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Effect of Concurrent Use of Memantine on the Efficacy of Masupirdine (SUVN-502): A Post Hoc Analysis of a Phase 2 Randomized Placebo-Controlled Study
INTRODUCTION: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive deterioration in cognition, memory and activities of daily living. Selective blockade of serotonin-6 (5-HT(6)) receptors, which are exclusively localized to the central nervous system, is reported to...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Healthcare
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9588135/ https://www.ncbi.nlm.nih.gov/pubmed/35908254 http://dx.doi.org/10.1007/s40120-022-00390-4 |
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author | Nirogi, Ramakrishna Goyal, Vinod Kumar Benade, Vijay Subramanian, Ramkumar Ravula, Jyothsna Jetta, Satish Shinde, Anil Pandey, Santosh Kumar Jayarajan, Pradeep Jasti, Venkat Cummings, Jeffrey |
author_facet | Nirogi, Ramakrishna Goyal, Vinod Kumar Benade, Vijay Subramanian, Ramkumar Ravula, Jyothsna Jetta, Satish Shinde, Anil Pandey, Santosh Kumar Jayarajan, Pradeep Jasti, Venkat Cummings, Jeffrey |
author_sort | Nirogi, Ramakrishna |
collection | PubMed |
description | INTRODUCTION: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive deterioration in cognition, memory and activities of daily living. Selective blockade of serotonin-6 (5-HT(6)) receptors, which are exclusively localized to the central nervous system, is reported to play an important role in learning and memory. Masupirdine is a potent and selective 5-HT(6) receptor antagonist with pro-cognitive properties in animal models of cognition. METHODS: The efficacy and safety of masupirdine were evaluated in patients with moderate AD concurrently treated with donepezil and memantine. A total of 564 patients were randomized in a 1:1:1 ratio. The study consisted of a 26-week double-blind treatment period. The primary efficacy outcome was the 11-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-Cog 11). Changes from baseline were analyzed using a mixed effects model for repeated measures (MMRM). In exploratory post hoc analyses, patients were subdivided based on the use of memantine dosage forms and memantine plasma concentrations, to evaluate the impact of memantine on the efficacy of masupirdine. RESULTS: In an exploratory post hoc analysis, less worsening in cognition (ADAS-Cog 11 scores) was observed with masupirdine treatment as compared with placebo in patients whose trough memantine plasma concentrations were ≤ 100 ng/mL. CONCLUSIONS: Although prespecified study endpoints of the phase 2 study were not met, these exploratory post hoc subgroup observations are hypothesis-generating and suggest that the efficacy of masupirdine was adversely affected by concurrent therapy with memantine. Further assessment of masupirdine to determine its potential role as a treatment option for cognitive deficits associated with AD is warranted. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (NCT02580305). |
format | Online Article Text |
id | pubmed-9588135 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer Healthcare |
record_format | MEDLINE/PubMed |
spelling | pubmed-95881352022-11-29 Effect of Concurrent Use of Memantine on the Efficacy of Masupirdine (SUVN-502): A Post Hoc Analysis of a Phase 2 Randomized Placebo-Controlled Study Nirogi, Ramakrishna Goyal, Vinod Kumar Benade, Vijay Subramanian, Ramkumar Ravula, Jyothsna Jetta, Satish Shinde, Anil Pandey, Santosh Kumar Jayarajan, Pradeep Jasti, Venkat Cummings, Jeffrey Neurol Ther Original Research INTRODUCTION: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive deterioration in cognition, memory and activities of daily living. Selective blockade of serotonin-6 (5-HT(6)) receptors, which are exclusively localized to the central nervous system, is reported to play an important role in learning and memory. Masupirdine is a potent and selective 5-HT(6) receptor antagonist with pro-cognitive properties in animal models of cognition. METHODS: The efficacy and safety of masupirdine were evaluated in patients with moderate AD concurrently treated with donepezil and memantine. A total of 564 patients were randomized in a 1:1:1 ratio. The study consisted of a 26-week double-blind treatment period. The primary efficacy outcome was the 11-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-Cog 11). Changes from baseline were analyzed using a mixed effects model for repeated measures (MMRM). In exploratory post hoc analyses, patients were subdivided based on the use of memantine dosage forms and memantine plasma concentrations, to evaluate the impact of memantine on the efficacy of masupirdine. RESULTS: In an exploratory post hoc analysis, less worsening in cognition (ADAS-Cog 11 scores) was observed with masupirdine treatment as compared with placebo in patients whose trough memantine plasma concentrations were ≤ 100 ng/mL. CONCLUSIONS: Although prespecified study endpoints of the phase 2 study were not met, these exploratory post hoc subgroup observations are hypothesis-generating and suggest that the efficacy of masupirdine was adversely affected by concurrent therapy with memantine. Further assessment of masupirdine to determine its potential role as a treatment option for cognitive deficits associated with AD is warranted. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (NCT02580305). Springer Healthcare 2022-07-31 /pmc/articles/PMC9588135/ /pubmed/35908254 http://dx.doi.org/10.1007/s40120-022-00390-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by-nc/4.0/Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Original Research Nirogi, Ramakrishna Goyal, Vinod Kumar Benade, Vijay Subramanian, Ramkumar Ravula, Jyothsna Jetta, Satish Shinde, Anil Pandey, Santosh Kumar Jayarajan, Pradeep Jasti, Venkat Cummings, Jeffrey Effect of Concurrent Use of Memantine on the Efficacy of Masupirdine (SUVN-502): A Post Hoc Analysis of a Phase 2 Randomized Placebo-Controlled Study |
title | Effect of Concurrent Use of Memantine on the Efficacy of Masupirdine (SUVN-502): A Post Hoc Analysis of a Phase 2 Randomized Placebo-Controlled Study |
title_full | Effect of Concurrent Use of Memantine on the Efficacy of Masupirdine (SUVN-502): A Post Hoc Analysis of a Phase 2 Randomized Placebo-Controlled Study |
title_fullStr | Effect of Concurrent Use of Memantine on the Efficacy of Masupirdine (SUVN-502): A Post Hoc Analysis of a Phase 2 Randomized Placebo-Controlled Study |
title_full_unstemmed | Effect of Concurrent Use of Memantine on the Efficacy of Masupirdine (SUVN-502): A Post Hoc Analysis of a Phase 2 Randomized Placebo-Controlled Study |
title_short | Effect of Concurrent Use of Memantine on the Efficacy of Masupirdine (SUVN-502): A Post Hoc Analysis of a Phase 2 Randomized Placebo-Controlled Study |
title_sort | effect of concurrent use of memantine on the efficacy of masupirdine (suvn-502): a post hoc analysis of a phase 2 randomized placebo-controlled study |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9588135/ https://www.ncbi.nlm.nih.gov/pubmed/35908254 http://dx.doi.org/10.1007/s40120-022-00390-4 |
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