¹HPRU Medical Research Centre, University of Surrey, Sanofi-Synthelabo Research, Guildford, United Kingdom

Abstract

Aims/Background: To determine the modified-release (MR) formulation of zolpidem that provides optimal sleep maintenance without next-day residual effects.

Methods: A randomized, double blind, placebo- and reference-controlled, 10-way crossover study conducted in 36 healthy volunteers (18 to 40 year old, 20 male) comparing single nocturnal doses of 8 zolpidem MR formulations (A-H, up to 15 mg) or standard zolpidem 10 mg to placebo. Polysomography (PSG) criteria and sleep architecture were recorded for 8h postdose; a traffic noise model induced sleep maintenance difficulties. Psychometric testing was conducted 8 and 9h postdose. Morning plasma zolpidem levels were checked for residual effects. Study periods were separated by 7 days wash-out.

Results: Hourly PSG analysis showed Formulation E (12.5 mg) significantly reduced the mean number of awakenings up to 5 hr postdose. Pairwise comparisons vs. placebo showed a decreasing trend in the duration of awakenings for 4 formulations, including E, up to 5h postdose. Psychomotor test performance was not significantly different from placebo or standard zolpidem 8 and 9h postdose.

Conclusion: This study demonstrates the zolpidem MR 12.5 mg successfully improves sleep maintenance during the middle of the night with respect to placebo and standard zolpidem, without compromise to next-day psychomotor performance or sleep architecture. All zolpidem MR formulations and standard zolpidem were well tolerated with no safety issues observed.