Abstract :
Objectives: Tramiprosate (homotaurine, ALZHEMEDTM) was recently investigated for its efficacy,
safety and disease-modification effects in a Phase III clinical study in mild to moderate Alzheimer’s disease (AD)
patients (the Alphase study). The primary cognitive endpoint measure of that study was the Alzheimer’s Disease
Assessment Scale-cognitive subscale (ADAS-cog). To characterize potential cognitive benefits of tramiprosate,
the present study describes exploratory analyses performed on scores obtained from the specific ADAS-cog
subscales in order to determine whether specific domains of cognition may be differentially affected by
tramiprosate, which would not have been evident from the measure’s total score. Design: Multi-center, doubleblind,
randomized, placebo-controlled study. Setting: 67 investigative sites in the United States and Canada.
Participants: A total of 1,052 patients were randomized. Interventions: Patients were randomized to receive
twice a day Placebo (n=353), tramiprosate 100 mg (n=352) and tramiprosate 150 mg (n=347). Measurements:
ADAS-cog assessments were conducted every three months over the 78-week study period. Exploratory analyses
were performed by comparing ADAS-cog subscale scores between Placebo and each active treatment arm at each
visit. Results: The findings of this analysis revealed statistically significant differences or statistical trends in
favour of tramiprosate on six ADAS-cog subscales, namely Following Commands, Language Comprehension,
Ideational Praxis, Object Naming, Remembering Test Instructions, and Spoken Language Ability. Differences in
favor of Placebo were only observed on the Constructional Praxis subscale. Conclusion: This exploratory
analysis suggests that tramiprosate may have some benefit on memory, language and praxis skills in mild to
moderate AD individuals. Future clinical studies of tramiprosate should include specialized neuropsychological
tests to validate its effects within these cognitive domains.
