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[O2–09–06]: EVIDENCE THAT ORAL P38 MAPK ALPHA ANTAGONISM IMPROVES EPISODIC MEMORY IN PATIENTS WITH EARLY ALZHEIMER's DISEASE (AD)
Author(s) -
Prins Niels D.,
Alam John,
Chu HuiMay,
Scheltens Philip
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.07.197
Subject(s) - episodic memory , recall , verbal memory , medicine , hippocampus , wechsler memory scale , memory impairment , audiology , psychology , wechsler adult intelligence scale , cognition , psychiatry , cognitive psychology
single dose and 275 mg QD. The dose escalation stopped after predefined exposure limits were reached so maximum tolerated dose was not achieved. No SAE and severe AEs were reported. Most AEs reported were mild in severity. The PF-06751979 plasma PK was consistent after single and multiple doses with median Tmax w4 hours and the mean terminal half-life of 30-40 hours. Steady state was achieved by 7 days with 2-2.5 fold accumulation. PK was comparable between young and older subjects as well as between Japanese and non-Japanese subjects. Significant plasma and CSF Ab reduction was seen at all doses compared to placebo. The steady state levels of CSFAb1-42 were reduced by 69%, 84%, and 93% for the 50 mg, 125 mg, and 275 mg dose groups, respectively. Ab1-40 reductions were comparable to Ab1-42. Conclusions: PF-06751979 is safe and well-tolerated following single and multiple doses in healthy young and older subjects, and potently inhibits Ab in the periphery and CSF.