Randomised clinical trial: the efficacy of a transient receptor potential vanilloid 1 antagonist AZD1386 in human oesophageal pain

Aliment Pharmacol Ther. 2011 May;33(10):1113-22. doi: 10.1111/j.1365-2036.2011.04629.x. Epub 2011 Mar 16.

Abstract

Background: Many patients with gastro-oesophageal reflux disease (GERD) are hypersensitive to heat and acid and may respond insufficiently to standard treatment. Antagonists of the heat and acid receptor 'transient receptor potential vanilloid 1'(TRPV1) are a potential drug class for GERD treatment.

Aim: To investigate the effect of a TRPV1 antagonist (AZD1386) on experimentally induced oesophageal pain.

Methods: Twenty-two healthy men (20-31 years) participated in this randomised, placebo-controlled, double-blinded, crossover study examining the effects of a single-dose oral AZD1386 (30 and 95 mg). Subjects were block-randomised. On treatment days, participants were stimulated with painful heat, distension, electrical current and acid in the oesophagus. Heat and pressure pain on the forearm were somatic control stimuli.

Data analysis: intention-to-treat.

Results: A total of 21 participants completed the protocol and 1 voluntarily discontinued. In the oesophagus, both 30 and 95 mg of AZD1386 increased pain thresholds to heat stimuli 23% [95% confidence interval (CI): 10-38%] and 28%, respectively (CI: 14-43%). The skin heat tolerance was increased 2.1 °C (CI: 1.1-3.2 °C) after 30 mg AZD1386 and 4.0 °C (CI: 3.0-5.0 °C) after 95 mg. Heat analgesia persisted for 2.5 h. Pain thresholds to the other stimuli were unaffected by AZD1386. 50% reported 'feeling cold' and body temperature increased in all subjects exposed to 30 and 95 mg AZD1386 (mean increase 0.4±0.3 °C and 0.7±0.3 °C, respectively, P<0.05).

Conclusions: AZD1386 increased oesophageal and skin heat pain thresholds and had a safe adverse-event profile. This drug class may have a potential for treatment of GERD.

Trial registration: ClinicalTrials.gov NCT00711048.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analgesics / pharmacokinetics
  • Analgesics / therapeutic use*
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Esophageal Diseases / chemically induced
  • Esophageal Diseases / drug therapy*
  • Hot Temperature
  • Humans
  • Hyperalgesia / chemically induced
  • Hyperalgesia / drug therapy*
  • Male
  • Pain / drug therapy
  • Pain Measurement
  • TRPV Cation Channels / antagonists & inhibitors*
  • Young Adult

Substances

  • Analgesics
  • TRPV Cation Channels
  • TRPV1 protein, human

Associated data

  • ClinicalTrials.gov/NCT00711048