, Four Group, Fixed-Sequence Study to Evaluate the Effect of AL-794 on the Pharmacokinetics of Oseltamivir, JNJ-63623872, and Probes for P-glycoprotein, CYP3A and OATP1B1 in Healthy Volunteers

This open-label, four group, fixed-sequence study will evaluate the safety and pharmacokinetic interaction of AL-794 on oseltamivir, JNJ-63623872 (formerly VX-787) and probes for P-glycoprotein, CYP3A and OATP1B1 in healthy volunteers.

开始日期2016-07-31

申办/合作机构

Alios BioPharma, Inc.

100 项与 AL-794 相关的临床结果

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100 项与 AL-794 相关的转化医学

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100 项与 AL-794 相关的专利（医药）

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项与 AL-794 相关的文献（医药）

2019-09-01·Antiviral research2区 · 医学

Antivirals targeting the polymerase complex of influenza viruses

2区 · 医学

Review

作者: Hayden, Frederick G ; Hurt, Aeron C ; Mifsud, Edin J

Current influenza antivirals have limitations with regard to their effectiveness and the potential emergence of resistance. Encouragingly, several new compounds which inhibit the polymerase of influenza viruses have recently been shown to have enhanced pre-clinical and clinical effectiveness compared to the neuraminidase inhibitors, the mainstay of influenza antiviral therapy over the last two decades. In this review we focus on four compounds which inhibit polymerase function, baloxavir marboxil, favipiravir, pimodivir and AL-794 and discuss their clinical and virological effectiveness, their propensity to select for resistance and their potential for future combination therapy with the most commonly used neuraminidase inhibitor, oseltamivir.

2019-01-07·The Journal of infectious diseases2区 · 医学

Antiviral Activity, Safety, and Pharmacokinetics of AL-794, a Novel Oral Influenza Endonuclease Inhibitor: Results of an Influenza Human Challenge Study

2区 · 医学

Article

作者: Chanda, Sushmita ; Fry, John ; Jekle, C Andreas ; Mitchell, Toni ; Yogaratnam, Jeysen ; Kakuda, Thomas N ; Fennema, Hein ; Symons, Julian A ; Van Remoortere, Pieter ; Boyce, Malcolm ; Rito, Jennifer ; Balaratnam, Ganesh ; Sahgal, Omair ; Gupta, Kusum

Background:

AL-794 is an orally active prodrug of ALS-033719, which selectively inhibits the endonuclease domain of influenza virus A and B polymerase.

Methods:

In a phase 1, double-blinded, randomized, placebo-controlled study, healthy subjects were inoculated intranasally with influenza virus (A/Perth/16/2009 H3N2) after confirmation of infection or on day 4. Subjects received 50 mg of AL-794, 150 mg of AL-794, or placebo twice daily for 5 days. Viral load, influenza symptoms, pharmacokinetics, and safety were evaluated.

Results:

A total of 61 subjects were inoculated. In 42 infected subjects, the mean peak viral load for 50-mg AL-794 recipients, 150-mg AL-794 recipients, and placebo recipients was 3.54, 2.77, and 3.72 log10 50% tissue culture infectious doses (TCID50)/mL, respectively. The mean influenza viral load area under the curve in the corresponding treatment groups was 137, 87.5, and 142 log10 TCID50/mL·h, respectively, and the median time to virus nondetection was 117, 75.3, and 108 hours, respectively. AL-794 was well tolerated, and no viral resistance to ALS-033719 was identified.

Conclusion:

Following oral administration of AL-794, significant dose-dependent antiviral activity was noted, with a greater decrease in viral load, symptoms, and mucus weight at the 150-mg dose, compared with the 50-mg dose, and no safety concerns for either dose or placebo.

Clinical Trials Registration:

NCT02588521.

2018-10-01·Antiviral therapy4区 · 医学

Phase I Study on Safety and Pharmacokinetics of a Novel Influenza Endonuclease Inhibitor, AL-794 (JNJ-64155806), following Single- and Multiple-Ascending doses in Healthy Adults

4区 · 医学

Article

作者: Gupta, Kusum ; Rito, Jennifer ; Yogaratnam, Jeysen ; Chanda, Sushmita ; Remoortere, Pieter Van ; Mitchell, Toni ; Kakuda, Thomas N ; Symons, Julian A ; Fry, John ; Boyce, Malcolm

Background:

This double-blind, first-in-human Phase I study evaluated pharmacokinetics, safety and tolerability of AL-794 (prodrug of ALS-033719), a potent endonucle-ase inhibitor of influenza A and B in healthy volunteers.

Methods:

Healthy adult volunteers were randomized to AL-794 (50–2,000 mg single ascending doses, fasting) or placebo (5 cohorts, n=6:2 AL-794: placebo/cohort) in part 1, and AL-794 (50–600 mg multiple ascending doses, twice-daily, fed or fasted) or placebo (3 cohorts, n=8:2 AL-794: placebo/cohort) for 7 days in part 2. In part 3, 8 healthy volunteers from part 1 received 450 mg AL-794 ( n=6) or placebo ( n=2) following a high-fat meal. All dosing was done with an oral suspension. Blood and urine samples for pharmacokinetics were collected at scheduled times and analysed for ALS-033719 and ALS-033927 (inactive glucuronide) plasma concentrations using LC-MS/MS.

Results:

ALS-033719 plasma concentrations increased dose proportionately up to 150 mg but less than proportionately above 150 mg. Steady-state was generally achieved by the third dose. ALS-033719 exposure increased following administration with a standard meal (19%–33%) or high-fat meal (3–3.6-fold). ALS-033927 was the major metabolite observed. Renal elimination was negligible (0.2%). Seventeen AL-794-treated healthy volunteers reported ≥1 treatment-emergent adverse event (TEAE; part 1: n=6, 24%; part 2: n=11, 69%). The most common TEAEs were headache (part 1: n=3; part 2: n=5) and dizziness (part 1: n=2; part 2: n=6).

