Author: Noda, Naoto ; Shibue, Yuta ; Takagaki, Takeshi ; Haranaka, Miwa ; Hamatani, Tatsuto ; Kitamura, Atsushi ; Ogama, Yoichiro ; Kakuyama, Hiroyoshi

AbstractEPI‐589 attenuates oxidative stress due to the radical scavenging activity of the reduced form and affects mitochondrial energy metabolism as a substrate of quinone‐oxidoreductases. Given the effects of EPI‐589 on oxidative stress and mitochondrial dysfunction, EPI‐589 shows promise as a potential therapy for patients with amyotrophic lateral sclerosis. This phase 1 study evaluated the safety, tolerability, and pharmacokinetic profiles of EPI‐589. Sixty‐eight healthy participants were randomly assigned to EPI‐589 or placebo. All adverse events were mild or moderate in severity, and no severe adverse events were reported. After single‐dose administration under fasting conditions, time to maximum plasma concentration (tmax) occurred 0.25 to 1.00 hour after administration. Both peak plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC) were approximately linear with increases in single doses over a dose range of 250–1000 mg. Under fed conditions, the Cmax decreased to 62.6% of the Cmax under fasting conditions, the AUC was slightly increased, and the tmax was delayed by 1 hour. When EPI‐589 was administered daily on days 1 and 7 with twice‐daily dosing on days 2 through 6, the plasma trough concentration appeared to reach steady state by day 3. At both doses studied (500 mg twice daily and 750 mg twice daily), Cmax, tmax, and AUC were generally comparable between day 1 and day 7 and between the Japanese and White participants. EPI‐589 was well tolerated as a single daily dose up to 1000 mg and as twice‐daily doses up to 750 mg, with a linear pharmacokinetic profile.

JMIR Research Protocols

An Exploratory Trial of EPI-589 in Amyotrophic Lateral Sclerosis (EPIC-ALS): Protocol for a Multicenter, Open-Labeled, 24-Week, Single-Group Study

Article

Author: Sobue, Gen ; Kawai, Hisashi ; Miyamoto, Ryosuke ; Fujita, Koji ; Morino, Hiroyuki ; Atsuta, Naoki ; Kanazawa, Yuki ; Sato, Yasutaka ; Kagimura, Tatsuo ; Oki, Ryosuke ; Mochizuki, Hideki ; Yagi, Kenta ; Osaki, Yusuke ; Nagano, Seiichi ; Doyu, Manabu ; Haji, Shotaro ; Harada, Masafumi ; Hamatani, Tatsuto ; Sakaguchi, Satoshi ; Yanagawa, Hiroaki ; Arisawa, Atsuko ; Matsumoto, Yuki ; Izumi, Yuishin

BackgroundAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder, with its currently approved drugs, including riluzole and edaravone, showing limited therapeutic effects. Therefore, safe and effective drugs are urgently necessary. EPI-589 is an orally available, small-molecule, novel redox-active agent characterized by highly potent protective effects against oxidative stress with high blood-brain barrier permeability. Given the apparent oxidative stress and mitochondrial dysfunction involvement in the pathogenesis of ALS, EPI-589 may hold promise as a therapeutic agent.ObjectiveThis protocol aims to describe the design and rationale for the EPI-589 Early Phase 2 Investigator-Initiated Clinical Trial for ALS (EPIC-ALS).MethodsEPIC-ALS is an explorative, open-labeled, single-arm trial that evaluates the safety and tolerability of EPI-589 in patients with ALS. This trial consists of 12-week run-in, 24-week treatment, and 4-week follow-up periods. Patients will receive 500 mg of EPI-589 3 times daily over the 24-week treatment period. Clinical assessments include the mean monthly change of Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised total score. The biomarkers are selected to analyze the effect on oxidative stress and neuronal damage. The plasma biomarkers are 8-hydroxy-2′-deoxyguanosine (8-OHdG), 3-nitrotyrosine (3-NT), neurofilament light chain (NfL), phosphorylated neurofilament heavy chain (pNfH), homocysteine, and creatinine. The cerebrospinal fluid biomarkers are 8-OHdG, 3-NT, NfL, pNfH, and ornithine. The magnetic resonance biomarkers are fractional anisotropy in the corticospinal tract and N-acetylaspartate in the primary motor area.ResultsThis trial began data collection in September 2021 and is expected to be completed in October 2023.ConclusionsThis study can provide useful data to understand the characteristics of EPI-589.Trial RegistrationJapan Primary Registries Network jRCT2061210031; tinyurl.com/2p84emu6International Registered Report Identifier (IRRID)DERR1-10.2196/42032

100 Deals associated with EPI-589

External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Amyotrophic Lateral Sclerosis	Phase 2	-	Sumitomo Pharma Co., Ltd.	-
Parkinson Disease	Discovery	GB	Edison Pharmaceuticals, Inc.	17 May 2016
Parkinson Disease	Discovery	DE	Edison Pharmaceuticals, Inc.	17 May 2016
Parkinson Disease	Discovery	US	Edison Pharmaceuticals, Inc.	17 May 2016

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


Pubmed Manual	Phase 1	Amyotrophic Lateral Sclerosis	68	EPI 589	(fcvzvmigqj) = All adverse events were mild or moderate in severity, and no severe adverse events were reported qvlfizoeze (hsxuefjhod )	Positive	21 Aug 2022
Pubmed Manual	Phase 1	Amyotrophic Lateral Sclerosis	68	Placebo		Positive	21 Aug 2022
NCT02462603 (CTgov)	Phase 2	Parkinson Disease	44	PTC-589	sgihqhoydh(uhlrllyowa) = ultifhntgn zkgdadcalh (saolgkpetu, ggwpmqjqfi - smkcuftvra) View more	-	03 May 2022
NCT02460679 (EPI-589, CTgov)	Phase 2	Amyotrophic Lateral Sclerosis	19	EPI-589	mvrrwxppmu(iennttnwor) = wdimjfaecx hxpycirwbp (kjfyvpqaeu, pelchajpkp - uznsxtwtaw) View more	-	23 Sep 2020

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