A Phase 2a, Randomized, Double-Blind Placebo-controlled, Parallel-group Study to Assess the Analgesic Efficacy and Safety of ASP0819 in Patients With Fibromyalgia

This study assessed analgesic efficacy of ASP0819 relative to placebo as well as the safety and tolerability.
This study assessed treatment differences in physical function as well as the improvements in overall subject status (e.g., fibromyalgia symptoms and global functioning) of ASP0819 relative to placebo.

开始日期2017-03-20

申办/合作机构

Astellas Pharma Global Development, Inc.

100 项与 ASP-0819 相关的临床结果

登录后查看更多信息

100 项与 ASP-0819 相关的转化医学

登录后查看更多信息

100 项与 ASP-0819 相关的专利（医药）

登录后查看更多信息

项与 ASP-0819 相关的文献（医药）

Journal of Pain Research3区 · 医学

<p>Efficacy and Safety of ASP0819 in Patients with Fibromyalgia: Results of a Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial</p>

3区 · 医学

ArticleOA

作者: Cai, Na ; Blauwet, Mary Beth ; Marek, Gerard J ; Blahunka, Paul ; Walzer, Mark ; Tracy, Katherine ; Arnold, Leslie M

PURPOSEASP0819 is a novel, non-opioid K_Ca3.1 channel opener that reverses abnormal nerve firing of primary sensory afferent nerves. Currently available treatments for fibromyalgia provide only modest relief and are accompanied by a host of adverse side effects.PATIENTS AND METHODSIn this phase 2a, double-blind trial (NCT03056690), adults meeting fibromyalgia diagnostic criteria were randomized 1:1 to receive either 15 mg/day of oral ASP0819 (n=91) or placebo (n=95). The primary endpoint was the change from baseline to Week 8 in the mean daily average pain score. Changes in the Fibromyalgia Impact Questionnaire Revised (FIQR) symptoms, function, and overall impact subscales, as well as changes in the patients' global impression of change, were secondary endpoints; treatment effects on FIQR total score and impact on sleep were exploratory analyses.RESULTSThere was no statistically significant difference between ASP0819 and placebo for the primary endpoint (P=0.086); however, ASP0819 versus placebo significantly improved daily average pain at Weeks 2, 6, and 7 (all P<0.05). Numerical improvements were observed on the FIQR total score and several sleep items showed statistically significant improvements with ASP0819 versus placebo. There were no major safety concerns with ASP0819. Headache was the most common treatment-emergent adverse event (TEAE) occurring in both study arms; most TEAEs were mild or moderate in severity and no TEAEs suggestive of potential drug abuse were observed, as assessed by TEAE reporting and/or safety evaluations. Withdrawal effects also were not observed.CONCLUSIONASP0819 demonstrated some signals suggestive of efficacy and had a good tolerability profile in patients with fibromyalgia. Further studies are required to determine if ASP0819 can be a novel non-opioid treatment option in this patient group.CLINICALTRIALSGOV REGISTRATIONNCT03056690.

Frontiers in Pain Research

Peripheral Voltage-Gated Cation Channels in Neuropathic Pain and Their Potential as Therapeutic Targets

Review

作者: Smith, Peter A ; Alles, Sascha R A

The persistence of increased excitability and spontaneous activity in injured peripheral neurons is imperative for the development and persistence of many forms of neuropathic pain. This aberrant activity involves increased activity and/or expression of voltage-gated Na+ and Ca2+ channels and hyperpolarization activated cyclic nucleotide gated (HCN) channels as well as decreased function of K+ channels. Because they display limited central side effects, peripherally restricted Na+ and Ca2+ channel blockers and K+ channel activators offer potential therapeutic approaches to pain management. This review outlines the current status and future therapeutic promise of peripherally acting channel modulators. Selective blockers of Nav1.3, Nav1.7, Nav1.8, Cav3.2, and HCN2 and activators of Kv7.2 abrogate signs of neuropathic pain in animal models. Unfortunately, their performance in the clinic has been disappointing; some substances fail to meet therapeutic end points whereas others produce dose-limiting side effects. Despite this, peripheral voltage-gated cation channels retain their promise as therapeutic targets. The way forward may include (i) further structural refinement of K+ channel activators such as retigabine and ASP0819 to improve selectivity and limit toxicity; use or modification of Na+ channel blockers such as vixotrigine, PF-05089771, A803467, PF-01247324, VX-150 or arachnid toxins such as Tap1a; the use of Ca2+ channel blockers such as TTA-P2, TTA-A2, Z 944, ACT709478, and CNCB-2; (ii) improving methods for assessing “pain” as opposed to nociception in rodent models; (iii) recognizing sex differences in pain etiology; (iv) tailoring of therapeutic approaches to meet the symptoms and etiology of pain in individual patients via quantitative sensory testing and other personalized medicine approaches; (v) targeting genetic and biochemical mechanisms controlling channel expression using anti-NGF antibodies such as tanezumab or re-purposed drugs such as vorinostat, a histone methyltransferase inhibitor used in the management of T-cell lymphoma, or cercosporamide a MNK 1/2 inhibitor used in treatment of rheumatoid arthritis; (vi) combination therapy using drugs that are selective for different channel types or regulatory processes; (vii) directing preclinical validation work toward the use of human or human-derived tissue samples; and (viii) application of molecular biological approaches such as clustered regularly interspaced short palindromic repeats (CRISPR) technology.

