Efficacy and Safety of Edaravone Dexborneol Sublingual Tablet for Post-stroke Cognitive Impairment in Patients With Acute Ischemic Stroke: a Multicenter, Randomized, Double-blind, Placebo-controlled, Exploratory Phase II Clinical Trial.

This is a multicenter, randomized, double-blind, placebo-controlled, exploratory Phase II clinical trial.
The goal of this clinical trial is to assess the safety and efficacy of edaravone dexborneol sublingual tablets for post-stroke cognitive impairment in patients with acute ischemic stroke.
Participants will be required to receive 24 weeks treatment of edaravone dexborneol sublingual tablets or placebo during this study. The safety and efficacy endpoints will be compared in the patients with edaravone dexborneol sublingual tablets or placebo.

Start Date08 Apr 2024

Sponsor / Collaborator

Simcere Pharmaceutical Group Ltd.

CTR20240862 / RecruitingPhase 2

依达拉奉右莰醇舌下片使用对急性缺血性卒中后认知功能障碍的疗效和安全性：一项多中心、随机、双盲、安慰剂对照、探索性II期临床试验

[Translation] Efficacy and safety of edaravone-dexamethasone sublingual tablets for cognitive dysfunction after acute ischemic stroke: a multicenter, randomized, double-blind, placebo-controlled, exploratory phase II clinical trial

主要研究目的： 1.评估依达拉奉右莰醇舌下片治疗12周的安全性和耐受性 2.评估依达拉奉右莰醇舌下片治疗12周对缺血性卒中患者认知功能的影响次要研究目的： 1.评估依达拉奉右莰醇舌下片治疗12周对缺血性卒中患者卒中后认知功能障碍（PSCI）发生率的影响 2.评估依达拉奉右莰醇舌下片治疗12周对缺血性卒中患者认知功能评分的影响 3.评估依达拉奉右莰醇舌下片治疗12周对缺血性卒中患者各认知域（视空间和执行功能、命名、延迟回忆、注意力、语言、抽象、定向）评分的影响 4.评估依达拉奉右莰醇舌下片治疗4周、 12 周对缺血性卒中患者整体功能结局的影响

[Translation]

Main study objectives: 1. To evaluate the safety and tolerability of 12-week treatment with edaravone and dextrocarbol sublingual tablets 2. To evaluate the effect of 12-week treatment with edaravone and dextrocarbol sublingual tablets on cognitive function in patients with ischemic stroke Secondary study objectives: 1. To evaluate the effect of 12-week treatment with edaravone and dextrocarbol sublingual tablets on the incidence of post-stroke cognitive impairment (PSCI) in patients with ischemic stroke 2. To evaluate the effect of 12-week treatment with edaravone and dextrocarbol sublingual tablets on cognitive function scores in patients with ischemic stroke 3. To evaluate the effect of 12-week treatment with edaravone and dextrocarbol sublingual tablets on the scores of various cognitive domains (visuospatial and executive function, naming, delayed recall, attention, language, abstraction, orientation) in patients with ischemic stroke 4. To evaluate the effect of 4-week and 12-week treatment with edaravone and dextrocarbol sublingual tablets on the overall functional outcomes of patients with ischemic stroke

Start Date03 Apr 2024

Sponsor / Collaborator

Nanjing Simcere Dongyuan Pharmaceutical Co. Ltd.

ChiCTR2400086909 / RecruitingNot ApplicableIIT

Observation protocol for the efficacy of Edaravone Dexborneol in patients with acute ischemic stroke after alteplase therapy

Start Date01 Jan 2024

Sponsor / Collaborator-

100 Clinical Results associated with Edaravone/(+)-2-Decanol

100 Translational Medicine associated with Edaravone/(+)-2-Decanol

100 Patents (Medical) associated with Edaravone/(+)-2-Decanol

Literatures (Medical) associated with Edaravone/(+)-2-Decanol

23 Sep 2024·MOLECULAR BIOLOGY REPORTS

Potential of Edaravone Dexborneol in the treatment of cerebral ischemia: focus on cell death-related signaling pathways.

