SLEEP: Rozerem (ramelteon) Found Safe and Effective In Transient Insomnia

June 21, 2006

SALT LAKE CITY - Rozerem (ramelteon), a melatonin agonist, was found both safe and effective in a laboratory model of transient insomnia.

SALT LAKE CITY, June 21 - Rozerem (ramelteon), a melatonin agonist approved a year ago as an unscheduled agent for insomnia, was found both safe and effective in a laboratory model of transient insomnia, a New York researcher said here.

The medication reduced the time it took for participants to fall asleep, increased the quality of sleep, and had no residual psychomotor or memory effects the following day, said Gary Zammit, Ph.D., of St. Luke's-Roosevelt Hospital in New York.

The finding is valuable because it gives physicians and patients a medication that can be taken on an unscheduled basis to cope with occasional insomnia, Dr. Zammit reported in a poster at Sleep 2006, the joint meeting of the Sleep Research Society and the American Academy of Sleep Medicine.

Dr. Zammit and colleagues enrolled 289 healthy adults in a randomized, placebo-controlled parallel-group study of two different doses of Rozerem, 8 mg and 16 mg. The study was supported by Takeda Pharmaceuticals of Lincolnshire, Ill., the developer of Rozerem, a melatonin agonist that binds to the MT1 and MT2 receptors in the brain.

The participants were brought into a sleep lab for a single night, Dr. Zammit said in an interview. "When we bring people into the sleep laboratory for one night, they have what's called a "first-night effect-they take longer to fall asleep and their sleep is disrupted," he said.

The situation is an "ideal model" for transient insomnia-the familiar situation of occasionally being unable to get to sleep, Dr. Zammit said.

The study found:

  • Those taking 8 mg of Rozerem fell asleep on average in 12.2 minutes, compared with 19.7 for placebo patients, a difference that was statistically significant at P=0.004.
  • Those taking 16 mg also fell asleep faster-14.8 minutes, on average-but the difference wasn't significant compared with placebo.
  • Total sleep time was also increased. Patients taking placebo slept 419.7 minutes, on average, compared with 436.8 minutes for the 8-mg dose and 433.1 minutes for the 16-mg dose. The differences from placebo were significant at P=0.009 and P=0.043, respectively.

The increased efficacy of the lower dose implies, Dr. Zammit said, that "there does not appear to be a dose-response relationship."

The morning after the lab stay, the researchers examined the participants using the standard Digit Symbol Substitution test, memory tests for immediate and delayed recall, and visual analog scales to measure mood and feeling. "There was no evidence of next-day impairment," compared to placebo, Dr. Zammit said.

Adverse effects were uncommon and roughly the same in all three arms of the study, the researchers found. Event rates were 12.4%, 13.3%, and 6.4% for placebo, 8-mg, and 16-mg groups, respectively. There were no clinically meaningful changes in any laboratory value, vital sign, or electrocardiogram result.

The most common side effect was somnolence, reported by two placebo patients and three each in the two active treatment arms.

"This is an important therapeutic," Dr. Zammit said, "because it is an unscheduled therapeutic, which provides a sleep-producing effect without sedation or next-day residual effects."