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30.07.2020 | Original Article

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

verfasst von: Jos G. A. Houbiers, J. W. Olivier van Till, Mathilde Kaper, Yalcin Yavuz, Reynaldo V. Martina, Dirk Cerneus, Joost Melis, Otto Stroosma, J. Curtis Nickel, Phil M. Hanno, Jørgen Nordling

Erschienen in: World Journal of Urology | Ausgabe 6/2021

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Abstract

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.

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Titel: 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
verfasst von: Jos G. A. Houbiers
J. W. Olivier van Till
Mathilde Kaper
Yalcin Yavuz
Reynaldo V. Martina
Dirk Cerneus
Joost Melis
Otto Stroosma
J. Curtis Nickel
Phil M. Hanno
Jørgen Nordling
Publikationsdatum: 30.07.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: World Journal of Urology / Ausgabe 6/2021
Print ISSN: 0724-4983
Elektronische ISSN: 1433-8726
DOI: https://doi.org/10.1007/s00345-020-03372-z

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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