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Aisen PS, Gauthier S, Ferris SH, et al. Tramiprosate in mild-to-moderate Alzheimer's disease - a randomized, double-blind, placebo-controlled, multi-centre study (the Alphase Study). Arch Med Sci. 2011;7(1):102-11doi: 10.5114/aoms.2011.20612.
Aisen, P. S., Gauthier, S., Ferris, S. H., Saumier, D., Haine, D., Garceau, D., Duong, A., Suhy, J., Oh, J., Lau, W. C., & Sampalis, J. (2011). Tramiprosate in mild-to-moderate Alzheimer's disease - a randomized, double-blind, placebo-controlled, multi-centre study (the Alphase Study). Archives of medical science : AMS, 7(1), 102-11. https://doi.org/10.5114/aoms.2011.20612
Aisen, Paul S, et al. "Tramiprosate in mild-to-moderate Alzheimer's disease - a randomized, double-blind, placebo-controlled, multi-centre study (the Alphase Study)." Archives of medical science : AMS vol. 7,1 (2011): 102-11. doi: https://doi.org/10.5114/aoms.2011.20612
Aisen PS, Gauthier S, Ferris SH, Saumier D, Haine D, Garceau D, Duong A, Suhy J, Oh J, Lau WC, Sampalis J. Tramiprosate in mild-to-moderate Alzheimer's disease - a randomized, double-blind, placebo-controlled, multi-centre study (the Alphase Study). Arch Med Sci. 2011 Feb;7(1):102-11. doi: 10.5114/aoms.2011.20612. Epub 2011 Mar 08. PMID: 22291741; PMCID: PMC3258678.
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Arch Med Sci. 2011 Feb;7(1):102-11. doi: 10.5114/aoms.2011.20612. Epub 2011 Mar 08.

Tramiprosate in mild-to-moderate Alzheimer's disease - a randomized, double-blind, placebo-controlled, multi-centre study (the Alphase Study).

Archives of medical science : AMS

Paul S Aisen, Serge Gauthier, Steven H Ferris, Daniel Saumier, Denis Haine, Denis Garceau, Anh Duong, Joyce Suhy, Joonmi Oh, Wan C Lau, John Sampalis

Affiliations

  1. University of California, San Diego, La Jolla, CA, USA.

PMID: 22291741 PMCID: PMC3258678 DOI: 10.5114/aoms.2011.20612

Abstract

INTRODUCTION: The aim of the study was to assess the clinical efficacy, safety, and disease-modification effects of tramiprosate (homotaurine, ALZHEMED(TM)) in mild-to-moderate Alzheimer's disease (AD).

MATERIAL AND METHODS: Double-blind, placebo-controlled, randomized trial in 67 clinical centres across North America. Patients aged ≥ 50 years, with mild-to-moderate AD (Mini-Mental State Examination score between 16 and 26) and on stable doses of cholinesterase inhibitors, alone or with memantine.

INTERVENTION: 78-week treatment with placebo, tramiprosate 100 mg or tramiprosate 150 mg BID.

MEASUREMENTS: Alzheimer Disease Assessment Scale - cognitive subscale (ADAS-cog) and Clinical Dementia Rating - Sum of Boxes (CDR-SB) assessments were performed at baseline and every 13 weeks. Baseline and 78-week magnetic resonance imaging (MRI) hippocampus volume (HV) measurements were conducted in a subgroup of patients.

RESULTS: A total of 1,052 patients were enrolled and 790 (75.1%) completed the 78-week trial. Patient discontinuation and reasons for withdrawal were similar across groups. Planned analyses did not reveal statistically significant between-group differences. Lack of adequate statistical validity of the planned analysis models led to the development of revised predictive models. These adjusted models showed a trend toward a treatment effect for ADAS-cog (P = 0.098) and indicated significantly less HV loss for tramiprosate 100 mg (P = 0.035) and 150 mg (P = 0.009) compared to placebo. The incidence of adverse events was similar across treatment groups.

CONCLUSIONS: The primary planned analyses did not show a significant treatment effect, but were confounded by unexplained variance. Post-hoc analyses showed a significant treatment-related reduction in HV loss. However, there was only a trend towards slowing of decline on the ADAS-cog and no slowing of decline on the CDR-SB. These results must be interpreted in consideration of the limitations of clinical and disease-modification outcome measures and their relationship, the heterogeneity of the disease and the impact of confounding demographic and clinical variables.

Keywords: Alzheimer’s disease; amyloid; disease-modification; tramiprosate; volumetric MRI

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