A 12-week, randomized, double-blind, placebo-controlled study evaluating the effect of eszopiclone 2 mg on sleep/wake function in older adults with primary and comorbid insomnia

Abstract

Background: Longer-term pharmacologic studies for insomnia in older individuals are sparse.

Objective: To evaluate the efficacy and safety of 12 weeks of nightly eszopiclone in elderly outpatients with insomnia.

Methods: Participants (65-85 years) met DSM-IV-TR criteria for insomnia with total sleep times (TST) < or = 6 h, and wake time after sleep onset (WASO) > or = 45 min. Participants were randomized to 12 weeks of eszopiclone 2 mg (n = 194) or placebo (n = 194), followed by a 2-week single-blind placebo run-out. Subject-reported measures of sleep (sTST, sleep latency [sSL], sWASO) and daytime function (alertness, concentration, wellbeing, ability to function) were assessed. AEs were monitored.

Results: Subjects treated with 2 mg eszopiclone slept longer at night on average and at every individual time point compared to baseline than placebo subjects, as measured by TST over the 12-week double-blind period (P < 0.0001). Mean sTST over the double-blind period for eszopiclone-treated subjects was 360.08 min compared to 297.86 min at baseline, a mean change of 63.24 min. Over the double-blind period, eszopiclone-treated subjects also experienced a significantly greater improvement in sSL compared to placebo, with a mean decrease of 24.62 min versus a mean decrease of 19.92 min, respectively (P = 0.0014). Eszopiclone subjects also experienced a significantly greater decrease in WASO (mean decrease of 36.4 min) compared to placebo subjects (decrease of 14.8 min) (P < 0.0001). Post-discontinuation, sleep parameters were statistically improved versus baseline for eszopiclone (P-values < or = 0.01), indicating no rebound. The most common AEs (> or = 5%) were headache (eszopiclone 13.9%, placebo 12.4%), unpleasant taste (12.4%, 1.5%), and nasopharyngitis (5.7%, 6.2%).

Conclusion: In this Phase IV trial of older adults with insomnia, eszopiclone significantly improved patient-reported sleep and daytime function relative to placebo. Improvements occurred within the first week and were maintained for 3 months, with no evidence of rebound insomnia following discontinuation. The 12 weeks of treatment were well tolerated.

Clinical trial information: A Long-Term Safety and Efficacy Study of Eszopiclone in Elderly Subjects With Primary Chronic Insomnia; Registration #NCT00386334; URL - http://www.clinicaltrials.gov/ct2/show/NCT00386334?term=eszopiclone&rank=24

Figure 1

Study flow and patient disposition *Thirty-six subjects dropped out of the study during the single-blind placebo run-in phase. The other 9 subjects were screen failures. †3 subjects did not meet the criteria of TST ≤ 6 hours on 4 or more nights; 1 subject was non-compliant with visit schedules due to vacation. ‡1 subject did not meet the criteria of TST ≤ 6 hours on 4 or more nights; 1 subject took excluded psychiatric medications for an undisclosed psychiatric condition; 1 subject started working nights; 1 subject was enrolled in 2 investigational studies simultaneously; 1 subject had a positive urine drug screen for barbiturates.

Figure 2

Subject-reported sleep efficacy during 12 weeks of treatment and after discontinuation Mean (SEM) sSL, sWASO, and sTST at each assessment time point during 12 weeks of double-blind treatment, and on each day after treatment discontinuation. Values represented at each week of the double-blind treatment period are for the ITT population (N = 194 in the eszopiclone group; N = 194 in the placebo group). Values represented on each day after treatment discontinuation are for those participants who completed double-blind treatment and received at least one dose of single-blind placebo (N = 145 in the eszopiclone group; N = 146 in the placebo group). Time 0 represents the baseline value at the start of the double-blind treatment period.

Figure 3

Number of reported naps/week and total daily nap time/week The mean (SEM) number of naps per week (top) and mean (SEM) total daily naptime per week (bottom) at each assessment time point. P-values are based on ANCOVA vs. placebo. BL, baseline.

Figure 4

Insomnia Severity Index total scores with clinical categories Mean (SEM) ISI total scores at each assessment time point. Clinical categories were based on the ISI total scores: 0–7 = no clinically meaningful insomnia; 8–14 = sub-threshold insomnia; 15–21 = moderate insomnia; 22–28 = severe insomnia. BL, baseline.

Figure 5

Distribution of ISI total scores Percentage of participants with ISI total scores categorized as no insomnia, sub-threshold insomnia, moderate insomnia, and severe insomnia at baseline, at the end of 12 weeks of treatment (Week 12), the end of the single-blind placebo period (Week 14), and the end of the no-drug period (Week 16). PBO, placebo; ESZ, eszopiclone 2 mg; End DB, end of double-blind period; End SB, end of single-blind placebo period; End ND, end of no-drug period. The shift in distribution of scores from Week 12 to Week 14 and Week 14 to Week 16 were analyzed using the Stuart-Maxwell test.