Review

Author: Nabavizadeh, Fatemeh ; Tamtaji, Omid Reza ; Rahmati-Dehkordi, Fatemeh ; Mirzaei, Hamed ; Aschner, Michael ; Dadgostar, Ehsan ; Zare-Hoseinabadi, Alireza ; Jafarpour, Hamed ; Khanifar, Hadi

Cerebral ischemia has the highest global rate of morbidity and mortality. It occurs when a sudden occlusion develops in the arterial system, and consequently some parts of the brain are deprived from glucose and oxygen due to the cessation of blood flow. The ensuing reperfusion of the ischemic area results in a cascade of pathological alternations like neuronal apoptosis by producing excessive reactive oxygen species (ROS), oxidative stress and neuroinflammation. Edaravone Dexborneol is a novel agent, comprised of Edaravone and Dexborneol in a 4:1 ratio. It has documented neuroprotective effects against cerebral ischemia injury. Edaravone Dexborneol improves neurobehavioral and sensorimotor function, cognitive function, brain edema, and blood-brain barrier (BBB) integrity in experimental models. It at dosages ranging between 0.375 and 15 mg/kg (from immediately after ischemia until the 28th post-ischemic days) has shown neuroprotective effects in experimental models of cerebral ischemia by inhibiting cell death-signaling pathways. For example, it inhibits apoptosis by increasing Bcl2, and reducing Bax and caspase-3 expression. Edaravone Dexborneol also inhibits pyroptosis by attenuating NF-κB/NLRP3/GSDMD signaling, as well as ferroptosis by activating the Nrf-2/HO-1/GPX4 signaling pathway. It also inhibits autophagy by targeting PI3K/Akt/mTOR signaling pathway. Here, we provide a review on the impacts of Edaravone Dexborneol on cerebral ischemia.

01 Sep 2024·NEUROPHARMACOLOGY

Edaravone Dexborneol ameliorates the cognitive deficits of APP/PS1 mice by inhibiting TLR4/MAPK signaling pathway via upregulating TREM2

Article

Author: Kang, Yunxiao ; Ji, Xiaoming ; Wang, Yu ; Wang, Jinyang ; Zhang, Tianyun ; Du, Longyuan ; Chu, Yun ; Shi, Geming ; Wang, Yue ; Zhang, Guoliang ; Liu, Junyan ; Cui, Rui

Currently, there are no effective therapeutic agents available to treat Alzheimer's disease (AD). However, edaravone dexborneol (EDB), a novel composite agent used to treat acute ischemic stroke, has recently been shown to exert efficacious neuroprotective effects. However, whether EDB can ameliorate cognitive deficits in AD currently remains unclear. To this end, we explored the effects of EDB on AD and its potential mechanisms using an AD animal model (male APP/PS1 mice) treated with EDB for 10 weeks starting at 6 months of age. Subsequent analyses revealed that EDB-treated APP/PS1 mice exhibited improved cognitive abilities compared to untreated APP/PS1 mice. Administration of EDB in APP/PS1 mice further alleviated neuropathological alterations of the hippocampus, including Aβ deposition, pyramidal cell karyopyknosis, and oxidative damage, and significantly decreased the levels of inflammatory cytokines (IL-1β, IL-6 and TNF-α) and COX-2 in the hippocampus of APP/PS1 mice. Transcriptome sequencing analysis demonstrated the critical role of the inflammatory reaction in EDB treatment in APP/PS1 mice, indicating that the alleviation of the inflammatory reaction by EDB in the hippocampus of APP/PS1 mice was linked to the action of the TREM2/TLR4/MAPK signaling pathway. Further in vitro investigations showed that EDB suppressed neuroinflammation in LPS-stimulated BV2 cells by inhibiting the TLR4/MAPK signaling pathway and upregulating TREM2 expression. Thus, the findings of the present study demonstrate that EDB is a promising therapeutic agent for AD-related cognitive dysfunction.

