PMID- 28120127
OWN - NLM
STAT- MEDLINE
DCOM- 20190128
LR  - 20190215
IS  - 1435-5922 (Electronic)
IS  - 0944-1174 (Linking)
VI  - 52
IP  - 10
DP  - 2017 Oct
TI  - A novel prostanoid EP1 receptor antagonist, ONO-8539, reduces acid-induced 
      heartburn symptoms in healthy male volunteers: a randomized clinical trial.
PG  - 1081-1089
LID - 10.1007/s00535-017-1308-3 [doi]
AB  - BACKGROUND: Patients with proton pump inhibitor (PPI)-refractory gastroesophageal 
      reflux disease (GERD) have unmet clinical needs. Recently, we reported that 
      esophageal prostaglandin E(2) (PGE(2)) plays a crucial role in the generation of 
      heartburn. In the present study, we focused on the PGE(2) 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.
FAU - Kondo, Takashi
AU  - Kondo T
AD  - Division of Gastroenterology, Department of Internal Medicine, Hyogo College of 
      Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
FAU - Sei, Hiroo
AU  - Sei H
AD  - Division of Gastroenterology, Department of Internal Medicine, Hyogo College of 
      Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
FAU - Yamasaki, Takahisa
AU  - Yamasaki T
AD  - Division of Gastroenterology, Department of Internal Medicine, Hyogo College of 
      Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
FAU - Tomita, Toshihiko
AU  - Tomita T
AD  - Division of Gastroenterology, Department of Internal Medicine, Hyogo College of 
      Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
FAU - Ohda, Yoshio
AU  - Ohda Y
AD  - Division of Gastroenterology, Department of Internal Medicine, Hyogo College of 
      Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
FAU - Oshima, Tadayuki
AU  - Oshima T
AD  - Division of Gastroenterology, Department of Internal Medicine, Hyogo College of 
      Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
FAU - Fukui, Hirokazu
AU  - Fukui H
AD  - Division of Gastroenterology, Department of Internal Medicine, Hyogo College of 
      Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
FAU - Watari, Jiro
AU  - Watari J
AD  - Division of Gastroenterology, Department of Internal Medicine, Hyogo College of 
      Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
FAU - Miwa, Hiroto
AU  - Miwa H
AD  - Division of Gastroenterology, Department of Internal Medicine, Hyogo College of 
      Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan. 
      miwahgi@hyo-med.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20170124
PL  - Japan
TA  - J Gastroenterol
JT  - Journal of gastroenterology
JID - 9430794
RN  - 0 (Benzoates)
RN  - 0 (Gastrointestinal Agents)
RN  - 0 (Indenes)
RN  - 0 (Receptors, Prostaglandin E, EP1 Subtype)
RN  - 0 (Thiazoles)
RN  - 94W010PZ1Z (ONO-8539)
SB  - IM
MH  - Adult
MH  - Benzoates/*therapeutic use
MH  - Cross-Over Studies
MH  - Double-Blind Method
MH  - Gastroesophageal Reflux/*drug therapy/pathology
MH  - Gastrointestinal Agents/*pharmacology
MH  - Heartburn/*drug therapy/pathology
MH  - Humans
MH  - Indenes/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Prospective Studies
MH  - Receptors, Prostaglandin E, EP1 Subtype/*antagonists & inhibitors/metabolism
MH  - Thiazoles/*therapeutic use
MH  - Time Factors
MH  - Treatment Outcome
MH  - Young Adult
OTO - NOTNLM
OT  - EP1
OT  - GERD
OT  - Heartburn
OT  - ONO-8539
OT  - PGE2
EDAT- 2017/01/26 06:00
MHDA- 2019/01/29 06:00
CRDT- 2017/01/26 06:00
PHST- 2016/07/21 00:00 [received]
PHST- 2017/01/11 00:00 [accepted]
PHST- 2017/01/26 06:00 [pubmed]
PHST- 2019/01/29 06:00 [medline]
PHST- 2017/01/26 06:00 [entrez]
AID - 10.1007/s00535-017-1308-3 [pii]
AID - 10.1007/s00535-017-1308-3 [doi]
PST - ppublish
SO  - J Gastroenterol. 2017 Oct;52(10):1081-1089. doi: 10.1007/s00535-017-1308-3. Epub 
      2017 Jan 24.