A polysomnographic placebo-controlled evaluation of the efficacy and safety of eszopiclone relative to placebo and zolpidem in the treatment of primary insomnia

Abstract

Study objectives: To evaluate the polysomnographic efficacy and the safety of a range of doses of eszopiclone relative to placebo in patients with primary insomnia. Zolpidem 10 mg was included as an active control.

Methods: This multicenter, randomized, crossover study enrolled patients aged 21-64 years meeting the DSM-IV criteria for primary insomnia (n = 65). Patients received 2 nights treatment each with placebo, eszopiclone 1 mg, 2 mg, 2.5 mg, or 3 mg, and zolpidem 10 mg after randomization to one of 6 treatment sequences. Visits were separated by a 3-7 day washout. Objective efficacy was assessed by polysomnography (PSG). The primary endpoint was latency to persistent sleep (LPS); key secondary endpoints were sleep efficiency (SE) and wake time after sleep onset (WASO); other endpoints included wake time during sleep (WTDS) and number of awakenings (NAW), as well as patient-reported variables.

Results: LPS and SE were significantly different than placebo for all active treatments (p < 0.05 for all). Significant differences from placebo were noted in the 3 objective sleep maintenance measures (WASO, WTDS, and NAW) for eszopiclone 3 mg (p < 0.05), which was not the case for zolpidem 10 mg or the other eszopiclone doses. The incidence of central nervous system adverse events was 23.4% for zolpidem 10 mg, 6.2% to 12.5% for the eszopiclone doses, and 7.9% for placebo.

Conclusions: Relative to placebo, all active treatments were effective in reducing LPS and increasing SE. Eszopiclone 3 mg was significantly different from placebo on the 3 PSG measures of sleep maintenance (WASO, WTDS, and NAW). Significant differences between zolpidem 10 mg and eszopiclone (2 mg or 3 mg) were not observed for PSG-measured outcomes, although the study was not powered to detect differences between the active drug conditions.

Conflict of interest statement

Disclosure Statement

Support for this study provided by Sepracor Inc. Dr. Erman has received research support from Sanofi, Takeda, Pfizer, Pharmacia, Merck, Schwarz, Organon, GlaxoSmithKline, Eli Lilly, Wyeth, and Neurocrine Biosciences; has consulted for Sanofi, Mallinckrodt, Cephalon, Takeda, and Neurocrine Biosciences; is on the advisory board of Sanofi, Cephalon, Takeda, and Neurocrine Biosciences; is on the speaker's bureau of Sanofi and Takeda; and has financial interests in Cephalon, Forest, Neurocrine Biosciences, Pfizer, Sepracor, Sanofi, and Somaxon. Dr. Zammit has received research support from Ancile Pharmaceuticals, Arena, Aventis, Cephalon, Elan, Epix, Evotec, Forest, GlaxoSmithKline, H. Lundbeck A/S, King, Merck, Neurim, Neurocrine Biosciences, Neurogen, Organon, Orphan Medical, Pfizer, Respironics, Sanofi-Aventis, Schering-Plough, Sepracor, Somaxon, Takeda, Transcept, UCB Pharma, Predix, Vanda, and Wyeth-Ayerst; has consulted for Aventis, Boehringer Ingelheim, Cephalon, Elan, GlaxoSmithKline, Jazz, King, Merck, Neurocrine Biosciences, Organon, Pfizer, Renovis, Sanofi-Aventis, Select Comfort, Sepracor, Shire, and Takada; has received honoraria from Neurocrine Biosciences, Kink, McNeil, Sanofi-Aventis, Sanofi-Synthelabo, Sepracor, Shire, and Takeda; and has ownership/Directorship in Clinilabs, Inc., Clinilabs IPA, Inc., and Clinilabs Physician Services, PC. Dr. Walsh has consulted for Pfizer, Sanofi-Aventis, Cephalon, Organon, Neurocrine Biosciences, Takeda, Actelion, Sepracor, Elan, Guilford, Respironics, Merck KgaA-Darmstadt, King, TransOral, Neurogen, GlaxoSmithKline, SleepTech, Somaxon, Eli Lilly, Evotec, Neurosciences, and Merck. Drs. Rubens, Wessel, Amato, Caron, and Ms. Schaefer are employees of Sepracor.

Figures

Figure 1

Median objective sleep efficiency (SE), as determined by PSG. *p ∧p < 0.05 vs. eszopiclone 1.0 mg.

Figure 2

Median wake time after sleep onset (WASO), as determined by PSG. *p ∧p < 0.02 vs. eszopiclone 1.0 mg.

Figure 3

Median wake time during sleep (WTDS), as determined by PSG. *p