Delving into the Latest Updates on ONO-8539 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

EP1

Action

antagonists

Mechanism

EP1 antagonists(Prostanoid EP1 receptor antagonists)

Therapeutic Areas

Digestive System DisordersMouth and Tooth DiseasesOtorhinolaryngologic Diseases+ [2]

Active Indication-

Inactive Indication

HypersensitivityNon-erosive gastro-esophageal reflux diseaseUrinary Bladder, Overactive

Originator Organization

Ono Pharmaceutical Co., Ltd.

Active Organization-

Inactive Organization

Ono Pharmaceutical Co., Ltd.

License Organization-

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Background/Aims: Transient lower esophageal sphincter relaxations (TLESRs) are the major cause of gastroesophageal reflux. Recently, an EP1 receptor antagonist, ONO-8539, showed the reduction of TLESRs in monkeys. However, its effect on TLESRs in humans remains unclear. This study investigated the effect of ONO-8539 on postprandial TLESRs in healthy male subjects. Methods: Twenty-seven subjects participated in this placebo-controlled, cross-over study. The subjects received either placebo or ONO-8539 (450 mg) after a standardized breakfast. A 30-min basal recording was performed 4 h after drug administration. Subsequently, TLESR recordings were performed after a high-fat test meal for 3 h. The examination was repeated at least 7 days from the first evaluation for washout. Results: Thirteen patients were ultimately analyzed. The basal lower esophageal sphincter pressure was not different between the 2 groups (16.3 and 18.0 mm Hg for placebo and ONO-8539, respectively; p = 0.88). ONO-8539 significantly reduced the number of TLESRs from 15.0 to 12.0 for 3 h (p < 0.05). The proportion of terminating events of TLESRs was significantly different between the 2 groups (p < 0.05). No events and swallowing terminated more TLESRs with ONO-8539 than with placebo. Conclusions: ONO-8539 suppressed TLESRs mildly. EP1 receptor may be involved with the mechanism of human TLESRs.

01 Oct 2017·Journal of GastroenterologyQ1 · MEDICINE

A novel prostanoid EP1 receptor antagonist, ONO-8539, reduces acid-induced heartburn symptoms in healthy male volunteers: a randomized clinical trial

Q1 · MEDICINE

Article

Author: Oshima, Tadayuki ; Ohda, Yoshio ; Watari, Jiro ; Yamasaki, Takahisa ; Miwa, Hiroto ; Tomita, Toshihiko ; Sei, Hiroo ; Kondo, Takashi ; Fukui, Hirokazu

BACKGROUNDPatients with proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD) have unmet clinical needs. Recently, we reported that esophageal prostaglandin E₂ (PGE₂) plays a crucial role in the generation of heartburn. In the present study, we focused on the PGE₂ receptor, EP1, and investigated the effects of ONO-8539, a novel EP1 receptor antagonist, on heartburn symptoms in healthy male volunteers.METHODSThis prospective, double-blind, placebo-controlled, two-period crossover study was performed in 20 healthy male subjects. The novel prostanoid EP1 receptor antagonist, ONO-8539 (450 mg), was administered once 4 h prior to acid perfusion test. During the test, hydrochloric acid (0.15 mol l^-1) was perfused into the lower esophagus for 30 min. Acid perception threshold was quantified by the time to first sensation of heartburn and intensity of GI symptoms determined using a validated categorical rating scale, and the area under the curve (AUC) as the total symptom score.RESULTSONO-8539 significantly reduced a total heartburn symptom score, not other upper GI symptom scores, during acid perfusion compared with placebo (AUC for heartburn, 85.0 ± 10.6 for placebo and 56.5 ± 7.2 for ONO-8539; P < 0.01), and significantly extended the time to first sensation of heartburn compared with placebo (5.7 ± 4.3 min for placebo and 9.7 ± 7.2 min for ONO-8539; P < 0.05).CONCLUSIONSONO-8539 attenuated acid-induced heartburn in healthy male subjects, suggesting that EP1 receptors play a role in generation of heartburn symptoms. ONO-8539 is a potential novel therapeutic option for controlling heartburn symptoms in GERD patients. Clinical Trials Registry No: UMIN000015753.

01 Jan 2014·Journal of UrologyQ1 · MEDICINE

Phase II Study on the Efficacy and Safety of the EP1 Receptor Antagonist ONO-8539 for Nonneurogenic Overactive Bladder Syndrome

Q1 · MEDICINE

Article

Author: Andersson, K.-E. ; Deacon, S. ; Small, M. ; Chapple, C.R. ; Masuda, T. ; Kuwayama, T. ; Radziszewski, P. ; Abrams, P.

PURPOSEWe evaluated the efficacy, safety and tolerability of the EP1 receptor antagonist ONO-8539 in patients with overactive bladder syndrome.MATERIALS AND METHODSThis was a 12-week, randomized, double-blind, placebo controlled, parallel group, multicenter study with a 2-week single blind placebo run-in phase. The 435 patients were randomized to receive twice daily ONO-8539 (30, 100 or 300 mg), placebo or once daily tolterodine (4 mg).RESULTSAt the end of the 12-week treatment no statistically significant difference was found between ONO-8539 and placebo in the change from baseline in the number of micturitions per 24 hours. The primary end points for 30, 100 and 300 mg ONO-8539, and placebo were -1.02, -1.53, -1.31 and -1.40, respectively. There was no statistically significant difference between any ONO-8539 group and placebo in the change from baseline in the number of urgency or urinary urgency incontinence episodes per 24 hours, or the mean volume voided per micturition, which were secondary end points. Statistically significant differences for tolterodine vs placebo were observed in the change from baseline in the number of micturitions (p = 0.045), urgency episodes (p = 0.04) and mean volume voided per micturition (p <0.001). The incidence of adverse events was 54.1% in the placebo group, 43.0% to 54.0% in the ONO-8539 groups and 46.6% in the tolterodine group. The intensity of adverse events was similar among the treatment groups. Similar to other treatments, the most frequently reported adverse events after ONO-8539 were nasopharyngitis and diarrhea.CONCLUSIONSThe results of this study, which to our knowledge represents the first evaluation of ONO-8539 in patients with overactive bladder, suggest a minimal role for EP1 receptor antagonism in the management of overactive bladder syndrome.

100 Deals associated with ONO-8539

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Non-erosive gastro-esophageal reflux disease	Phase 2	United Kingdom	Ono Pharmaceutical Co., Ltd.	01 Dec 2012
Urinary Bladder, Overactive	Phase 2	Germany	Ono Pharmaceutical Co., Ltd.	01 Apr 2009
Urinary Bladder, Overactive	Phase 2	Ukraine	Ono Pharmaceutical Co., Ltd.	01 Apr 2009
Urinary Bladder, Overactive	Phase 2	Russia	Ono Pharmaceutical Co., Ltd.	01 Apr 2009
Urinary Bladder, Overactive	Phase 2	Hungary	Ono Pharmaceutical Co., Ltd.	01 Apr 2009
Urinary Bladder, Overactive	Phase 2	Romania	Ono Pharmaceutical Co., Ltd.	01 Apr 2009
Urinary Bladder, Overactive	Phase 2	Czechia	Ono Pharmaceutical Co., Ltd.	01 Apr 2009
Urinary Bladder, Overactive	Phase 2	Poland	Ono Pharmaceutical Co., Ltd.	01 Apr 2009
Urinary Bladder, Overactive	Phase 2	Netherlands	Ono Pharmaceutical Co., Ltd.	01 Apr 2009
Urinary Bladder, Overactive	Phase 2	Sweden	Ono Pharmaceutical Co., Ltd.	01 Apr 2009