Fatty Acid Amide Hydrolase Inhibitor Treatment in Men with Chronic Prostatitis/Chronic Pelvic Pain Syndrome, an Adaptive Double-Blind Randomized Controlled Trial

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.

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 300mg twice daily [BID], or 300mg once daily) or placebo. A Bayesian model was used for adaptive prospective modeling of randomization, study continuation decisions and analysis of the efficacy variables.

The study was stopped for futility at pre-planned interim analysis when 239 patients were randomized (226 were included in the intention-to-treat set): the 25mg group showed the largest reduction of the primary endpoint NIH-CPSI 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 to 2.6]). Micturition outcomes improved compared to placebo in all ASP3652 groups, e.g., in the 300mg bis in die (BID, twice daily) group voiding frequency decreased by -1.10 (95% CI -2.0 to -0.2) voids/24hr vs. placebo. Safety outcomes were comparable across the treatment groups.

ASP3652 was generally safe and well-tolerated. It did not show efficacy on pain symptoms in patients with CP/CPPS. However, 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.

Urology. 2017 Feb 27 [Epub ahead of print]

Florian M E Wagenlehner, J W Olivier Van Till, Jos G A Houbiers, Reynaldo V Martina, Dirk P Cerneus, Joost H J M Melis, Antoni Majek, Egils Vjaters, Michael Urban, Henrikas Ramonas, Daniel A Shoskes, J Curtis Nickel

Clinic for Urology, Pediatric Urology and Andrology, Justus-Liebig-University, Giessen, Germany., Astellas Pharma Europe B.V., Leiden, The Netherlands. Electronic address: ., Astellas Pharma Europe B.V., Leiden, The Netherlands., Department of Health Sciences, College of Medicine, Biological Sciences and Psychology, University of Leicester, United Kingdom., Centrum Medyczne Szpital Sw Rodziny Sp z o.o. Lodz, Poland., Stradins Clinical University Hospital, Riga, Latvia., Androgeos, Praha 6, Czech Republic., Vilnius University Hospital "Santariskiu Klinikos" Urology Centre, Vilnius, Lithuania., Glickman Urological and Kidney Institute, Cleveland Clinic Foundation, Cleveland, Ohio, United States of America., Department of Urology, Queen's University, Kingston, Ontario, Canada.