Domain-specific cognitive effects of tramiprosate in patients with mild to moderate Alzheimer's disease: ADAS-cog subscale results from the Alphase Study.
OBJECTIVE
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.


METHODS
Multi-center, double-blind, randomized, placebo-controlled study.


METHODS
67 investigative sites in the United States and Canada.


METHODS
A total of 1,052 patients were randomized.


METHODS
Patients were randomized to receive twice a day Placebo (n=353), tramiprosate 100 mg (n=352) and tramiprosate 150 mg (n=347).


METHODS
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.


CONCLUSIONS
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.
Saumier
D
D
Department of Neurology and Neurosurgery, McGill University, Montreal, Canada.
Duong
A
A
Haine
D
D
Garceau
D
D
Sampalis
J
J
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D000704:Analysis of Variance; D003071:Cognition / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D018755:GABA Agonists / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013654:Taurine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
D018755:GABA Agonists; D018696:Neuroprotective Agents; D013654:Taurine; C001355:tramiprosate