Citation

Koopmans I, Geerse D, de Ridder L, Roerdink M, Juachon MJ, Muehlan C, Dingemanse J, van Gerven J, Groeneveld GJ, Zuiker R. Clin. Transl. Sci. 2024; 17(7): e13875.

Copyright

(Copyright © 2024, John Wiley and Sons)

DOI

10.1111/cts.13875

PMID

38978326

PMCID

PMC11231031

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.

Language: en

Keywords

Humans; Aged; Female; Male; Aged, 80 and over; Biomarkers; Double-Blind Method; *Accidental Falls/prevention & control; *Cross-Over Studies; *Walking/physiology; Risk Assessment/methods; *Azepines/administration & dosage/adverse effects; *Postural Balance/drug effects/physiology; *Triazoles/administration & dosage/adverse effects; *Zolpidem/administration & dosage/adverse effects; Pyridines/administration & dosage/adverse effects