A randomized double-blind placebo-controlled 10-way crossover study to show that a new zolpidem modified-release formulation improves sleep maintenance compared to standard zolpidem

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. Clinical Pharmacology & Therapeutics (2005) 77, P26–P26; doi: 10.1016/j.clpt.2004.11.100