Zolpidem Tartrate Sublingual Tablets to Treat Insomnia

Boston—According to a post hoc analysis of a double-blind, placebo-controlled cross-over study, patients who took 1.75 mg and 3.5 mg of zolpidem tartrate sublingual tablets had a significantly shorter time to sleep compared with those who took placebo. In addition, a similar percentage of males and females who took the recommended dose of zolpidem tartrate sublingual tablets fell asleep within 20 minutes of middle-of-the-night awakening.

Results were presented at the SLEEP meeting during a poster session. The poster was titled Gender Effects of 1.75-mg and 3.5-mg Zolpidem Tartrate Sublingual Tablets Formulated with a Carbonate-Bicarbonate Buffer on Sleep Onset Following Middle-of-the-Night Awakening and on Next Day Residual Effects.

The FDA approved zolpidem tartrate sublingual tablets in November 2011 as the first drug to treat insomnia for adults who have middle-of-the-night waking followed by difficulty sleeping. The drug is intended for use when there are ≥4 hours of bedtime remaining before a person is expected to awake. The maximum recommended dose is 1.75 mg for females and the elderly (≥65 years of age), and 3.5 mg for males.

The study enrolled 82 adults who were between 18 and 64 years of age with a body mass index between 18 and 34. They were required to have a diagnosis of insomnia as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. Other inclusion criteria included a history of middle-of-the-night awakenings for ≥4 weeks, which were defined as ≥3 nights per week with an awakening episode and a sleep onset latency of ≥30 minutes per awakening.

Patients were randomized to receive 1.75 mg or 3.5 mg of zolpidem tartrate sublingual tablets or placebo, although only the 1.75-mg dosage is approved for females and the elderly (≥65 years of age). There were 3 treatment periods (each separated by 5 to 12 days) during which treatments were administered on 2 consecutive nights.

After 4 hours of sleep at night, patients were given the study drug and remained awake for 30 minutes before sleeping for an additional 4 hours. Within 30 minutes of waking, they completed a questionnaire. The researchers recorded the polysomnographic mean sleep latency for 8 hours on each of the 6 nights of treatment, 4 hours before the middle-of-the-night awakening, and 4 hours after awakening.

The authors concluded there was a statistically significant improvement in total sleep time after a scheduled awakening in the zolpidem tartrate sublingual tablets group compared with the placebo group. The results were consistent when reported by patients or measured by polysomnographic mean sleep latency.

Within 20 minutes after awakening, 60% of females in the 1.75-mg group and 80% of females in the 3.5-mg group were asleep compared with 46% of males in the 1.75-mg group and 63% of males in the 3.5-mg group.

Of the 82 patients, 12 reported having an adverse event (AE). There were 8 AEs in females and 7 in males. All adverse events were mild or moderate in severity, according to the authors.

This study was supported by Purdue Pharma L.P. and Transcept Pharmaceuticals, Inc.