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.
Endocannabinoids
Fatty acid amide hydrolase (FAAH) inhibitor
Hunner’s lesion
Interstitial cystitis
Patient characteristics
Phenotype
Journal
World journal of urology
ISSN: 1433-8726
Titre abrégé: World J Urol
Pays: Germany
ID NLM: 8307716
Informations de publication
Date de publication:
Jun 2021
Jun 2021
Historique:
received:
27
04
2020
accepted:
16
07
2020
pubmed:
1
8
2020
medline:
9
10
2021
entrez:
1
8
2020
Statut:
ppublish
Résumé
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). 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. 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]). 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. EudraCT number 2011-004555-39, date of registration: 2012-05-07.
Identifiants
pubmed: 32734461
doi: 10.1007/s00345-020-03372-z
pii: 10.1007/s00345-020-03372-z
doi:
Substances chimiques
ASP3652
0
Organic Chemicals
0
Amidohydrolases
EC 3.5.-
fatty-acid amide hydrolase
EC 3.5.1.-
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
2065-2071Commentaires et corrections
Type : CommentIn
Type : CommentIn
Références
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