A randomized double-blind placebo-controlled3-way crossover study investigating psychomotor and cognitive residual effects of a new zolpidem modified-release formulation in healthy volunteers

Abstract

Aims/Background To assess the residual psychomotor and cognitive effects and safety of a new zolpidem modified-release (MR) formulation 8h after a single dose. Methods A randomized, double-blind, placebo- and reference-controlled, 3-period crossover study in 18 healthy volunteers (22 to 38 years old, 10 male) comparing zolpidem MR 12.5 mg or flurazepam 30 mg to placebo. Cognitive and psychomotor tests were performed 8h postdose: Critical Flicker Fusion (CFF), Choice Reaction Time (CRT), Compensatory Tracking Time (CTT), Immediate and Delayed Word Recall (WRi, WRd), and Digit Symbol Substitution Test (DSST). Subjective sleep quality was evaluated using the Leeds Sleep Evaluation Questionnaire. Clinical laboratory parameters, vital signs, and adverse event recording evaluated safety. Results Pairwise comparisons between zolpidem MR and placebo demonstrated no significant difference in performance in CFF, CRT, WRi, WRd and DSST, 8h postdose. A significant increase in CTT time reaction was half that observed with flurazepam. Flurazepam significantly impaired performance in all tests except DSST compared to placebo. Conclusion This study demonstrates that unlike flurazepam (positive control), zolpidem MR 12.5 mg has no residual effects on CNS integrative capacity, sensorimotor or psychomotor performance, immediate and delayed memory recall except for CTT time reaction compared to placebo. Zolpidem MR is well tolerated and exhibits a comparable safety profile to placebo. Clinical Pharmacology & Therapeutics (2005) 77, P27–P27; doi: 10.1016/j.clpt.2004.11.106