title: Randomized clinical trial: efficacy and safety of PPC-5650 on experimental esophageal pain and hyperalgesia in healthy volunteers.
abstract: OBJECTIVE
  Gastroesophageal reflux disease (GERD) is a common condition associated with symptoms as heart burn, regurgitation, chest pain, and gastrointestinal discomfort. PPC-5650 is a new pharmacological agent that can modulate acid-sensing ion channel activity, potentially leading to reduction in the pain signal. In healthy volunteers the esophagus was sensitized with acid to mimic GERD with the aims: 1) to assess the efficacy of a single bolus of PPC-5650 locally applied to the esophagus using multimodal pain stimulations, and 2) to assess the safety profile of PPC-5650.
  
  
  METHODS
  The study was a randomized, double-blinded, placebo-controlled, crossover trial in healthy males. Esophageal electrical, thermal, mechanical, and chemical stimulations were performed, pain perception was rated, and referred pain areas were drawn. Sensitization was induced by intraluminal esophageal acid perfusions. Adverse events were registered.
  
  
  RESULTS
  Twenty-five healthy males completed the study (mean age 23.4 ± 2.0 years). About 90 min after drug administration, PPC-5650 increased the volume tolerated at moderate pain during mechanical stimulation compared to placebo (difference 13.5, 95% CI: 0.58-26.47, p = 0.04), but there was no effects on thermal-, electrical-, and chemical-induced pain (all p > 0.05). PPC-5650 did not affect referred pain areas to any stimulation (all p > 0.05). Ten participants reported adverse events during the placebo treatment period, and nine participants reported adverse events during the PPC-5650 treatment period (p = 0.8).
  
  
  CONCLUSIONS
  Sensitization to mechanical stimulation of the esophagus was reduced by PPC-5650 compared to placebo. The overall safety and tolerability of PPC-5650 was acceptable. Thus, PPC-5650 may play a role in the future treatment of patients with GERD.
authors.affiliation: Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital , Aalborg , Denmark.
authors.forename: Anne Estrup
authors.initials: AE
authors.lastname: Olesen
authors.forename: Lecia Møller
authors.initials: LM
authors.lastname: Nielsen
authors.forename: Isabelle Myriam
authors.initials: IM
authors.lastname: Larsen
authors.forename: Asbjørn Mohr
authors.initials: AM
authors.lastname: Drewes
mesh_terms: D062646:Acid Sensing Ion Channel Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions; D004947:Esophagus / Q000187:drug effects*; D005764:Gastroesophageal Reflux / Q000188:drug therapy*; D064368:Healthy Volunteers; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy*; D008297:Male; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D017288:Pain Threshold; D055815:Young Adult
chemical_list: D062646:Acid Sensing Ion Channel Blockers
keywords: acid-sensing ion channel inhibitors; gastroesophageal reflux disease; hyperalgesia; pain; therapeutics