Effect of Tarenflurbil on Cognitive Decline and Activities of Daily Living in Patients With Mild Alzheimer Disease
By R. Green, Lon S. Schneider, D. Amato, A. Beelen, G. Wilcock, E. Swabb, K. Zavitz. Journal of the American Medical Association (JAMA), 2009
627 citations recorded by the source corpus.
Context Amyloid-β peptide (Aβ42) has been implicated in the pathogenesis of Alzheimer disease (AD). Tarenflurbil, a selective Aβ42-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. Design, Setting, and Patients 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. Intervention Tarenflurbil, 800 mg, or placebo, administered twice a day. Main Outcome Measures 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. Conclusion Tarenflurbil did not slow cognitive decline or the loss of activities of daily living in patients with mild AD.
Subfields: Neurology, Pharmacology, Physiology
View Paper: https://www.semanticscholar.org/paper/15f388350e5672324389cdb7fbef516692b56612
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Citations in the corpus
- Cognitive frailty: Rational and definition from an (I.A.N.A./I.A.G.G.) International Consensus Group (2013, neutral): “Moreover, several promising new drugs based mainly on the amyloid hypothesis have recently failed to alter established disease in phase 3 clinical trials (5).”
- The Alzheimer's Disease-Associated Amyloid β-Protein Is an Antimicrobial Peptide (2010, neutral): “More recently, in a clinical trial of the Ab42- lowering agent tarenflurbil patients receiving the drug have significantly increased rates of infection [34].”
- Inflammation in Alzheimer disease-a brief review of the basic science and clinical literature. (2012, background): “A large-scale treatment trial with an enantiomer of flurbiprofen, for example, is often lumped into summaries of the negative results of anti-inflammatory drug treatment despite the fact that, by design, the enantiomer had little to no anti-inflammatory activity (Green et al. 2009).”