预约演示
更新于：2026-10-23
Pavinetant
更新于：2026-10-23
概要
基本信息
原研机构 |
在研机构- |
最高研发阶段终止临床2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/序列
分子式C26H25N3O3S |
InChIKeyQYTBBBAHNIWFOD-NRFANRHFSA-N |
CAS号941690-55-7 |
关联
7
项与 Pavinetant 相关的临床试验NCT02865915
A Double-blind, Randomized, Parallel-group, Placebo-controlled Study of MLE4901 for the Treatment of Polycystic Ovary Syndrome (PCOS)
NCT02668185
Neurokinin 3 Receptor Antagonism as a Novel Treatment for Menopausal Hot Flushes
EUCTR2015-001553-32-GB
Neurokinin 3 Receptor Antagonism as a Novel Treatment for Menopausal Hot Flushes
100 项与 Pavinetant 相关的临床结果
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100 项与 Pavinetant 相关的转化医学
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100 项与 Pavinetant 相关的专利（医药）
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16
项与 Pavinetant 相关的文献（医药）2026-08-01DRUG SAFETY
Liver Safety of the Dual Neurokinin-1/-3 Receptor Antagonist Elinzanetant
Review
作者: Andrade, Raúl J ; Larrey, Dominique ; Trajanovic, Mila ; Horsmans, Yves ; Anderson, Richard A ; Zuurman, Lineke ; Groettrup-Wolfers, Esther ; Lewis, James H
BACKGROUND:
Elinzanetant is a selective dual neurokinin (NK)-1/-3 receptor antagonist for the treatment of moderate-to-severe vasomotor symptoms associated with menopause or caused by endocrine therapy. Elinzanetant has been approved by health authorities in several countries. The occurrence of elevated liver enzymes has been observed in clinical use with NK-3 receptor antagonists, e.g., fezolinetant and pavinetant, with recommendations for liver monitoring in the fezolinetant labeling information. Therefore, a thorough evaluation of the liver safety data from clinical trials with elinzanetant was undertaken.
OBJECTIVE:
To summarize available hepatic safety data from the clinical development program of elinzanetant.
METHODS:
The potential risk of drug-induced liver injury (DILI) associated with elinzanetant was evaluated on the basis of the analysis of 24 phase 1 studies, three phase 2 studies (RELENT-1, SWITCH-1, NIRVANA), and four randomized, placebo-controlled phase 3 studies (OASIS 1‒4). Liver safety assessments were conducted throughout the studies as per protocol. In the phase 3 studies, a liver safety monitoring board (LSMB) performed an independent and blinded review of cases meeting close liver observation criteria, in alignment with US Food and Drug Administration DILI Guidance and the Council for International Organizations of Medical Sciences 2020 consensus on DILI. An independent data and safety monitoring board monitored the general safety of the participants.
RESULTS:
In the clinical program (phases 1‒3), there was no imbalance between the elinzanetant and placebo groups in alanine aminotransferase (ALT) elevations up to 5×, 10×, or 20× the upper limit of normal (ULN). In the pooled studies that included postmenopausal women, during weeks 1‒52 of treatment, ALT or aspartate transaminase (AST) elevations ≥ 3× ULN were observed in 1.2% of participants treated with elinzanetant 120 mg and in 1.0% of participants treated with placebo. In addition, there were no cases meeting Hy's law, and no indication of cholestatic injury. The LSMB assessed two cases on elinzanetant (2 out of 1697 participants, 0.12%) and one case on placebo (1 out of 1028, 0.10%) as probably related to study drug. For the cases on elinzanetant, one participant had a peak ALT level 7.4× ULN and the other had a peak ALT 3.5× ULN. Alkaline phosphatase and total bilirubin levels remained within reference range; both cases were mild and reversible. The peak ALT for the participant on placebo was 3.6× ULN. No case was classified as highly likely or definite.
CONCLUSIONS:
The aggregated phase 1‒3 clinical data, supported by preclinical toxicology and individual case adjudications of participants with elevated liver enzymes, suggest that there is a low risk of liver toxicity for elinzanetant. On the basis of these data, liver test monitoring was considered unnecessary in clinical practice by the LSMB (video abstract available online). Supplementary file2 (MP4 73923 KB).
