A novel prostanoid EP1 receptor antagonist, ONO-8539, reduces acid-induced heartburn symptoms in healthy male volunteers: a randomized clinical trial.
J Gastroenterol
; 52(10): 1081-1089, 2017 10.
Article
em En
| MEDLINE
| ID: mdl-28120127
ABSTRACT
BACKGROUND:
Patients 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.METHODS:
This 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.RESULTS:
ONO-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).CONCLUSIONS:
ONO-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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tiazóis
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Benzoatos
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Fármacos Gastrointestinais
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Refluxo Gastroesofágico
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Receptores de Prostaglandina E Subtipo EP1
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Azia
/
Indenos
Tipo de estudo:
Clinical_trials
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Diagnostic_studies
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Observational_studies
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Prognostic_studies
Limite:
Adult
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Gastroenterol
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Japão