One such study enrolled 75 patients age 18–45 years with subjective sleep latency less than 30 minutes and subjective TST between 6.5 and 9 hours in a randomized, double-blind, placebo controlled trial.
While the majority of research with ramelteon has surrounded use in primary insomnia, studies have also attempted to evaluate its use in circadian rhythm sleep disorders. The results from these two trials led to the FDA approval of ramelteon in adults for the treatment of insomnia characterized by difficulty with sleep onset, but not sleep maintenance as its use did not lead to sustained increases in TST during the duration of these studies. However, a significant increase in TST was only observed during evaluations at week 1 in participants who received ramelteon compared to placebo (281.1 minutes vs. Participants who received ramelteon had statistically significant improvements in LPS compared with placebo throughout the 6 month treatment period (week 1, months 1, 3, 5 and 6 all p<0.05).
Again, the majority of participants were Caucasian women with an average age of 46.2 years. Three hundred thirty five participants completed the treatment period. Exclusion criteria were also similar, except patients with sleep disorders other than insomnia were also excluded. 13 Included participants were adults with chronic insomnia with similar symptoms as the previous trial but with a subjective sleep latency of at least 45 minutes and a regular bedtime between 10 pm and 1 am. The second trial was a 6-month, multicenter, randomized, double-blind, placebo-controlled study that evaluated ramelteon 8 mg in a similar patient population and with similar medication administration. Additional secondary outcomes such as TST and sleep efficiency were also statistically significantly improved with ramelteon compared to placebo at the week 1 assessment (both p<0.001). The authors reported a 15–17 minute greater reduction in LPS in participants who received ramelteon than those who received placebo. During assessments at week 1, 3, and 5, participants who received 8 or 16 mg of ramelteon had significant improvements in LPS compared to those who received placebo (at week 1: 32.2, 28.9 and 47.9 minutes respectively p<0.001). Three hundred sixty seven participants completed the study, the majority of which were Caucasian females. During the treatment period, participants received 8 or 16 mg of ramelteon or placebo 30 minutes prior to bedtime and start of PSG. Notable exclusions included patients who participate in shift work, had recently taken a flight across greater than 3 time zones, or had any mental illness or other significant disease states. Participants were 18–64 years of age with a diagnosis of primary insomnia, reporting subjective sleep latency of at least 30 minutes, subjective total sleep time (TST) less than 6.5 hours per night and symptoms during the day related to their disrupted sleep. 12 The first was a 5-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial.
Initial efficacy data supporting the use of ramelteon in adults for insomnia was based on one short-term and one longer-term clinical trial which both utilized polysomnography (PSG) to assess latency to persistent sleep (LPS). 3 It is slated to be reviewed by the FDA in the first quarter of 2014. In November 2013, the Federal Drug Administration (FDA) advisory panel voted in favor of tasimelteon. 1 Recently, Vanda Pharmaceuticals submitted a New Drug Application for tasimelteon (Hetlioz ®), for the treatment of non-24 SWD in the totally blind. 1 Persons with this disorder experience a consistent daily shift in the time of sleep onset and time awake, with sleep onset occurring at a later and later time. 1 Non-24 SWD is a circadian rhythm sleep-wake disorder characterized by sleeping and being awake during times that are not synchronized with the typical 24-hour environment. 1 These disorders are further classified as delayed sleep phase type, advanced sleep phase type, irregular sleep-wake type, shift-work type, and non-24-hour sleep-wake disorder (non-24 SWD). Circadian rhythm disorders are related to sleep disturbances secondary to a change in the circadian system or discordance between the circadian rhythm and a person's sleep-wake schedule. Sleep disorders extend beyond insomnia, and research is being done for pharmaceutical targets of other disorders.
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