General Information

Hetlioz (tasimelteon) is an agonist at melatonin MT1 and MT2 receptors. These receptors are thought to be involved in the control of circadian rhythms. The precise mechanism by which tasimelteon exerts its therapeutic effect in patients with Non­ 24 is not known.

Hetlioz is specifically indicated for the treatment of non-24-hour sleep-wake disorder in the totally blind.

Hetlioz is supplied as a capsule for oral administration. The recommended dosage of Hetlioz is 20 mg per day taken before bedtime, at the same time every night. Because of individual differences in circadian rhythms, drug effect may not occur for weeks or months.

Clinical Results

FDA Approval
The FDA approval of Hetlioz was based on two randomized, double blind, placebo controlled parallel groups studies (Study 1 and 2) in totally blind subjects with non-24-hour sleep-wake disorder (non-24). In study 1, 84 subjects (median age 54 years) were randomized to receive Hetlioz 20 mg or placebo, one hour prior to bedtime, at the same time every night for up to 6 months. Study 2 was a randomized withdrawal trial in 20 subjects (median age 55 years) that was designed to evaluate the maintenance of efficacy of Hetlioz after 12-weeks. Subjects were treated for approximately 12 weeks with Hetlioz 20 mg one hour prior to bedtime, at the same time every night. Subjects in whom the calculated time of peak melatonin level (melatonin acrophase) occurred at approximately the same time of day (in contrast to the expected daily delay) during the run-in phase were randomized to receive placebo or continue treatment with Hetlioz 20 mg for 8 weeks. Both studies evaluated the duration and timing of nighttime sleep and daytime naps via patient-recorded diaries. During Study 1, diaries were recorded for an average of 88 days during screening, and 133 days during randomization. During Study 2, diaries were recorded diaries were recorded for an average of 57 days during the run-in phase , and 59 days during the randomized withdrawl phase. Efficacy endpoints for nighttime total sleep time and daytime nap duration were based on the 25% of nights with the least nighttime sleep, and the 25% of days with the most daytime nap time. In both studies, treatment with Hetlioz resulted in a significant improvement, compared with placebo, for both of these endpoints. Study 1: Change from baseline for nighttime sleep time on 25% most symptomatic nights: 50 minutes increase for Hetlioz vs. 22 minutes for placebo; Change from baseline for daytime nap time on 25% most symptomatic days: -49 minute reduction for Hetlioz and -22 minutes for placebo. Study 2: Change from baseline for nighttime sleep time on 25% most symptomatic nights: -7 minutes for Hetlioz vs. -74 minutes for placebo; Change from baseline for daytime nap time on 25% most symptomatic days: -9 minute reduction for Hetlioz versus 50 minute increase for placebo.

Side Effects

Adverse events associated with the use of Hetlioz may include, but are not limited to, the following:

• headache
• increased alanine aminotransferase
• nightmares or unusual dreams
• upper respiratory or urinary tract infection

Mechanism of Action

Hetlioz (tasimelteon) is an agonist at melatonin MT1 and MT2 receptors. These receptors are thought to be involved in the control of circadian rhythms. The precise mechanism by which tasimelteon exerts its therapeutic effect in patients with Non­ 24 is not known.

Additional Information

For additional information regarding Hetlioz or non­24-hour sleep-wake disorder, please visit the Hetlioz web page.