Journal of Pain Research3区 · 医学

A KCa3.1 Channel Opener, ASP0819, Modulates Nociceptive Signal Processing from Peripheral Nerves in Fibromyalgia-Like Pain in Rats

3区 · 医学

ArticleOA

作者: Oe, Tomoya ; Takeshita, Nobuaki ; Kiso, Tetsuo ; Kakimoto, Shuichiro

PURPOSEAlthough abnormal peripheral and central pain processing has been observed in fibromyalgia (FM) patients, the biomechanics and pathophysiology, surrounding the peripheral mechanism are not well understood. An intermediate conductance channel, K_Ca3.1, is expressed in peripheral sensory nerve fibers where it maintains the resting membrane potential and controls nerve firing, making it a plausible target for peripheral therapeutic interventions. ASP0819, a K_Ca3.1 channel opener, is an orally available molecular entity and is used in this investigation to elucidate the role of K_Ca3.1 in signal processing of pain in FM.METHODSHuman or rat K_Ca3.1 channel-expressing cells were used for evaluating the main action of the compound. Effects of the compound on withdrawal behavior by mechanical stimulation were examined in reserpine-induced myalgia (RIM) and vagotomy-induced myalgia (VIM) models of rats. In addition, in vivo electrophysiological analysis was performed to examine the peripheral mechanisms of action of the compound. Other pain models were also examined.RESULTSASP0819 increased the negative membrane potential in a concentration-dependent manner. Oral administration of ASP0819 significantly recovered the decrease in muscle pressure threshold in rat FM models of RIM and VIM. The in vivo electrophysiological experiments showed that Aδ- and C-fibers innervating the leg muscles in the RIM model demonstrated increased spontaneous and mechanically evoked firing compared with normal rats. Intravenous infusion of ASP0819 significantly reduced both the spontaneous activity and mechanically evoked responses in Aδ-fibers in the rat RIM model. ASP0819 significantly reduced the number of abdominal contractions as an indicator of abdominal pain behaviors in the rat visceral extension model and withdrawal responses in the osteoarthritis model, respectively.CONCLUSIONThese findings suggest that ASP0819 may be a promising analgesic agent with the ability to modulate peripheral pain signal transmission. Its use in the treatment of several pain conditions should be explored, chief amongst these being FM pain.

100 项与 ASP-0819 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
纤维肌痛	临床2期	-	Astellas Pharma, Inc.	-

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03056690 (Pubmed \| J Pain Res) 人工标引	临床2期	纤维肌痛	186	ASP-0819	(醖獵蓋簾獵鏇膚築獵選) = no statistically significant difference(P=0.086)； however, ASP0819 versus placebo significantly improved daily average pain at Weeks 2, 6, and 7 (all P<0.05). 醖膚網襯膚鹹廠夢壓窪 (網艱鏇鏇壓鏇鑰遞獵選 ) 更多	积极	2020-12-10
				Placebo
NCT03056690 (CTgov)	临床2期	纤维肌痛	186	placebo (Placebo)	簾繭鹹憲築簾壓鑰鹹範(遞構鹹衊積簾窪艱遞糧) = 鏇糧構窪鑰艱鏇範淵遞衊壓鑰鬱範選顧積鹽觸 (願壓願遞構鹹齋壓觸鬱, 糧築網醖顧製齋願廠糧 ~ 廠艱糧網選衊積獵膚憲) 更多	-	2021-03-03
				ASP0819 (ASP0819)	壓顧鬱範範繭鹹簾顧遞(鏇鑰鬱範鹹範憲淵糧艱) = 齋壓製蓋齋鹹網醖艱衊鏇襯襯齋壓鬱網膚築窪 (簾襯壓積壓鏇鏇顧襯膚, 醖夢觸衊醖願選醖獵鹽 ~ 蓋齋醖衊餘願願糧憲繭) 更多