SAN FRANCISCO – Tasimelteon, an experimental melatonin receptor agonist, reset the internal clock of blind patients to a 24-hour cycle in a randomized trial by Vanda Pharmaceuticals, its maker.
The 84 totally blind subjects had non-24-hour sleep-wake disorder, meaning that their circadian rhythms were out of synch with the external world, causing sleep and daytime performance problems. That’s not uncommon in blindness; without the regulating effects of perceived light, internal clocks revert to their intrinsic rhythm of about 24.5 hours.
Forty-two patients were randomized to 20 mg of tasimelteon 1 hour before bedtime for 6 months, and 42 others to placebo. Entrainment to a 24-hour cycle was gauged by the timing of peak urinary excretions of cortisol and 6-sulfatoxymelatonin, a melatonin metabolite.
Dr. Steven Lockley
Eight patients on tasimelteon synched up to the 24-hour clock, and 10 both entrained and had improvements in various sleep and function measures. One placebo patient entrained during the trial, and none had improvements in sleep or function.
In a follow-up study, 10 entrained tasimelteon patients were randomized to continue the drug, and 10 others to switch to placebo. One tasimelteon patient, but eight placebo patients, reverted to a non-24-hour cycle. "Maintenance is required to maintain entrainment and clinical benefit," said lead investigator Steven Lockley, Ph.D., a neuroscientist in the division of sleep medicine at Brigham and Women’s Hospital in Boston.
"The medication is able to replace the time cue usually provided by light and synchronize the circadian clock in totally blind people. None of the traditional medications used to treat sleep disorders or sleepiness have this ability," he said at the Endocrine Society’s annual meeting.
Vanda filed with the Food and Drug Administration in May for an indication to treat non-24-hour sleep-wake disorder in totally blind patients. The drug might also prove useful for other circadian problems, Dr. Lockley said.
Side effects included nausea, headache, and sleepiness, but were uncommon and not significantly more frequent than with placebo. Subjects were aged 21-84 years, and 34 were women.
Dr. Lockley is an investigator for Vanda Pharmaceuticals, which funded the work. Another investigator is a consultant to the company, and the remaining six are employees.