PDF(Pubmed)
Abstract：
Dynamic balance assessments such as walking adaptability may yield a more realistic prediction of drug-induced falls compared with postural stability measurements, as falls often result from limited gait adjustments when walking. The Interactive Walkway (IWW) measures walking adaptability but sensitivity to medication effects is unknown. If proven sensitive and specific, IWW could serve as a biomarker for targeted fall-risk assessments in early clinical drug development. In this three-way crossover study, 18 healthy elderly (age: 65-80 years) subjects received 5 mg zolpidem, 10 mg suvorexant, or placebo in the morning. Assessments were performed pre-dose and approximately hourly until 9 h post-dose. IWW assessments included an 8-meter walking test, goal-directed stepping, obstacle-avoidance, and tandem-walking. Other pharmacodynamic measurements were the Timed-Up-and-Go (TUG) test at a comfortable and fast pace, adaptive tracking, and body sway. A decline in performance was observed for zolpidem compared with placebo for 3 h post-dose in IWW walking adaptability outcome measures, TUG, adaptive tracking, and body sway. For the IWW tasks, a decrease in walking speed (among others) was observed. IWW parameters were not affected by suvorexant compared with placebo at any timepoint. However, an increase of 9.8% (95%CI: 1.8%, 18.5%) in body sway was observed for suvorexant compared with placebo up to 3 h post-dose. The IWW successfully quantified drug effects of two hypnotic drugs and distinguished between zolpidem and suvorexant regarding their effects on walking. As a biomarker, the IWW demonstrated sensitivity in assessing dynamic balance and potential fall risk in early phase clinical drug development.
摘要：
与姿势稳定性测量相比，诸如步行适应性之类的动态平衡评估可能会对药物引起的跌倒产生更现实的预测。因为跌倒通常是由于行走时步态调整有限。交互式人行道（IWW）可测量步行适应性，但对药物作用的敏感性尚不清楚。如果被证明是敏感和具体的，IWW可以作为早期临床药物开发中针对性跌倒风险评估的生物标志物。在这项三向交叉研究中，18名健康的老年人（年龄：65-80岁）受试者接受了5毫克唑吡坦，10毫克suvorexant,或者早上服用安慰剂.在给药前和大约每小时进行评估，直到给药后9小时。IWW评估包括8米步行测试，以目标为导向的踏步，避障,和串联行走。其他药效学测量是以舒适和快速的节奏进行定时向上（TUG）测试，自适应跟踪,和身体摇摆。在IWW步行适应性结果测量中，与安慰剂相比，唑吡坦在给药后3小时观察到性能下降。TUG,自适应跟踪,和身体摇摆。对于IWW任务，观察到步行速度（除其他外）下降。与安慰剂相比，在任何时间点IWW参数均不受suvorexant影响。然而,增长9.8%（95CI：1.8%，与安慰剂相比，suvorexant在服药后3小时内观察到了18.5％）的身体摇摆。IWW成功地量化了两种催眠药物的药物作用，并区分了唑吡坦和苏沃雷生对行走的影响。作为生物标志物,在早期临床药物开发中,IWW在评估动态平衡和潜在跌倒风险方面表现出敏感性.
