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.

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.

• Authors: 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
• Journal: Urology (Urology) Vol. 103 Pg. 191-197 (May 2017) ISSN: 1527-9995 [Electronic] United States
• PMID: 28254462 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Enzyme Inhibitors
• Amidohydrolases
• fatty-acid amide hydrolase

Topics

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