Beating the Biological Clock – Clinical Trials of Tasimelteon

The Lancet recently published clinical trial data from a Harvard study which compares the experimental new drug tasimelteon to placebo in treating jet lag. The medication works by binding to the same receptor as melatonin, and activating it as a direct agonist.

Melatonin is a neurotransmitter produced by the brain that is believed to play a pivotal role in the regulation of our “biological clock” or circadian rhythm. Melatonin levels fluctuate in the bloodstream throughout the day, and surge during the nighttime hours when it is dark outside and our bodies are inclined to sleep. The trouble with melatonin is that it falls under the FDA category of supplements and nutraceuticals, and is therefore largely unregulated in terms of potency, manufacturing process, and quality of ingredients. Studies are hard to conduct and successfully repeat for this reason as well.

Tasimelteon was studied in a multicenter, randomized, placebo-controlled clinical trial for its phase III testing. The study recruited 411 healthy volunteers aged 21-50, who were randomized to receive either a placebo, or tasimelteon at 20 mg, 50 mg, or 100 mg. The volunteers were observed in a sleep clinic for 7 nights. The first 3 nights they went to sleep at their normal bedtime and did not receive any medication. Measurements were taken regarding the time to fall asleep, quality of sleep, and duration of sleep before waking. For the next 3 nights, the volunteers attempted to fall asleep 5 hours prior to their established bedtime to simulate jet lag, and were given their respective medication/placebo dose 30 minutes prior to their attempt. The same measurements were taken. On the 7th day, volunteers returned to their established bedtime but also received their medication/placebo 30 minutes prior. Measurements again were taken.

The results of the trial were that subjects who received tasimelteon fell asleep quicker, had a deeper and more efficient quality of sleep, and slept longer than subjects who received the placebo. The benefits were also dose-dependent, meaning the benefits improved as the dosage went from 20 mg to 50 mg to 100 mg. Side effect profiles were similar to placebo across all groups. Given this strong phase III data, the medication may be approved by the FDA and available to the public within the next 2-3 years.

Two to three years may be too long for airline pilots, shift workers, or any other frequent travelers who deal with jet lag on a regular basis. Current options for the management of jet lag are lackluster. Benzodiazepines are the main option, can be habit-forming, and have several untoward side effects. Hypnotics are also habit-forming, and must be timed appropriately because one cannot operate machinery or drive for several hours after being taken. Melatonin has no conclusive clinical data proving that it works, and as mentioned above, obtaining a quality product can be difficult. A medication like tasimelteon would be a welcome addition as it appears to have very few side effects, is not habit-forming, and works by altering circadian rhythms to allow a patient to fall asleep and stay asleep naturally.

Reference

S RAJARATNAM, M POLYMEROPOULOS, D FISHER, T ROTH, C SCOTT, G BIRZNIEKS, E KLERMAN (2008). Melatonin agonist tasimelteon (VEC-162) for transient insomnia after sleep-time shift: two randomised controlled multicentre trials The Lancet DOI: 10.1016/S0140-6736(08)61812-7