Conclusions:

AL-794 up to 200 mg twice daily achieved ALS-033719 exposures which are expected to be efficacious and were generally tolerated. Further studies are planned to characterize safety and antiviral activity.

项与 AL-794 相关的新闻（医药）

2023-03-08

·药闻康策

甲流之下，奥司他韦背后的药企

点击上方一键预约最新最热的医药健康新闻政策随着甲流来势汹汹，奥司他韦又火出圈，一度登上热搜。据了解，近一周来，天猫买药平台显示，搜索“奥司他韦”搜索用户数周环比上升了200%，其中奥司他韦儿童颗粒需求尤为旺盛，百度指数同样显示，近7天，“奥司他韦”和“甲流”这两个名词搜索量显著上升，整体日均值近万次，“甲流”这一关键词整体环比增长超4000%。奥司他韦背后的药企“卖断货”这个词特别亮眼，药企们自然得铆足干劲把“断层”补上。药品的充足储备跟大众健康息息相关，因此，奥司他韦背后的药企也因甲流的热度而备受关注。据药智数据统计，目前单奥司他韦申报厂家数高达71家，主要为胶囊、干混悬液、颗粒等剂型。除了原研药外，截至2月28日，通过一致性评价的厂家数34家，其中胶囊27家，干混悬剂7家。在药监局官网，奥司他韦已经获批的同类产品已有30款，涉及的药企有齐鲁制药、广东东阳光药业、四川科伦、南京海纳制药、华海药业等。如今奥司他韦虽然专利保护早就不再，市面上光是进入集采的仿制药就有10家，不乏石药、华海、齐鲁、科伦等国内一线化学药制剂大厂，然而东阳光药的市场地位依然难以撼动。光靠集采的那点量，制药大厂们基本都无心恋战。第七批集采约定的75mg奥司他韦胶囊共需1446万粒，即使按集采最高价、江苏诺泰奥塞诺公司报出的每一粒2.7元计算，这点采购量按比例分给10家药企，每家也就分到两三百万元的采购额。这些药企很难为了这点需求，贸然多筹备生产原料，去和东阳光药直接硬碰硬。种种原因叠加，导致奥司他韦虽已进入了国家集采，但供货主力依然只有东阳光药一家。过去十几年，东阳光药靠着奥司他韦这个品种名利双收。不过疫情三年，东阳光药也受损严重。2019年，东阳光药的奥司他韦颗粒、胶囊两个品种年销售加起来超过59亿元，占公司总收入的95%；但到了2021年，两个品种加起来也只有5.5亿元的销售额。东阳光药的业绩也随之剧烈波动。弯道超车，AI超声商业化进程提速在抗流感药物赛道，除了入局奥司他韦的药企们竞争激烈，其他品类的抗流感药物市场也扩增迅猛，布局的药企也不在少数，流感赛道竞争愈演愈烈。尽管Caption Health凭借FDA的认证率先做起了营收，但国内AI超声企业并未在商业化上落后太多距离。可以看到，除已经上市的几款抗流感药物外，众生药业研发的ZSP1273是国内首个完成II期临床试验的治疗甲型流感的小分子RNA聚合酶抑制剂，目前已经临床III期阶段；杨森制药的JNJ-5806是处于临床II期；Visterra的VIS410处于临床II期等。流感病毒是有周期的，每年都会爆发，每年也都会被压下来。面对流感病毒，我们早已认识到流感和其他所有的传染病一样。（来源:医药智投）药闻康策新媒体矩阵微信公众号点击下方一键关注【免责声明】1.“药闻康策”部分文章信息来源于网络转载是出于传递更多信息之目的，并不意味着赞同其观点或证实其内容的真实性。如对内容有疑议，请及时与我司联系。2.“药闻康策”致力于提供合理、准确、完整的资讯信息，但不保证信息的合理性、准确性和完整性，且不对因信息的不合理、不准确或遗漏导致的任何损失或损害承担责任。3.“药闻康策”所有信息仅供参考，不做任何商业交易或医疗服务的根据，如自行使用“药闻康策”内容发生偏差，我司不承担任何责任，包括但不限于法律责任，赔偿责任。欢迎转发分享、点赞、点在看

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100 项与 AL-794 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
流感病毒感染	临床1期	英国	Alios BioPharma, Inc.	2015-08-31

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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


NCT02588521 (Pubmed \| J Infect Dis)	临床1期	流感病毒感染	61	AL-794 50 mg	艱醖願齋繭選構鬱衊醖(築齋積夢構獵窪淵鹽範) = 衊壓範構夢膚鬱廠艱願遞鑰淵襯鑰構觸鏇鬱築 (製糧壓膚壓襯網窪艱鏇 ) 更多	-	2019-01-07
NCT02588521 (Pubmed \| J Infect Dis)	临床1期	流感病毒感染	61	AL-794 150 mg	艱醖願齋繭選構鬱衊醖(築齋積夢構獵窪淵鹽範) = 簾廠簾顧遞衊簾顧繭窪遞鑰淵襯鑰構觸鏇鬱築 (製糧壓膚壓襯網窪艱鏇 ) 更多	-	2019-01-07
NCT02588521 (Pubmed \| Antivir Ther)	临床1期	-	-	AL-794	壓衊醖積餘襯觸鑰願網(鬱憲壓簾憲艱觸願鏇餘) = increased following administration with a standard meal (19%-33%) or high-fat meal (3-3.6-fold) 餘鏇築製衊淵憲繭鏇齋 (糧醖醖鹽鏇醖淵醖願獵 ) 更多	-	2018-10-01