An adaptive randomized clinical trial in interstitial cystitis/bladder pain syndrome evaluating efficacy of ASP3652 and the relationship between disease characteristics and Hunner's lesions.

Autor: Houbiers JGA; Astellas Pharma Europe B.V, Leiden, The Netherlands., van Till JWO; Astellas Pharma Europe B.V, Leiden, The Netherlands. olivier.vantill@astellas.com.; Astellas Pharma Inc, Medical & Development, Medical Specialties Therapeutic Area. 2-5-1, Nihonbashi-Honcho, Chuo-ku, Tokyo, 103-8411, Japan. olivier.vantill@astellas.com., Kaper M; Astellas Pharma Europe B.V, Leiden, The Netherlands., Yavuz Y; Astellas Pharma Europe B.V, Leiden, The Netherlands., Martina RV; Astellas Pharma Europe B.V, Leiden, The Netherlands., Cerneus D; Astellas Pharma Europe B.V, Leiden, The Netherlands., Melis J; Astellas Pharma Europe B.V, Leiden, The Netherlands., Stroosma O; Astellas Pharma Europe B.V, Leiden, The Netherlands., Nickel JC; Department of Urology, Queens University, Kingston, Canada., Hanno PM; Department of Urology, Stanford University, Stanford, CA, USA., Nordling J; Department of Urology, University of Copenhagen, Copenhagen, Denmark.
Jazyk: angličtina
Zdroj: World journal of urology [World J Urol] 2021 Jun; Vol. 39 (6), pp. 2065-2071. Date of Electronic Publication: 2020 Jul 30.
DOI: 10.1007/s00345-020-03372-z
Abstrakt: Purpose: The primary purpose of this study was to evaluate the effect of the fatty acid amide hydrolase (FAAH) inhibitor ASP3652 on efficacy and safety in patients with Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS). The secondary purpose was to evaluate phenotyping based on Hunner's lesions (HL).
Methods: In this randomized trial, adult female patients with moderate/severe IC/BPS received 12 weeks of treatment with an oral dose of ASP3652 (50, 150, or 300 mg twice daily) or placebo. A Bayesian model was employed using accumulating data to adjust the randomization probability and to analyze the primary efficacy variable (change from baseline to end of treatment in Mean Daily Pain [MDP; range 0-10]). Study outcomes and patient characteristics of patients with and without HL (HL+ and HL-) were compared.
Results: In total, 287 patients were randomized. The 300 mg dose group (n = 97) showed the largest effect, i.e., a mean change from baseline to end of treatment of -1.73 in MDP. However, the mean difference from placebo was 0.02. The probability that this dose was better than placebo was 13.5%. Adverse event incidence was low and similar between study groups. HL+ patients were older and had more severe symptoms than HL-. An association was suggested in HL+ patients between changes in micturition frequency and MDP (R = 0.41 [95% CI 0.18, 0.63]), which was not observed in HL- (R = 0.04 [95% CI -0.16, 0.29]).
Conclusion: ASP3652 was safe and well tolerated, but did not show efficacy in IC/BPS. The observed differences between HL+ and HL- suggest that IC/BPS diagnosis and treatment may be approached differently in these two phenotypes.
Trial Registration: EudraCT number 2011-004555-39, date of registration: 2012-05-07.
Databáze: MEDLINE
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