Delving into the Latest Updates on ASP-8477 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

FAAH

Mechanism

FAAH inhibitors(Anandamide amidohydrolase inhibitors)

Therapeutic Areas

Nervous System DiseasesEndocrinology and Metabolic Disease

Active Indication-

Inactive Indication

Diabetic peripheral neuropathic painNeuralgia, Postherpetic

Originator Organization

Astellas Pharma, Inc.

Active Organization-

Inactive Organization

Astellas Pharma Europe Ltd.

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC18H19N3O3

InChIKeyPLCMZPFTMOAGOE-UHFFFAOYSA-N

CAS Registry906737-25-5

The purpose of this study is to assess the painkilling efficacy of ASP8477 relative to mock (placebo) in patients that have been diagnosed with painful diabetic peripheral neuropathy or postherpetic neuralgia determined by the change in the average daily pain intensity in patients that initially respond favorably to treatment with ASP8477.

Start Date24 Feb 2014

Sponsor / Collaborator

Astellas Pharma Europe Ltd.

NCT02220777 / CompletedPhase 1

A Double-blind, Randomized, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Oral Doses of ASP8477 in Healthy Postmenopausal Females and Healthy Young Vasectomized Males, Including a Food Effect Part and a Part to Investigate the Interaction Between ASP8477 and Omeprazole

This is a 4-part study. Part I assesses the safety and tolerability of single ascending doses of ASP8477 or a placebo under fasted conditions in postmenopausal subjects. Part II is similar to part I except that the study is conducted in young, vasectomized males.
Part III assesses the effect of food (fed or fasted conditions) on ASP8477 in postmenopausal subjects.
Part IV assesses the drug-drug interaction between ASP8477 and omeprazole in postmenopausal subjects.

Start Date01 Nov 2010

Sponsor / Collaborator

Astellas Pharma Europe Ltd.

100 Clinical Results associated with ASP-8477

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100 Translational Medicine associated with ASP-8477

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100 Patents (Medical) associated with ASP-8477

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4

Literatures (Medical) associated with ASP-8477

01 Aug 2020·European Journal of PharmacologyQ3 · MEDICINE

ASP8477, a fatty acid amide hydrolase inhibitor, exerts analgesic effects in rat models of neuropathic and dysfunctional pain

Q3 · MEDICINE

Article

Author: Watabiki, Tomonari ; Sekizawa, Toshihiro ; Kiso, Tetsuo

Exogenous cannabinoid receptor agonists are clinically effective for treating chronic pain but frequently cause side effects in the central nervous system. Fatty acid amide hydrolase (FAAH) is a primary catabolic enzyme for anandamide, an endogenous cannabinoid agonist. 3-Pyridyl 4-(phenylcarbamoyl)piperidine-1-carboxylate (ASP8477) is a potent and selective FAAH inhibitor that is orally active and able to increase the brain anandamide level and is effective in rat models of neuropathic and osteoarthritis pain without causing motor coordination deficits. In the present study, we examined the pharmacokinetics and pharmacodynamics, analgesic spectrum in pain models, and the anti-nociceptive mechanism of ASP8477. Single and four-week repeated oral administration of ASP8477 ameliorated mechanical allodynia in spinal nerve ligation rats with similar improvement rates. Further, single oral administration of ASP8477 improved thermal hyperalgesia and cold allodynia in chronic constriction nerve injury rats. ASP8477 also restored muscle pressure thresholds in reserpine-induced myalgia rats. This analgesic effect of ASP8477 persisted for at least 4 h, consistent with the inhibitory effect observed in an ex vivo study using rat brain as well as the increasing effect on oleoylethanolamide and palmitoylethanolamide levels but not the ASP8477 concentration in rat brain. ASP8477 also improved α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-, N-methyl-D-aspartic acid (NMDA)-, prostaglandin E₂-, prostaglandin F_2α-, and bicuculline-induced allodynia in mice, showing broader analgesic spectra than existing drugs. In contrast, however, ASP8477 did not affect acute pain. These results indicate that the FAAH inhibitor ASP8477 exerts analgesic effects on neuropathic and dysfunctional pain, and its pharmacological properties are suitable for use in treating chronic pain.

