Effect of tarenflurbil on cognitive decline and activities of daily living in patients with mild Alzheimer disease: a randomized controlled trial.
BACKGROUND
Amyloid-beta peptide (Abeta(42)) has been implicated in the pathogenesis of Alzheimer disease (AD). Tarenflurbil, a selective Abeta(42)-lowering agent, demonstrated encouraging results on cognitive and functional outcomes among mildly affected patients in an earlier phase 2 trial.


OBJECTIVE
To determine the efficacy, safety, and tolerability of tarenflurbil.


METHODS
A multicenter, randomized, double-blind, placebo-controlled trial enrolling patients with mild AD was conducted at 133 trial sites in the United States between February 21, 2005, and April 30, 2008. Concomitant treatment with cholinesterase inhibitors or memantine was permitted.


METHODS
Tarenflurbil, 800 mg, or placebo, administered twice a day.


METHODS
Co-primary efficacy end points were the change from baseline to month 18 in total score on the subscale of the Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog, 80-point version) and Alzheimer Disease Cooperative Studies-activities of daily living (ADCS-ADL) scale. Additional prespecified slope analyses explored the possibility of disease modification.


RESULTS
Of the 1684 participants randomized, 1649 were included in the analysis, and 1046 completed the trial. Tarenflurbil had no beneficial effect on the co-primary outcomes (difference in change from baseline to month 18 vs placebo, based on least squares means: 0.1 for ADAS-Cog; 95% CI, -0.9 to 1.1; P = .86 and -0.5 for ADCS-ADL; 95% CI, -1.9 to 0.9; P = .48) using an intent-to-treat analysis. No significant differences occurred in the secondary outcomes. The ADAS-Cog score decreased by 7.1 points over 18 months. The tarenflurbil group had a small increase in frequency of dizziness, anemia, and infections.


CONCLUSIONS
Tarenflurbil did not slow cognitive decline or the loss of activities of daily living in patients with mild AD.


BACKGROUND
clinicaltrials.gov Identifier: NCT00105547.
Green
Robert C
RC
Department of Neurology, Boston University School of Medicine, 72 E Concord St, L-320, Boston, MA 02118, USA. rcgreen@bu.edu
Schneider
Lon S
LS
Amato
David A
DA
Beelen
Andrew P
AP
Wilcock
Gordon
G
Swabb
Edward A
EA
Zavitz
Kenton H
KH
D000203:Activities of Daily Living; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D016229:Amyloid beta-Peptides; D003071:Cognition; D003072:Cognition Disorders / Q000188:drug therapy; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005480:Flurbiprofen / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments
D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; C505522:tarenflurbil; D005480:Flurbiprofen; D053829:Amyloid Precursor Protein Secretases