title: Fatty Acid Amide Hydrolase Inhibitor Treatment in Men With Chronic Prostatitis/Chronic Pelvic Pain Syndrome: An Adaptive Double-blind, Randomized Controlled Trial.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Clinic for Urology, Pediatric Urology and Andrology, Justus-Liebig-University, Giessen, Germany.
authors.forename: Florian M E
authors.initials: FME
authors.lastname: Wagenlehner
authors.affiliation: Astellas Pharma Europe B.V., Leiden, The Netherlands. Electronic address: olivier.vantill@astellas.com.
authors.forename: J W Olivier
authors.initials: JWO
authors.lastname: van Till
authors.affiliation: Astellas Pharma Europe B.V., Leiden, The Netherlands.
authors.forename: Jos G A
authors.initials: JGA
authors.lastname: Houbiers
authors.affiliation: Biostatistics Department, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Reynaldo V
authors.initials: RV
authors.lastname: Martina
authors.affiliation: Astellas Pharma Europe B.V., Leiden, The Netherlands.
authors.forename: Dirk P
authors.initials: DP
authors.lastname: Cerneus
authors.affiliation: Astellas Pharma Europe B.V., Leiden, The Netherlands.
authors.forename: Joost H J M
authors.initials: JHJM
authors.lastname: Melis
authors.affiliation: Centrum Medyczne Szpital Sw Rodziny Sp z o.o., Lodz, Poland.
authors.forename: Antoni
authors.initials: A
authors.lastname: Majek
authors.affiliation: Stradins Clinical University Hospital, Riga, Latvia.
authors.forename: Egils
authors.initials: E
authors.lastname: Vjaters
authors.affiliation: Androgeos, Praha, Czech Republic.
authors.forename: Michael
authors.initials: M
authors.lastname: Urban
authors.affiliation: Vilnius University Hospital "Santariskiu Klinikos" Urology Centre, Vilnius, Lithuania.
authors.forename: Henrikas
authors.initials: H
authors.lastname: Ramonas
authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic Foundation, Cleveland, OH.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Shoskes
authors.affiliation: Department of Urology, Queen's University, Kingston, ON, Canada.
authors.forename: J Curtis
authors.initials: JC
authors.lastname: Nickel
mesh_terms: D000328:Adult; D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016903:Drug Monitoring / Q000379:methods; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D059411:Lower Urinary Tract Symptoms / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D008297:Male; D008875:Middle Aged; D017699:Pelvic Pain / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D011472:Prostatitis / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy; D016896:Treatment Outcome; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D004791:Enzyme Inhibitors; D000099252:Fatty Acid Amide Hydrolases