Fatty Acid Amide Hydrolase Inhibitor Treatment in Men With Chronic Prostatitis/Chronic Pelvic Pain Syndrome: An Adaptive Double-blind, Randomized Controlled Trial

Urology. 2017 May:103:191-197. doi: 10.1016/j.urology.2017.02.029. Epub 2017 Feb 27.


Objective: To examine the effect of a peripherally active fatty acid amide hydrolase (FAAH) inhibitor ASP3652 on safety and efficacy outcomes in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Inhibition of FAAH is hypothesized to reduce the excitability of urinary tract afferents including nociceptors.

Materials and methods: In this adaptive, randomized, double-blind, placebo-controlled study, adult male patients with moderate to severe CP/CPPS were treated for 12 weeks with an oral dose of ASP3652 (25, 75, 150, or 300 mg twice daily, or 300 mg once daily), or placebo. A Bayesian model was used for adaptive prospective modeling of randomization, study continuation decisions, and analysis of the efficacy variables.

Results: The study was stopped for futility at preplanned interim analysis when 239 patients were randomized (226 were included in the intention-to-treat set): the 25 mg group showed the largest reduction of the primary end point National Institutes of Health Chronic Prostatitis Symptom Index total score (7.0 points), but the placebo group showed a mean reduction of 7.3 points (difference: 0.3 [95% confidence interval: -1.9, 2.6]). Micturition outcomes improved compared with placebo in all ASP3652 groups; for example, in the 300 mg twice daily group, voiding frequency decreased by -1.10 (95% CI: -2.0, -0.2) voids/24 hours vs placebo. Safety outcomes were comparable across the treatment groups.

Conclusion: ASP3652 was generally safe and well-tolerated. It did not show efficacy on pain symptoms in patients with CP/CPPS. However, the results indicate that FAAH inhibition may attenuate lower urinary tract symptoms. Dedicated studies in patients with lower urinary tract dysfunction are needed to confirm this.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Amidohydrolases / antagonists & inhibitors*
  • Biological Availability
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Monitoring / methods
  • Enzyme Inhibitors* / administration & dosage
  • Enzyme Inhibitors* / pharmacokinetics
  • Humans
  • Lower Urinary Tract Symptoms* / diagnosis
  • Lower Urinary Tract Symptoms* / drug therapy
  • Lower Urinary Tract Symptoms* / etiology
  • Male
  • Middle Aged
  • Pelvic Pain* / diagnosis
  • Pelvic Pain* / drug therapy
  • Pelvic Pain* / etiology
  • Prostatitis* / complications
  • Prostatitis* / diagnosis
  • Prostatitis* / drug therapy
  • Treatment Outcome


  • Enzyme Inhibitors
  • Amidohydrolases
  • fatty-acid amide hydrolase