AD PD 2015 Victor Villemagne's Abstract

Objectives: The trial aimed to explore putative imaging markers to help inform future clinical trial design of PBT2 in Alzheimer’s disease (AD).
Methods: We conducted a 52-week double-blind, randomized , placebo controlled trial involving 42 patients with mild AD (71.1+/-9.2 years, MMSE 24.2+/-2.5) with a baseline C-PiB-SUVR≥1.7. Participants received either PBT2 (250 mg/day) or placebo for 52 weeks. Primary outcome measure was Aβ burden as measured by C-PiB-PET at baseline and 12 months. Participants also underwent periodic neuropsychological evaluation, FDG-PET and MRI scans.
Results: PBT2 was well tolerated. At baseline, there were no significant between-group differences in age, gender, ApoE, hippocampal volume, PiB or FDG SUVR. Baseline C-PiB SUVR ranged between 1.73 and 3.31 (median 2.5). Despite PBT2-treated patients showing a significant decrease in Aβ burden at 12 months (-2.5%, p=.048) post-hoc, this was accompanied by a similar decrease in the placebo group (-3.1%, p=0.06), yielding no significant between-group differences. Similarly, no significant between-group differences were found on cognition, FDG or MRI volumetrics, though a trend towards a slower rate of hippocampal atrophy on the PBT2-treated patients (p=0.09) was observed. When analyzed separately, PBT2-treated participants with baseline >2.5 SUVR (n=11) showed significant reductions in PiB-SUVR (p=0.002) while those with Conclusions: There were no between-group differences in Aβ burden in PBT2 treated and untreaded mild AD patients, despite a significant reduction in Aβ in the PBT2-treated patients, especially in those with a baseline PiB-SUVR ≥2.5.