Effect of TTP488 in patients with mild to moderate Alzheimer's disease

Persistent Link:
http://hdl.handle.net/10150/610067
Title:
Effect of TTP488 in patients with mild to moderate Alzheimer's disease
Author:
Burstein, Aaron; Grimes, Imogene; Galasko, Douglas; Aisen, Paul; Sabbagh, Marwan; Mjalli, Adnan
Affiliation:
TransTech Pharma, High Point, NC, USA; Department of Neurosciences, University of California, San Diego, CA, USA; Banner Sun Health Research Institute, Sun City, AZ, USA; University of Arizona, Tucson, Arizona, AZ, USA
Issue Date:
2014
Publisher:
BioMed Central
Citation:
Burstein et al. BMC Neurology 2014, 14:12 http://www.biomedcentral.com/1471-2377/14/12
Journal:
BMC Neurology
Rights:
© 2014 Burstein et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)
Collection Information:
This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.
Abstract:
BACKGROUND:TTP488, an antagonist at the Receptor for Advanced Glycation End products, was evaluated as a potential treatment for patients with mild-to-moderate Alzheimer's disease (AD). A previous report describes decreased decline in ADAS-cog (delta=3.1, p=0.008 at 18 months, ANCOVA with multiple imputation), relative to placebo, following a 5mg/day dose of TTP488. Acute, reversible cognitive worsening was seen with a 20mg/day dose. The present study further evaluates the efficacy of TTP488 by subgroup analyses based on disease severity and concentration effect analysis.METHODS:399 patients were randomized to one of two oral TTP488 doses (60mg for 6 days followed by 20mg/day; 15mg for 6 days followed by 5mg/day) or placebo for 18 months. Pre-specified primary analysis, using an ITT population, was on the ADAS-cog11. Secondary analyses included as a key secondary variable the Clinical Dementia Rating-Sum of Boxes (CDR-SB), and another secondary variable of the ADCS-ADL.RESULTS:On-treatment analysis demonstrated numerical differences favoring 5mg/day over placebo, with nominal significance at Month 18 (delta=2.7, p=0.03). Patients with mild AD, whether defined by MMSE or ADAS-cog, demonstrated significant differences favoring 5mg/day on ADAS-cog and trends on CDR-sb and ADCS-ADL at Month 18. TTP488 plasma concentrations of 7.6-16.8ng/mL were associated with a decreased decline in ADAS-cog over time compared to placebo. Worsening on the ADAS-cog relative to placebo was evident at 46.8-167.0ng/mL.CONCLUSIONS:Results of these analyses support further investigation of 5mg/day in future Phase 3 trials in patients with mild AD.
EISSN:
1471-2377
DOI:
10.1186/1471-2377-14-12
Version:
Final published version
Additional Links:
http://www.biomedcentral.com/1471-2377/14/12

Full metadata record

DC FieldValue Language
dc.contributor.authorBurstein, Aaronen
dc.contributor.authorGrimes, Imogeneen
dc.contributor.authorGalasko, Douglasen
dc.contributor.authorAisen, Paulen
dc.contributor.authorSabbagh, Marwanen
dc.contributor.authorMjalli, Adnanen
dc.date.accessioned2016-05-20T08:57:49Z-
dc.date.available2016-05-20T08:57:49Z-
dc.date.issued2014en
dc.identifier.citationBurstein et al. BMC Neurology 2014, 14:12 http://www.biomedcentral.com/1471-2377/14/12en
dc.identifier.doi10.1186/1471-2377-14-12en
dc.identifier.urihttp://hdl.handle.net/10150/610067-
dc.description.abstractBACKGROUND:TTP488, an antagonist at the Receptor for Advanced Glycation End products, was evaluated as a potential treatment for patients with mild-to-moderate Alzheimer's disease (AD). A previous report describes decreased decline in ADAS-cog (delta=3.1, p=0.008 at 18 months, ANCOVA with multiple imputation), relative to placebo, following a 5mg/day dose of TTP488. Acute, reversible cognitive worsening was seen with a 20mg/day dose. The present study further evaluates the efficacy of TTP488 by subgroup analyses based on disease severity and concentration effect analysis.METHODS:399 patients were randomized to one of two oral TTP488 doses (60mg for 6 days followed by 20mg/dayen
dc.description.abstract15mg for 6 days followed by 5mg/day) or placebo for 18 months. Pre-specified primary analysis, using an ITT population, was on the ADAS-cog11. Secondary analyses included as a key secondary variable the Clinical Dementia Rating-Sum of Boxes (CDR-SB), and another secondary variable of the ADCS-ADL.RESULTS:On-treatment analysis demonstrated numerical differences favoring 5mg/day over placebo, with nominal significance at Month 18 (delta=2.7, p=0.03). Patients with mild AD, whether defined by MMSE or ADAS-cog, demonstrated significant differences favoring 5mg/day on ADAS-cog and trends on CDR-sb and ADCS-ADL at Month 18. TTP488 plasma concentrations of 7.6-16.8ng/mL were associated with a decreased decline in ADAS-cog over time compared to placebo. Worsening on the ADAS-cog relative to placebo was evident at 46.8-167.0ng/mL.CONCLUSIONS:Results of these analyses support further investigation of 5mg/day in future Phase 3 trials in patients with mild AD.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://www.biomedcentral.com/1471-2377/14/12en
dc.rights© 2014 Burstein et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)en
dc.titleEffect of TTP488 in patients with mild to moderate Alzheimer's diseaseen
dc.typeArticleen
dc.identifier.eissn1471-2377en
dc.contributor.departmentTransTech Pharma, High Point, NC, USAen
dc.contributor.departmentDepartment of Neurosciences, University of California, San Diego, CA, USAen
dc.contributor.departmentBanner Sun Health Research Institute, Sun City, AZ, USAen
dc.contributor.departmentUniversity of Arizona, Tucson, Arizona, AZ, USAen
dc.identifier.journalBMC Neurologyen
dc.description.collectioninformationThis item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
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