Phase II Crossover Trial of Varenicline in Mild-to-Moderate Alzheimer's Disease

被引:31
作者
Kim, Seong Yoon [1 ]
Choi, Seong Hye [2 ]
Rollema, Hans [3 ]
Schwam, Elias M. [4 ]
McRae, Tom [4 ]
Dubrava, Sarah [4 ]
Jacobsen, Janice [4 ]
机构
[1] Asan Med Ctr, Dept Psychiat, Seoul 138736, South Korea
[2] Inha Univ, Sch Med, Dept Neurol, Inchon, South Korea
[3] Rollema Biomed Consulting, Mystic, CT USA
[4] Pfizer Inc, Groton, CT 06340 USA
关键词
Alzheimer's disease; Cognition; Crossover study; Partial agonist; Receptor activation; Varenicline; RECEPTOR PARTIAL AGONIST; NEURONAL NICOTINIC RECEPTORS; SUSTAINED-RELEASE BUPROPION; ACETYLCHOLINE-RECEPTOR; SMOKING-CESSATION; DOUBLE-BLIND; GENETIC VARIANT; TC-1734; AZD3480; PHARMACOKINETICS; COGNITION;
D O I
10.1159/000355373
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Background: Evidence supports a role of a4 beta 2 receptors in Alzheimer's disease (AD). Methods: This Korean, multicenter, double-blind, two-period (6 weeks each), crossover study randomized participants to the order in which they received varenicline (1 mg twice daily) and placebo. Assessments included AD Assessment Scale-Cognitive Subscale (ADAS-Cog) 75, Neuropsychiatric Inventory (NPI), adverse events (AEs) and Columbia-Suicide Severity Rating Scale (C-SSRS). Results: For varenicline versus placebo (n = 66 randomized), there was no significant difference in the week 6 least square (LS) mean ADAS-Cog 75 total score (primary endpoint; 18.07 vs. 18.49; p = 0.3873) and a slight worsening in the week 6 LS mean NPI (3.82 vs. 2.55; p = 0.0468), primarily driven by decreased appetite/eating. Common treatment-related AEs were nausea (23.3; 3.4%), vomiting (15.0%; 0) and decreased appetite (15.0; 6.8%). Conclusions: Varenicline did not improve cognition, behavior or global change in this population. The most frequent varenicline-associated AEs were gastrointestinal; psychiatric AEs were rare and similar between the groups. (c) 2013 S. Karger AG, Basel
引用
收藏
页码:232 / 245
页数:14
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