01 Sep 2024·Naunyn-Schmiedeberg's archives of pharmacology

Edaravone dexborneol promotes M2 microglia polarization against lipopolysaccharide-induced inflammation via suppressing TLR4/MyD88/NF-κB pathway

Article

Author: Hu, Xiaohui ; Li, Juanqin ; Huang, Jing ; Gong, Daokai

Edaravone dexborneol (ED) is a novel neuroprotective compound that consists of two active ingredients, edaravone and ( +)-borneol in a 4:1 ratio, which has been shown the anti-inflammatory properties in animal models of ischemic stroke, cerebral hemorrhage, and autoimmune encephalomyelitis. However, the effect of ED on the polarization of microglia in neuroinflammation has not been elucidated. This study was to investigate the effects of ED on the polarization of microglia induced by lipopolysaccharide (LPS) and potential mechanisms. BV-2 microglial cells were incubated with ED (100, 200, and 400 µM) for 2 h, followed by lipopolysaccharide (LPS, 1 µg/ml) for 12 h. The researchers used the Griess method, western blot, immunocytochemistry, and subcellular fractionation to assess the effects and potential mechanisms of ED on neuroinflammatory reactions. The expression of ROS and the activities of antioxidant enzymes (SOD, GPx, and CAT) in LPS-induced BV-2 cells were also measured using the DCFH-DA fluorescent probe and colorimetric methods, respectively. It was observed that ED significantly declined the levels of TLR4/NF-κB pathway-associated proteins (TLR4, MyD88, p65, p-p65, IκBα, p-IκBα, IKKβ, p-IKKβ) and therefore inhibited LPS-induced production of NO, IL-1β, and TNF-α. Moreover, ED markedly downregulated the M1 marker (iNOS) and upregulated the M2 marker (Arginase-1, Ym-1). In addition, ED also reduced ROS generation and enhanced GPx activity. ED induced the polarization of LPS-stimulated microglia from M1 to M2 against inflammation by negatively regulating the TLR4/MyD88/NF-κB signaling pathway. Additionally, ED performed antioxidative function by depleting the intracellular excessive ROS caused by LPS through the enhancement of the enzymatic activity of GPx. ED may be a potential agent to attenuate neuroinflammation via regulating the polarization of microglia.

News (Medical) associated with Edaravone/(+)-2-Decanol

05 Sep 2024

·www.prnewswire.com

Breakthrough Therapy designation for Sanbexin sublingual tablets granted by the United States Food and Drug Administration

