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P4‐004: Planning Dose Escalation in Phase III Clinical Trials May Prevent Underpowered Trials and Mitigate the Increase in Sample Size or Duration of Adaptive Trials
Author(s) -
Wang Guoqiao,
McDade Eric,
Bateman Randall,
Hassenstab Jason,
Farlow Martin R.,
Salloway Stephen,
Kennedy Richard E.,
Schneider Lon S.,
Berry Scott,
Xiong Chengjie
Publication year - 2016
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.2016.06.2093
Subject(s) - repeated measures design , sample size determination , clinical trial , duration (music) , medicine , statistics , adaptive design , analysis of variance , categorical variable , psychology , mathematics , art , literature
well as pain and weight loss, in patients with moderate-to-severe AD. Methods: This will be a double-blind, crossover randomized placebo controlled trial (RCT) comparing 6 weeks of nabilone to 6 weeks of placebo, with a 1-week washout preceding each treatment phase. Eligible patients with moderate-to-severe AD and clinically significant agitation will be randomized to receive either nabilone (.5 – 2 mg) or placebo (1:1 ratio) for 6 weeks each. The recruitment goal is to randomize 40 patients over 2 years. The primary outcome will be agitation, as measured by the Cohen-Mansfield Agitation Inventory. The secondary outcomes will include overall behaviour, cognition and global impression. Exploratory outcomes include pain, nutritional status, safety and biomarkers of oxidative/nitrosative stress, inflammation and cholesterol metabolism. Results:This crossover RCT will establish the therapeutic relevance of nabilone in the treatment of AD by examining its efficacy in the treatment of agitation, pain and weight, while collecting double-blind information on safety. Conclusions: If positive, the findings of this study will provide rationale for the feasibility of a larger, multicentre trial. Additionally, a safe and efficacious pharmacological intervention for agitation, pain and weight loss in patients with moderate-to-severe AD could increase quality-of-life, reduce caregiver stress and avoid unnecessary institutionalization and related increases in health care costs.