Sepracor Announces Publication of Additional Data from Lunesta Insomnia-Depression Study in the Journal of Clinical Sleep Medicine
The double-blind, placebo-controlled study evaluated the efficacy and safety of LUNESTA in patients who met DSM-IV(R)(1) criteria for both insomnia and MDD (either newly diagnosed or patients who had a new recurrence of MDD). Patients were randomized to receive open-label fluoxetine each morning and either double-blind LUNESTA 3 mg (n=270) or matching placebo (n=275) nightly for the first eight weeks, followed by a two-week period during which all patients received single-blind placebo treatment and continued receiving fluoxetine.
Journal of Clinical Sleep Medicine Published Results
The study endpoints contained in the Journal of Clinical Sleep Medicine manuscript were the evaluation of withdrawal effects during the two-week discontinuation period, which is also referred to as the run-out period, by examining: 1) the prevalence of new or worsening CNS (central nervous system)-related adverse events, 2) rebound insomnia, and 3) worsening of MDD symptoms. The rebound insomnia variables were assessed using an interactive voice response system (IVRS) during the run-out period and they included sleep onset, wake time after sleep onset (WASO), total sleep time (TST), and measures of daytime functioning.
Sleep and daytime function were also assessed subjectively during the run-out period using the insomnia severity index (ISI) scale, which consists of self-ratings of difficulties with sleep onset, sleep maintenance, and early morning awakenings, as well as daytime function, degree of impairment, and concern and satisfaction with current sleep pattern. Depressive symptoms were assessed during the run-out period using the HAM-D17 scale (Hamilton Depression Rating Scale, the standard scale used by clinicians in research studies to assess depression; the HAM-D17 is a list of symptoms commonly associated with depression; a lower score indicates fewer symptoms of depression). The HAM-D17 was also used to evaluate antidepressant response and remission rates. In addition, at Weeks 8 and 10, antidepressant efficacy was evaluated using Clinical Global Impression Improvement (CGI-I) and Severity (CGI-S) scales (used by clinicians to assess improvement in a patient's MDD symptoms and the severity of their depression at various time points, respectively).
In this study, patients discontinued from LUNESTA maintained improvements from baseline in sleep onset, WASO, and TST during the two-week discontinuation period (p less than 0.05). LUNESTA discontinuation did not result in significant CNS withdrawal adverse events, rebound insomnia or rebound depression, and improvements in sleep and depressive symptoms were maintained. The improvements in the HAM-D17 scale scores with and without the three sleep items observed with co-therapy versus monotherapy at Week 8 (p less than 0.02) were maintained at Week 10 (p less than 0.002) in the group initially randomized to co-therapy.
Previously Published Results From the Insomnia-Depression Study
The results of the double-blind, placebo-controlled insomnia-depression study of LUNESTA were published in the June 2006 edition of the journal, Biological Psychiatry. The primary endpoint for this study was WASO, and secondary endpoints included additional sleep parameters and overall HAM-D17 scores. Other key secondary endpoints included 30% antidepressant response (30% reduction from baseline) and time to 30% antidepressant response based on Bech and Maier subscales of patient-reported HAM-D17, which do not contain sleep-related items.
Throughout the double-blind treatment period, which was the first eight weeks of the study, patients treated with LUNESTA plus fluoxetine showed improvements in time to sleep onset (p less than or equal to 0.0001), WASO (p less than or equal to 0.002) and TST (p less than or equal to 0.0004), compared to those patients taking placebo plus fluoxetine. In this study, there was no evidence of tolerance to sleep efficacy (no waning of effect) across the eight weeks of treatment, and there was no rebound insomnia upon discontinuation of LUNESTA. Patients receiving LUNESTA plus fluoxetine also reported improvements in sleep quality (p less than or equal to 0.0002) and depth of sleep (p less than or equal to 0.0007) relative to patients receiving placebo plus fluoxetine. Averaged over the double-blind period, patients receiving LUNESTA plus fluoxetine also reported improved daytime alertness (p=0.03), ability to think clearly and concentrate (p=0.02) and ability to function (p=0.007) relative to patients receiving placebo plus fluoxetine.