NANJING, China, Sept. 5, 2024 /PRNewswire/ -- On September 2, 2024, Simcere Pharmaceuticals Group Ltd. (2096.HK) announced that Sanbexin Sublingual Tablets (Edaravone and Dexborneol sublingual tablets), an innovative drug for stroke, has been granted the Breakthrough Therapy designation by the U.S. Food and Drug Administration (FDA) for the treatment of Acute Ischemic Stroke (AIS). Sanbexin sublingual tablets is the first innovative drug in the world to be designated with the Breakthrough Therapy by the FDA for the treatment of stroke. The Breakthrough Therapy designation stems from the provisions of the "Food and Drug Administration Safety and Innovation Act". It is designed to expedite the development and regulatory review of drugs for treating serious diseases and addressing significant unmet medical needs. The designation will be beneficial for the drugs to obtain the FDA's guidance in the clinical development, accelerate the overseas clinical development process, and is also expected to significantly shorten the time for marketing review through the priority review designation. The Breakthrough Therapy designation is based on the significant improvement in efficacy metrics demonstrated by the sublingual tablets in a previous clinical study. The data from a multicenter, randomized, double-blind, parallel, placebo-controlled Phase III clinical study in China for the treatment of AIS demonstrated that Sanbexin sublingual tablets significantly improved neurological recovery and independent living ability in patients with AIS compared to placebo, meeting the expected efficacy endpoints with a favorable safety profile. JAMA Neurology published the study's key findings online. The designation will be beneficial for Simcere to obtain the FDA's guidance in the clinical development of Sanbexin sublingual tablets, accelerate the overseas clinical development process, and is also expected to significantly shorten the time for marketing review through the priority review designation. According to a recent article in The Lancet, stroke is the second leading cause of death and disability worldwide, with 12 million new cases and 6.6 million deaths each year. Among them, acute ischemic stroke is the most common type of stroke, accounting for about 70% of all strokes, and constituting a heavy disease burden for all countries around the world. The efficacy of acute ischemic stroke treatment is highly time-dependent. Receiving treatment as early as possible will help patients to improve their disease outcome and avoid disability. Sanbexin sublingual tablets is a brain cytoprotective agent composed of edaravone and dexborneol, two active ingredients with synergistic anti-oxidant and anti-inflammatory effects, which can significantly reduce brain cell injury or impairment caused by AIS. Such unique sublingual formulation can quickly disintegrate once in contact with the saliva once place under the tongue and can be absorbed into the blood through the sublingual venous plexus, which is expected to increase the flexibility of stroke treatment. Sequential therapy consisting of the marketed Sanbexin concentrated solution for Injection. These two formulae enable patients to receive a complete course of treatment in and outside of the hospital. On June 28, 2023, the new drug application (NDA) for Sanbexin sublingual tablets in China is accepted by the National Medical Products Administration. The first indication is for the improvement of neurological symptoms, daily activities, and functional impairment due to AIS. Phase I clinical trials for Sanbexin sublingual tablets on healthy volunteers have been completed in the United States.

Phase 3NDAPhase 1Priority ReviewBreakthrough Therapy

21 May 2024

·www.prnewswire.com

Simcere Phar-maceuticals Presented Six Studies on Sanbexin® at ESOC 2024

NANJING, China, May 21, 2024 /PRNewswire/ -- The 10th European Stroke Organization Congress (ESOC), held in Basel, Switzerland from May 15 to 17, 2024, showcased six studies on Sanbexin® (Edaravone and Dexborneol Concentrated Solution for Injection) and a new dosage form of sublingual tablets under development. These presentations brought new medical evidence on the mechanism of action and clinical application of Sanbexin® in treating stroke. Highlights Continue Reading Late-Breaking Abstract Oral Abstract Sanbexin®, the only Class 1 innovative drug approved worldwide since 2015, has been shown to reduce brain cell damage and dysfunction caused by ischemia and hypoxia in stroke patients. Its significance lies in its ability to combat the devastating effects of stroke, which is the second most common fatal disease globally and the first most common in China. The high recurrence rate, disability rate, and mortality rate associated with stroke place a heavy burden on society. In China, the incidence rate of ischemic stroke is the highest worldwide. Sanbexin® has been approved to address these challenges, offering new hope for patients and their families. Furthermore, the New Drug Application (NDA) for Sublingual Tablets of Sanbexin® has been accepted by the National Medical Products Administration (NMPA) on June 28, 2023. This development is expected to fill a critical gap in first-time and out-of-hospital drug delivery after stroke onset, increasing accessibility to the entire treatment course from hospital-based care to out-of-hospital care for patients. SOURCE Simcere

Drug ApprovalNDA

21 Feb 2024

·www.prnewswire.com

Findings of a Phase III Clinical Study of Sanbexin® Sublingual Tablets Published in JAMA

