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A randomised double-blind placebo-controlled phase II study of AGI004 for control of chemotherapy-induced diarrhoea

BACKGROUND: AGI004 is a controlled-release transdermal patch preparation of mecamylamine. We conducted a randomised placebo-controlled phase II study of two dose levels of AGI004 in chemotherapy-induced diarrhoea (CID). METHODS: Adult patients receiving chemotherapy who had experienced diarrhoea (NC...

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Autores principales: Coyle, V M, Lungulescu, D, Toganel, C, Niculescu, A, Pop, S, Ciuleanu, T, Cebotaru, C, Devane, J, Martin, M, Wilson, R H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3619064/
https://www.ncbi.nlm.nih.gov/pubmed/23462724
http://dx.doi.org/10.1038/bjc.2013.35
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author Coyle, V M
Lungulescu, D
Toganel, C
Niculescu, A
Pop, S
Ciuleanu, T
Cebotaru, C
Devane, J
Martin, M
Wilson, R H
author_facet Coyle, V M
Lungulescu, D
Toganel, C
Niculescu, A
Pop, S
Ciuleanu, T
Cebotaru, C
Devane, J
Martin, M
Wilson, R H
author_sort Coyle, V M
collection PubMed
description BACKGROUND: AGI004 is a controlled-release transdermal patch preparation of mecamylamine. We conducted a randomised placebo-controlled phase II study of two dose levels of AGI004 in chemotherapy-induced diarrhoea (CID). METHODS: Adult patients receiving chemotherapy who had experienced diarrhoea (NCI grade 1–2) during previous cycles of chemotherapy were eligible. In all, 64 patients were randomised to receive AGI004 4 mg then 8 mg per 24 h transdermal patch or placebo for two sequential cycles of chemotherapy. Patients' severity of diarrhoea was physician-assessed using NCI grade of diarrhoea and patient-assessed using information recorded in daily diaries of bowel movements. RESULTS: Overall AGI004 doubled the odds of a response to treatment on the first day of chemotherapy based on physician assessment of NCI grade of diarrhoea compared with placebo (odds ratio=2.0, 90% confidence interval: 0.9–4.5) and there was a trend to improved response rates for AGI004 for the full treatment cycle although these results were not statistically significant. There was also evidence of significantly improved response rates based on patient assessment of diarrhoea both overall (P=0.05) and at the 8-mg dose level (P=0.02) compared with placebo. CONCLUSION: AGI004 demonstrated effectiveness in reducing chemotherapy-associated diarrhoea, with results suggesting response across multiple measurements of diarrhoea. Treatment was well tolerated with no drug-related adverse events. Further evaluation of this agent in the management of CID is warranted.
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spelling pubmed-36190642014-03-19 A randomised double-blind placebo-controlled phase II study of AGI004 for control of chemotherapy-induced diarrhoea Coyle, V M Lungulescu, D Toganel, C Niculescu, A Pop, S Ciuleanu, T Cebotaru, C Devane, J Martin, M Wilson, R H Br J Cancer Clinical Study BACKGROUND: AGI004 is a controlled-release transdermal patch preparation of mecamylamine. We conducted a randomised placebo-controlled phase II study of two dose levels of AGI004 in chemotherapy-induced diarrhoea (CID). METHODS: Adult patients receiving chemotherapy who had experienced diarrhoea (NCI grade 1–2) during previous cycles of chemotherapy were eligible. In all, 64 patients were randomised to receive AGI004 4 mg then 8 mg per 24 h transdermal patch or placebo for two sequential cycles of chemotherapy. Patients' severity of diarrhoea was physician-assessed using NCI grade of diarrhoea and patient-assessed using information recorded in daily diaries of bowel movements. RESULTS: Overall AGI004 doubled the odds of a response to treatment on the first day of chemotherapy based on physician assessment of NCI grade of diarrhoea compared with placebo (odds ratio=2.0, 90% confidence interval: 0.9–4.5) and there was a trend to improved response rates for AGI004 for the full treatment cycle although these results were not statistically significant. There was also evidence of significantly improved response rates based on patient assessment of diarrhoea both overall (P=0.05) and at the 8-mg dose level (P=0.02) compared with placebo. CONCLUSION: AGI004 demonstrated effectiveness in reducing chemotherapy-associated diarrhoea, with results suggesting response across multiple measurements of diarrhoea. Treatment was well tolerated with no drug-related adverse events. Further evaluation of this agent in the management of CID is warranted. Nature Publishing Group 2013-03-19 2013-03-05 /pmc/articles/PMC3619064/ /pubmed/23462724 http://dx.doi.org/10.1038/bjc.2013.35 Text en Copyright © 2013 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/3.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Clinical Study
Coyle, V M
Lungulescu, D
Toganel, C
Niculescu, A
Pop, S
Ciuleanu, T
Cebotaru, C
Devane, J
Martin, M
Wilson, R H
A randomised double-blind placebo-controlled phase II study of AGI004 for control of chemotherapy-induced diarrhoea
title A randomised double-blind placebo-controlled phase II study of AGI004 for control of chemotherapy-induced diarrhoea
title_full A randomised double-blind placebo-controlled phase II study of AGI004 for control of chemotherapy-induced diarrhoea
title_fullStr A randomised double-blind placebo-controlled phase II study of AGI004 for control of chemotherapy-induced diarrhoea
title_full_unstemmed A randomised double-blind placebo-controlled phase II study of AGI004 for control of chemotherapy-induced diarrhoea
title_short A randomised double-blind placebo-controlled phase II study of AGI004 for control of chemotherapy-induced diarrhoea
title_sort randomised double-blind placebo-controlled phase ii study of agi004 for control of chemotherapy-induced diarrhoea
topic Clinical Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3619064/
https://www.ncbi.nlm.nih.gov/pubmed/23462724
http://dx.doi.org/10.1038/bjc.2013.35
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