Patients co-administered LUNESTA with fluoxetine demonstrated reductions (p=0.01) in overall HAM-D17 scores at Week 4, and there was a progressive improvement at Week 8 (p=0.002), versus patients in the placebo-fluoxetine group. After removing insomnia-specific questions from HAM-D17, improvements in scores remained significant at Week 8 (p=0.04). At Week 8, 59% of LUNESTA-fluoxetine-treated patients were responders (patients experiencing a 50 percent or greater decrease in their HAM-D17 scores; p=0.009) versus 48% of patients in the placebo-fluoxetine group, and 42% of the LUNESTA-fluoxetine-treated patients were remitters (patients who have HAM-D17 scores of 7 or lower and are therefore considered to no longer be depressed; p=0.03) versus 33% of patients in the placebo-fluoxetine group. Patients in the LUNESTA-fluoxetine group also demonstrated shorter times to antidepressant response based on CGI-I (p=0.0002) and CGI-S (p=0.01) as compared to the placebo-fluoxetine group. Fewer patients in the LUNESTA-fluoxetine group (44.7%; p=0.04) required titration to a higher dose of fluoxetine as compared to those in the placebo-fluoxetine control group (53.7%). The LUNESTA-fluoxetine treatment group did not show a worsening of depression as compared to the placebo-fluoxetine group, and the LUNESTA-fluoxetine combination appeared to result in greater improvement in HAM-D17 scores than was observed in the placebo-fluoxetine group. There were no significant differences between the treatment groups at any assessment point on patient-reported Bech and Maier subscales of the HAM-D17, and there were no significant differences in the 30% antidepressant response or time to onset of a 30% response with patient-reported Bech and Maier subscales. However, clinician-rated versions of the Bech and Maier subscales were improved in the LUNESTA-fluoxetine treatment group at both assessment points (Week 4, p less than 0.05; Week 8, p less than 0.05) during the double-blind period.
Study completion rates were similar in both the placebo- and LUNESTA-treated groups, and LUNESTA and fluoxetine co-administration was well tolerated.
An estimated one third of all adults in the U.S. suffer from either chronic or occasional insomnia.(2) Symptoms of insomnia include difficulty falling asleep, awakening frequently during the night, waking up too early, an inability to fall back to sleep, or awakening feeling unrefreshed.
Important Safety Information
LUNESTA is indicated for the treatment of insomnia. LUNESTA is not indicated for the treatment of depression. LUNESTA works quickly and should only be taken immediately before bedtime. Patients should have at least eight hours to devote to sleep before becoming active. Patients should not engage in any activity after taking LUNESTA that requires complete alertness, such as driving a car or operating machinery. Patients should use extreme care when engaging in these activities the morning after taking LUNESTA. Patients should not use alcohol while taking any sleep medicine. Most sleep medicines carry some risk of dependency. Patients should not use sleep medicines for extended periods without first talking to their doctor. Patients should see their doctor if they experience unusual changes in thinking or behavior, or if sleep problems do not improve in 7 to 10 days as this may be due to another medical condition. Side effects may include unpleasant taste, headache, drowsiness and dizziness.
Sepracor Inc. is a research-based pharmaceutical company dedicated to treating and preventing human disease by discovering, developing and commercializing innovative pharmaceutical products that are directed toward serving unmet medical needs. Sepracor's drug development program has yielded a portfolio of pharmaceutical products and candidates with a focus on respiratory and central nervous system disorders. Sepracor's corporate headquarters are located in Marlborough, Massachusetts.
This news release contains forward-looking statements that involve risks and uncertainties, including statements with respect to the safety, efficacy and potential benefits of LUNESTA brand eszopiclone. Among the factors that could cause actual results to differ materially from those indicated by such forward-looking statements are: Sepracor's ability to fund, and the results of, further clinical trials; the timing and success of submission, acceptance, and approval of additional regulatory filings; the scope of Sepracor's patents and the patents of others; the commercial success of LUNESTA; the ability of the company to attract and retain qualified personnel; and certain other factors that are detailed in the company's quarterly report on Form 10-Q for the quarter ended September 30, 2006 filed with the Securities and Exchange Commission.
In addition, the statements in this press release represent Sepracor's expectations and beliefs as of the date of this press release. Sepracor anticipates that subsequent events and developments may cause these expectations and beliefs to change. However, while Sepracor may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Sepracor's expectations or beliefs as of any date subsequent to the date of this press release.
1 Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition
2 Ancoli-Israel et al. SLEEP. 1999;22 (suppl 2):S347-S353
LUNESTA is a registered trademark of Sepracor Inc. PROZAC is a registered trademark of Eli Lilly and Company. DSM-IV is a registered trademark of the American Psychiatric Association. For a copy of this release or any recent release, visit Sepracor's web site at www.sepracor.com.
David P. Southwell
Executive Vice President
Chief Financial Officer
Jonae R. Barnes
Posted: February 2007