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


Burstein, Aaron H, Grimes, Imogene, Galasko, Douglas R, Aisen, Paul S, Sabbagh, Marwan, Mjalli, Adnan MM


BMC Neurology, Volume: 14, Pages.: 12-12

Year of Publication



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 5 mg/day dose of TTP488. Acute, reversible cognitive worsening was seen with a 20 mg/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 (60 mg for 6 days followed by 20 mg/day; 15 mg for 6 days followed by 5 mg/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 5 mg/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 5 mg/day on ADAS-cog and trends on CDR-sb and ADCS-ADL at Month 18. TTP488 plasma concentrations of 7.6-16.8 ng/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 46.8-167.0 ng/mL.; Conclusions: Results of these analyses support further investigation of 5 mg/day in future Phase 3 trials in patients with mild AD.;

Bibtex Citation

@article{Burstein_2014, doi = {10.1186/1471-2377-14-12}, url = {}, year = 2014, publisher = {Springer Nature}, volume = {14}, number = {1}, pages = {12}, author = {Aaron H Burstein and Imogene Grimes and Douglas R Galasko and Paul S Aisen and Marwan Sabbagh and Adnan MM Mjalli}, title = {Effect of {TTP}488 in patients with mild to moderate Alzheimer's disease}, journal = {{BMC} Neurology} }


aged, alzheimer disease, antagonists inhibitors, antigens neoplasm, double-blind method, drug therapy, female, humans, male, mitogenactivated protein kinases, neuroprotective agents, therapeutic use

Countries of Study


Types of Dementia

Alzheimer’s Disease

Types of Study

Randomised Controlled Trial

Type of Outcomes


Type of Interventions

Pharmaceutical Interventions

Pharmaceutical Interventions