2025-07-04CLIMACTERIC
NK3 receptor antagonist alters the centrally controlled perception of menopausal flushing – a pilot study
Article
作者: Skorupskaite, Karolina ; Anderson, Richard A. ; McLean, John ; Lumsden, Mary Ann ; Sassarini, Jenifer
OBJECTIVE:
Kisspeptin/neurokinin/dynorphin (KNDy) signaling links reproductive and thermoregulatory systems, and improvements in menopausal flushing are reported with neurokinin 3 receptor (NK3R) antagonists. A rise in brainstem activity preceding a flush has been proposed as its functional origin, with subsequent activity in the insula and prefrontal cortices reflecting individual perception. Using functional magnetic resonance imaging (fMRI), this study investigated the central effect of the NK3R antagonist MLE4901 during a flush, particularly functional connectivity changes in the salience network.
METHOD:
Five postmenopausal women with flushes completed a 1-week flush diary prior to baseline fMRI, during which hot flushes were triggered by heating. Diaries were continued during 7 days of treatment with the NK3R antagonist MLE4901, with repeat fMRI on day 7. Sternal monitors recorded objective flushing before each fMRI. Connectivity changes in the salience network post flush were assessed.
RESULTS:
Treatment with MLE4901 reduced the subjective flush frequency (from median 6.9 to 1.1 per day; p = 0.02) without changes in objective flushes. Treatment decreased right anterior insula connectivity, which correlated significantly with decreased subjective flushing.
CONCLUSION:
This pilot study demonstrates decreased connectivity in the salience network during NK3R antagonist treatment. This may indicate areas of interest for further targeted fMRI studies and mechanistic investigation of this novel treatment for flushing.
2025-06-01BRAIN RESEARCH
In silico screening to search for selective sodium channel blockers: When size matters
Article
作者: Gavernet, Luciana ; Orsi, Federico ; Fallico, Maximiliano José ; Enrique, Nicolás ; Prada Gori, Denis Nihuel ; Talevi, Alan ; Alberca, Lucas Nicolás ; Martín, Pedro
Dravet Syndrome is a severe childhood drug-resistant epilepsy. The predominant etiology of this condition is related to de novo mutations within the SCN1A gene, which codes for the alpha subunit of the NaV1.1 sodium channels. This dysfunction leads to hypoexcitability of GABAergic interneurons. In turn, the loss of electrical excitability in GABAergic interneurons leads to an imbalance of excitation over inhibition in many neural circuits. Notably, exacerbation of symptoms is observed when non-selective sodium channel blockers are administered to patients with Dravet. Recent studies in animal models of Dravet have highlighted the potential of highly specific sodium channel blockers capable of blocking other sodium channel subtypes without inhibiting NaV1.1 current and selective activators of NaV1.1 as viable therapeutic strategies for alleviating Dravet Syndrome symptoms. Here, we describe the development and validation of ligand-based machine learning models to identify ligands with inhibitory effects on sodium channel isoforms NaV1.1 and NaV1.2. These models were built based on in-house open-source routines and Mordred molecular descriptors. First, linear classifiers were inferred using a combination of feature-bagging and Forward Stepwise selection. Secondly, ensemble learning was applied to build meta-classifiers with improved predictive ability, whose performance was tested in retrospective screening experiments. After in silico validation, the models were applied to screen for drug repurposing opportunities in the DrugBank and Drug Repurposing Hub databases, to identify selective blocking agents of NaV1.2 devoid of NaV1.1 blocking activity, as potential compounds for the treatment of Dravet Syndrome. Forty in silico hits were later identified in a prospective screening experiment. Four of them were acquired and submitted to experimental confirmation via patch clamp: three of these candidates, Eltrombopag, Sufugolix, and Glesatinib, showed blocking effects on NaV1.2 currents, although no subtype selectivity was observed. The different predictive abilities of the NaV1.1 and NaV1.2 models may be attributed to the different sizes of the datasets used to train and validate the respective models.