NANJING, China, Feb. 20, 2024 /PRNewswire/ -- On February 19, 2024, the Journal of American Medical Association•Neurology (JAMA NEUROLOGY, IF: 29.0) published online the key findings of a phase III clinical study (NCT04950920) (the "TASTE-SL Study") investigating Sanbexin® (a combination of edaravone and dexborneol) sublingual tablets for the treatment of acute ischemic stroke (the "AIS"). The findings indicate that Sanbexin® sublingual tablets has substantially enhanced neurological functions and independence in daily living activities among AIS patients following the treatment. Continue Reading JAMA-Neurology paper published online Feb.19 TASTE-SL study design TASTE-SL study primary end point Sanbexin® sublingual tablets is an innovative drug jointly developed by Simcere Pharmaceutical Group Ltd. ("Simcere") and Neurodawn Pharmaceutical Co., Ltd. ("Neurodawn"). The Sanbexin® sublingual tablets is expected to become a sequential therapy with Simcere's marketed Sanbexin® (Edaravone and Dexborneol Concentrated Solution for Injection) and allow patients to receive a complete course of treatment both in and outside of the hospital. On June 28, 2023, the New Drug Application (NDA) of the Sanbexin® sublingual tablets was accepted by the National Medical Products Administration of China (the "NMPA"). The first indication is for the improvement of neurological symptoms, activities of daily living, and functional disabilities caused by AIS. Sanbexin® sublingual tablet offers a novel approach to stroke treatment, leveraging the power of edaravone and dexborneol. The two active ingredients dissolve quickly under the tongue and are rapidly absorbed into the bloodstream via the sublingual venous plexus, providing unparalleled anti-inflammatory and free radical scavenging capabilities. By minimizing the cascading damage caused by AIS and protecting brain cells, this innovative formulation has the potential to expand treatment options and improve patient compliance. With its innovative sublingual delivery system, Sanbexin® is poised to revolutionize stroke care. The TASTE-SL study, published in JAMA Neurology, is a Phase III clinical trial that evaluated the safety and efficacy of Sanbexin® sublingual tablets in AIA patients. This multi-center, randomized, double-blind, placebo-controlled study enrolled 914 AIS patients within 48 hours of onset at 33 research sites in China from June 28, 2021, to August 10, 2022. Of these, 450 patients in the Sanbexin® sublingual tablets group received 36mg dose of sublingual edaravone dexborneol (edaravone 30mg, dexborneol 6mg) twice a day for 14 consecutive days), while 464 patients in the placebo group received a sublingual placebo (edaravone 0mg, dexborneol 60μg) twice a day for 14 consecutive days. The findings from the clinical trial suggest that the Sanbexin® sublingual tablets offer significant benefits for the treatment of AIS. The study, which included 302 patients, showed that those taking Sanbexin® sublingual tablets had a higher proportion of good functional outcomes (mRS score 0-1) on day 90 post-randomization compared to the placebo group: – 64.4% vs. 54.7%. The odds ratio was 1.50 (95% CI 1.15-1.95, p=0.003). Subgroup analyses of different demographic and clinical characteristics revealed consistent improvements in neurological function for the Sanbexin® sublingual tablet, regardless of age (≤65 or >65), gender, time from stroke onset to treatment (≤24 hours or >24 hours), presence of hypertension, hyperlipemia, diabetes, heart disease, or renal dysfunction. The Sanbexin® sublingual tablets demonstrated a favorable safety profile, with comparable rates of adverse events (AEs) and treatment-related AEs within 90 days between the two groups. This data strengthens Sanbexin® sublingual tablets' position as an effective and well-tolerated treatment option for AIS patients. Prof. Wang Yongjun, President of Beijing Tiantan Hospital of Capital Medical University, said, "In the field of stroke treatment, the continued exploration of brain cell protection therapy is beginning to show promise. Following the TASTE study, which validated the clinical benefit of edaravone dexamethasone injection, the TASTE-SL study further confirmed the efficacy and safety of the sublingual dosage form in the AIS population, and a more convenient way of administering the drug is expected to push the brain cell protection to home treatment." Prof. Fan Dongsheng from the Peking University Third Hospital said, "Sanbexin® sublingual tablets is effective in improving neurological function recovery and independent living ability of ischemic stroke patients after treatment and apply to a variety of treatment scenarios. This Phase III study of Sanbexin® sublingual tablet also provides a high-quality evidence-based basis for clinical brain cell protection, which provides a strong guarantee for stroke treatment." SOURCE Simcere Pharmaceutical Group Limited

