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


Wagenlehner, Florian, van Till, JW Olivier, Houbiers, Jos GA, Martina, RV ORCID: 0000-0002-1925-820X, Cerneus, Dirk P, Melis, Joost HJM, Majek, Antoni, Vjaters, Egils, Urban, Michael, Ramonas, Henrikas et al (show 2 more authors) (2017) Fatty Acid Amide Hydrolase Inhibitor Treatment in Men With Chronic Prostatitis/Chronic Pelvic Pain Syndrome: An Adaptive Double-blind, Randomized Controlled Trial. Urology, 103. pp. 191-197.

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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. 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.

Item Type: Article
Uncontrolled Keywords: Humans, Prostatitis, Pelvic Pain, Amidohydrolases, Enzyme Inhibitors, Drug Monitoring, Treatment Outcome, Double-Blind Method, Biological Availability, Dose-Response Relationship, Drug, Adult, Middle Aged, Male, Lower Urinary Tract Symptoms
Depositing User: Symplectic Admin
Date Deposited: 24 Sep 2018 10:37
Last Modified: 19 Jan 2023 06:58
DOI: 10.1016/j.urology.2017.02.029
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3008613
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