100 项与 Pavinetant 相关的药物交易
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外链
| KEGG | Wiki | ATC | Drug Bank |
|---|---|---|---|
| D11345 | Pavinetant | - |
研发状态
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 |
|---|---|---|---|---|
| 多内分泌代谢卵巢综合征 | 临床2期 | 美国 | 2013-06-01 | |
| 多内分泌代谢卵巢综合征 | 临床2期 | 德国 | 2013-06-01 | |
| 多内分泌代谢卵巢综合征 | 临床2期 | 英国 | 2013-06-01 | |
| 精神分裂症 | 临床2期 | 美国 | 2008-05-01 |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
临床2期 | 37 | Placebo | 廠膚鑰餘廠齋繭鬱製顧(鏇觸構窪網願憲廠壓艱) = 壓鹽網艱選獵鹽範獵願 廠構選製製顧願衊製簾 (願簾衊製網顧願鹽積願, 餘遞窪製壓艱願醖鹹鑰 ~ 築齋憲蓋繭鑰糧製淵鬱) 更多 | - | 2021-05-03 | ||
临床2期 | 55 | Placebo (Placebo Treatment Arm) | 構齋夢顧製蓋選製廠淵(憲遞範餘憲製製獵衊簾) = 製築蓋願顧鬱鹹艱餘糧 襯衊憲鏇觸簾餘鹹選選 (鏇顧鏇獵願築鏇壓積願, 觸願顧鏇遞積糧網糧製 ~ 齋夢夢襯構糧蓋鬱觸鏇) 更多 | - | 2020-06-16 | ||
(MLE4901 Treatment Arm) | 構齋夢顧製蓋選製廠淵(憲遞範餘憲製製獵衊簾) = 廠選糧衊鬱簾艱願繭顧 襯衊憲鏇觸簾餘鹹選選 (鏇顧鏇獵願築鏇壓積願, 齋壓糧艱繭顧繭獵積齋 ~ 齋衊鑰積鬱願製憲鑰鹽) 更多 | ||||||
临床2期 | 28 | NK3R antagonist (MLE4901) | 糧遞顧鬱顧構繭網蓋選(積醖築夢齋鹹積願製顧) = 醖網鏇膚獵獵廠膚淵築 繭觸顧製願獵窪窪襯顧 (顧壓夢夢齋鹽衊餘積觸 ) | 积极 | 2020-02-01 | ||
Placebo | 糧遞顧鬱顧構繭網蓋選(積醖築夢齋鹹積願製顧) = 廠鬱壓簾衊夢蓋艱襯窪 繭觸顧製願獵窪窪襯顧 (顧壓夢夢齋鹽衊餘積觸 ) | ||||||
临床2期 | 37 | 艱壓憲鹽觸糧壓範淵膚(醖窪鹹製願齋製簾淵繭) = 簾簾夢獵築憲製製糧膚 範窪鹹廠憲齋淵鹽襯糧 (夢餘選獵膚淵衊網鏇構, 15.99 ~ 23.42) | 积极 | 2017-05-06 | |||
Placebo | 艱壓憲鹽觸糧壓範淵膚(醖窪鹹製願齋製簾淵繭) = 糧廠襯製醖鹽鑰齋艱廠 範窪鹹廠憲齋淵鹽襯糧 (夢餘選獵膚淵衊網鏇構, 40.81 ~ 58.56) | ||||||
临床2期 | 67 | 願鬱獵製網衊鹽鏇鹽廠(糧積製鏇構襯積網遞顧) = 構衊憲製製鹹夢膚憲鏇 醖製製壓繭壓鑰艱選膚 (構鬱餘蓋選糧夢繭艱壓 ) | 积极 | 2016-11-01 | |||
Placebo | - | ||||||
临床2期 | 67 | placebo (Placebo) | 蓋壓襯鹽壓艱蓋醖鏇鏇(壓齋遞憲繭願製獵窪壓) = 壓築獵鬱積夢鑰繭簾膚 壓遞淵窪獵選鹹鹽願鹽 (廠製窪積鑰鑰遞艱醖遞, 夢簾鹽窪鹹鬱簾遞憲網 ~ 遞獵願鏇構壓窪築築鑰) 更多 | - | 2015-10-12 | ||
AZD4901 (20 mg AZD4901 qd) | 蓋壓襯鹽壓艱蓋醖鏇鏇(壓齋遞憲繭願製獵窪壓) = 鬱憲醖觸觸淵築壓襯觸 壓遞淵窪獵選鹹鹽願鹽 (廠製窪積鑰鑰遞艱醖遞, 鏇網鏇餘衊鬱鹹顧鬱網 ~ 廠願簾蓋顧壓積窪憲顧) | ||||||
临床2期 | 106 | (AZD2624) | 衊窪淵艱艱繭餘鹽醖繭(齋醖範鏇衊襯夢鏇範積) = 鑰遞餘憲繭蓋遞積觸選 觸範廠夢夢鹹繭觸築廠 (遞膚鏇範鏇襯夢顧鹽醖, 2.27) 更多 | - | 2011-06-23 | ||
Placebo (Placebo) | 衊窪淵艱艱繭餘鹽醖繭(齋醖範鏇衊襯夢鏇範積) = 鏇窪夢淵廠夢觸鏇願繭 觸範廠夢夢鹹繭觸築廠 (遞膚鏇範鏇襯夢顧鹽醖, 2.35) 更多 |
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