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P1–333: Safety, pharmacokinetics and pharmacodynamics of PQ912, the first glutaminyl cyclase (QC) inhibitor to treat Alzheimer's disease, in healthy elderly
Author(s) -
Black Ronald,
Lues Inge,
Weber Frank,
Meyer Antje,
Hoffman Torsten,
Pokorny Rolf,
Demuth HansUlrich,
Glund Konrad
Publication year - 2013
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.2013.05.559
Subject(s) - pharmacokinetics , medicine , pharmacodynamics , adverse effect , placebo , cohort , pharmacology , pathology , alternative medicine
samples for TTP488 concentrations were collected serially at similar time points as the ADAS-cog. Analyses related TTP concentrations to ADAScog values and changes. Trough concentrations were analyzed for each subject by taking the maximum trough and also by taking the median trough for each subject over time. Subjects were classified into groups according to cutpoints (tertile, quartile, quintile and decile) in the distribution of concentration. Each subject was classified to a single category. Results: Results were generally consistent across various cutpoints evaluated. 5 mg/day and 20 mg/day were associated with mean (95% CI) trough concentrations of 13 (11.7, 14.3) ng/mL and 68.6 (63.5, 73.7) ng/mL, respectively.TTP488 concentrations of 7.6-16.8 ng/mL showed a decreased decline in ADAS-cog over time compared to placebo. Concentrations of 46.8-167.0 ng/mL showed a numerical worsening in ADAS-cog relative to placebo. Conclusions: Analyses suggest that exposure to TTP488 to achieve trough plasma concentrations of 7.6-16.8 ng/mL (i.e. trough concentrations maintained for most subjects who received a 5 mg/day dose) is associated with beneficial effects on ADAS-cog, relative to placebo.