01 Jun 2018·Pain MedicineQ3 · MEDICINE

A Randomized, Double-Blind, Placebo- and Active Comparator-Controlled Phase I Study of Analgesic/Antihyperalgesic Properties of ASP8477, a Fatty Acid Amide Hydrolase Inhibitor, in Healthy Female Subjects

Q3 · MEDICINE

Article

Author: Yassen, Ashraf ; Passier, Paul ; Schaffler, Klaus ; Reeh, Peter

ObjectivesTo evaluate the analgesic/antihyperalgesic effect of ASP8477.DesignRandomized, double-blind, double-dummy, cross-over, placebo- and active comparator-controlled study.SettingHPR Dr. Schaffler GmbH, Munich, Germany.SubjectsHealthy female subjects aged 18-65 years.MethodsEligible subjects were randomly assigned to one of six treatment sequences and received multiple ascending doses of ASP8477, duloxetine, and placebo over three treatment periods (each consisting of 21-day dosing separated by 14-day washout periods). On the last day of each dose level, laser evoked potentials (LEPs) and visual analog scales (VAS pain) on capsaicin-treated skin at baseline and at multiple postdose time points were assessed. The primary end point was the difference in LEP N2-P2 peak-to-peak (PtP) amplitudes for ASP8477 100 mg vs placebo.ResultsTwenty-five subjects were randomized. In all subjects, LEP N2-P2 PtP amplitudes were numerically lower for ASP8477 100 mg vs placebo (P = 0.0721); in subjects who demonstrated positive capsaicin skin effects, a greater mean difference of -2.24 µV (P = 0.0146) was observed. Across all doses, LEP N2-P2 PtP amplitudes were lower for duloxetine compared with ASP8477 (mean difference -3.80 µV; P < 0.0001) or placebo (mean difference -5.21 µV; P < 0.0001). The effect of ASP8477 (all doses) on down-scoring the VAS pain score was significant compared with placebo (mean difference -2.55%; P < 0.0007).ConclusionsASP8477 was well tolerated in this study. Analysis of all subjects did not demonstrate a significant difference in LEP for ASP8477 100 mg over placebo but did in subjects who demonstrated positive capsaicin skin effects.

01 Dec 2017·Pain MedicineQ3 · MEDICINE

The MOBILE Study—A Phase IIa Enriched Enrollment Randomized Withdrawal Trial to Assess the Analgesic Efficacy and Safety of ASP8477, a Fatty Acid Amide Hydrolase Inhibitor, in Patients with Peripheral Neuropathic Pain

Q3 · MEDICINE

Article

Author: Liosatos, Maggie ; Bradford, Daniel ; Blahunka, Paul ; Ernault, Etienne ; Moseley, Jennifer ; Stirling, Anjali ; Smith, Mike D ; Tracy, Katherine

OBJECTIVETo evaluate the analgesic efficacy and safety of ASP8477 in patients with peripheral neuropathic pain (PNP).DESIGNEnriched enrollment randomized withdrawal.SETTINGCenters in Poland (four), Czech Republic (six), and the United Kingdom (two).SUBJECTSPatients aged 18 years or older with PNP resulting from painful diabetic peripheral neuropathy or postherpetic neuralgia.METHODSA four-week screening period followed by a single-blind period (six-day dose titration and three-week maintenance period with ASP8477 [20/30 mg BID]). Treatment responders (defined as a ≥30% decrease in the mean average daily pain intensity during the last three days of the single-blind period) were stratified by disease and randomized to receive placebo or continue ASP8477 during a three-week, double-blind, randomized withdrawal period. The primary end point was change in mean 24-hour average numeric pain rating scale (NPRS) from baseline to end of double-blind period.RESULTSAmong 132 patients who enrolled, 116 entered the single-blind period and 63 (ASP8477, N = 31; placebo, N = 32) completed the double-blind period. There was no difference in mean 24-hour average NPRS score (P = 0.644) or in time-to-treatment failure (P = 0.485) between ASP8477 and placebo. During the single-blind period, 57.8% of patients were treatment responders. ASP8477 was well tolerated. During the single-blind period, 22% of patients experienced at least one treatment-related adverse event (TEAE); during the double-blind period, 8% in the ASP8477 arm and 18% in the placebo arm experienced at least one TEAE.CONCLUSIONSASP8477 was well tolerated in patients with PNP; however, ASP8477 did not demonstrate a significant treatment difference compared with placebo.

100 Deals associated with ASP-8477

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetic peripheral neuropathic pain	Phase 2	DE	Astellas Pharma Europe Ltd.	24 Feb 2014
Diabetic peripheral neuropathic pain	Phase 2	PL	Astellas Pharma Europe Ltd.	24 Feb 2014
Diabetic peripheral neuropathic pain	Phase 2	CZ	Astellas Pharma Europe Ltd.	24 Feb 2014
Neuralgia, Postherpetic	Phase 2	CZ	Astellas Pharma Europe Ltd.	24 Feb 2014
Neuralgia, Postherpetic	Phase 2	DE	Astellas Pharma Europe Ltd.	24 Feb 2014
Neuralgia, Postherpetic	Phase 2	GB	Astellas Pharma Europe Ltd.	24 Feb 2014
Neuralgia, Postherpetic	Phase 2	PL	Astellas Pharma Europe Ltd.	24 Feb 2014