Phase 3Clinical Result

100 Deals associated with Edaravone/(+)-2-Decanol

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	N07XX14	-

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Stroke	CN	Nanjing Simcere Dongyuan Pharmaceutical Co. Ltd.	29 Jul 2020

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Acute Ischemic Stroke	NDA/BLA	CN	2Y-Biopharma	29 Jun 2023
Acute Ischemic Stroke	NDA/BLA	CN	Simcere Pharmaceutical Group Ltd.	29 Jun 2023
Cognitive Dysfunction	Phase 2	CN	Nanjing Simcere Dongyuan Pharmaceutical Co. Ltd.	03 Apr 2024
Cerebral Hemorrhage	Phase 2	-	Jiangsu Simcere Pharmaceutical Co., Ltd.	01 Mar 2021
Brain Infarction	Phase 1	CN	Guangdong South China New Drug Creation Center	22 May 2019
Brain Infarction	Phase 1	CN	Nanjing Yoko Pharmaceutical Group Co. Ltd.	22 May 2019
Intracranial Hemorrhages	Phase 1	US	Yantai Yinuoyi Biomedical Technology Co., Ltd.	25 Oct 2018
Amyotrophic Lateral Sclerosis	IND Application	US	Nanjing Ningdan New Drug Technology Co., Ltd.	-
Cognition Disorders	IND Application	US	Nanjing Ningdan New Drug Technology Co., Ltd.	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04950920 (TASTE-SL, Literature) Manual	Phase 3	Acute Ischemic Stroke	914	Edaravone Dexborneol	imzwthpaoz(kwtmpdmhdu) = hesachkzqu kqvdtnnxyh (bsueipfqzg ) View more	Positive	19 Feb 2024
				Placebo	imzwthpaoz(kwtmpdmhdu) = tptyutirwh kqvdtnnxyh (bsueipfqzg ) View more
CTR20210233 (Corporate Publications) Manual	Phase 3	Acute Ischemic Stroke	-	先必新	hclmxenups(dwtrufbhpz) = 初步分析显示，相对于安慰剂，先必新舌下片显著改善AIS患者治疗后神经功能恢复及独立生活能力，达到预期疗效终点 pmwiytgszv (ehhssjanmr ) Met	Positive	01 Dec 2022
				Placebo
NEWS Manual	Not Applicable	Acute Ischemic Stroke	94	先必新	fqtxjznxzk(yukyqdqnfl) = peiufnctfx wdxecadqnd (whcmyqmiez, 4.11) View more	Positive	06 May 2022
				先必新+Alteplase	fqtxjznxzk(yukyqdqnfl) = qbeyupewam wdxecadqnd (whcmyqmiez, 2.15) View more
NCT02430350 (TASTE, Pubmed \| Cochrane Database Syst Rev) Manual	Phase 3	Acute Ischemic Stroke	1,165	Edaravone+Dexborneol	iasxzvhnsb(opnfzsgoen) = xfyeddmfcn rzrnczahgg (hlkmlfmshv ) View more	Superior	01 Mar 2021
				Edaravone	iasxzvhnsb(opnfzsgoen) = nuukeksghe rzrnczahgg (hlkmlfmshv )
NCT01929096 (Pubmed) Manual	Phase 2	Acute Ischemic Stroke	385	Edaravone Dexborneol	wiknsklgxw(yqixxfrvlz): P-Value = 0.6799 View more	Positive	22 Apr 2019
				Edaravone

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis