Study Demonstrated ROZEREM(TM) (ramelteon) Does Not Affect Middle-of-the-Night Balance In Older Adults With Insomnia

Article Date: 14 Jun 2007 - 0:00 PDT
http://www.medicalnewstoday.com/medi...4121&nfid=crss

Two studies presented today¨ demonstrated that ROZEREM did not affect body sway at peak plasma levels, nor did it impair middle-of-the-night balance, mobility or memory performance in patients who suffer from chronic insomnia. The results of the studies were presented at the 21st Annual Meeting of the Associated Professional Sleep Societies (APSS).

"These data are important because they show that ROZEREM may be a safe sleep medication for the many older adults who worry about their balance when they need to get up in the middle of the night. These studies also showed that the patients' memories were not affected by ROZEREM the next morning," said Gary Zammit, PhD, director, Sleep Disorders Institute, New York.

ROZEREM works differently from other prescription sleep medications. It specifically targets an area of the brain believed to be involved in the regulation of the body's normal sleep-wake cycle. It is the first prescription sleep medication that is not a controlled substance, and has shown no evidence of abuse or dependence in clinical studies.

ROZEREM Study Design 1: Effect on Body Sway

A total of 275 adults with chronic insomnia received ROZEREM 8 mg, zopiclone 7.5 mg or placebo in a 28-night double-blind treatment period. The primary endpoint was calculated area of center of pressure (COP), in cm2, recorded on the balance platform with eyes open. Zopiclone (Imovane(R) and Zimovane(R)) was used as a positive control. On night 14, patients were given a balance test one-and-a-half hours before dosing. Patients were then given their randomized medications and went to sleep. Approximately two hours after they had taken their treatments, the patients were awakened to take the balance test once again.

Results showed that at the time of predicted near-peak plasma levels, the effect of ROZEREM on body sway was no different from placebo. However, the positive control, zopiclone, did show a statistically significant difference versus placebo at near-peak plasma levels, indicating impairment in body sway. Specific findings showed that the mean log of COP post-dose for placebo was 1.617 cm2 and for ROZEREM 1.497 cm2, (P=0.532). For zopiclone the mean log of COP after dosage was 3.539 cm2, (P<0.001) compared to placebo.

ROZEREM Study Design 2: Middle-of-the-Night Balance, Mobility or Memory Performance

This study evaluated the effects of ROZEREM versus placebo on middle-of- the-night balance, mobility and memory performance in older adults with chronic insomnia, with zolpidem as a positive control. A total of 33 adults age 65 or older with chronic insomnia received ROZEREM 8 mg, zolpidem 10 mg or placebo 30 minutes before bedtime for one night each in this double-blind, placebo-controlled study. Patients were awakened two hours after they were given medication to evaluate standing balance, turning speed and stability, memory and adverse events. The primary endpoint was balance as assessed by NeuroCom EquiTest Sensory Organization Test (SOT) score two hours after dosage. An SOT objectively identifies abnormalities in patients' use of the three sensory systems that contribute to postural control.

Results found that compared to placebo, ROZEREM did not impair middle-of- the-night balance, mobility or memory performance in older adults with chronic insomnia, relative to the positive control zolpidem. A significant decrease in mean SOT composite score was observed between zolpidem and placebo (P<0.001), but not between ROZEREM and placebo (P=0.837). As compared to placebo, ROZEREM results showed:

-- No significant increase in turn time and turn sway (P=0.776, P=0.982, respectively)

-- Immediate memory recall did not decline significantly (P=0.683)

As compared to placebo, zolpidem results showed:

-- Significant increase in turn time and turn sway (P<0.001, both)

-- Immediate memory recall declined significantly with zolpidem (P=0.002)

Adverse events were reported in 13 patients with zolpidem and seven patients during placebo and ROZEREM treatment; none were reported as serious.

About ROZEREM

ROZEREM(TM) (ramelteon) is indicated for the treatment of insomnia characterized by difficulty with sleep onset. ROZEREM can be prescribed for long-term use. ROZEREM is the first and only prescription sleep medication that has shown no evidence of abuse or dependence in clinical studies, and has not been designated as a controlled substance. With the exception of ROZEREM, all other prescription medications indicated for insomnia are classified as Schedule IV controlled substances by the U.S. Drug Enforcement Administration. ROZEREM has a unique therapeutic mechanism of action that selectively targets two receptors located in the brain's suprachiasmatic nucleus (SCN). The SCN is known as the body's "master clock" because it regulates the sleep-wake cycle.

ROZEREM is not a controlled substance. A clinical abuse liability study showed no differences indicative of abuse potential between ROZEREM and placebo at doses up to 20 times the recommended dose (N=14). Three 35-day insomnia studies showed no evidence of rebound insomnia or withdrawal symptoms with ROZEREM compared to placebo (N=2082).

Important Safety Information

ROZEREM should not be used in patients with hypersensitivity to any components of the formulation, severe hepatic impairment, or in combination with fluvoxamine. Failure of insomnia to remit after a reasonable period of time should be medically evaluated, as this may be the result of an unrecognized underlying medical disorder. Hypnotics should be administered with caution to patients exhibiting signs and symptoms of depression.

ROZEREM has not been studied in patients with severe sleep apnea, severe COPD, or in children or adolescents. The effects in these populations are unknown. Avoid taking ROZEREM with alcohol. ROZEREM has been associated with decreased testosterone levels and increased prolactin levels. Health professionals should be mindful of any unexplained symptoms possibly associated with such changes in these hormone levels. ROZEREM should not be taken with or immediately after a high-fat meal. ROZEREM should be taken within 30 minutes before going to bed and activities confined to preparing for bed.

The most common adverse events seen with ROZEREM that had at least a 2% incidence difference from placebo were somnolence, dizziness, and fatigue.

For complete Prescribing Information, visit http://www.ROZEREM.com.

redline.jpg

New Study Suggests No Significant Impairment in Middle-of-the-Night Balance, Mobility or Memory in Older Adults Using Ramelteon

Takeda Phamaceuticals North America
http://www.tpna.com/prdetail.asp?articleid=136

San Diego, CA May 22, 2007 – A new study presented today showed that ramelteon did not impair middle-of-the-night balance, mobility or memory performance in older adults with insomnia, relative to placebo. This study also demonstrated, as in previous studies, that patients treated with zolpidem did have impaired performances on these measures, as compared to placebo. The results of this double-blind, placebo-controlled trial were presented in a poster at the American Psychiatric Association 2007 Annual Meeting.

“These data are important because they indicate that ramelteon is a safe sleep medication for patients, especially older adults, concerned about being impaired in the middle of the night,” said Gary Zammit, PhD, Director, Sleep Disorders Institute, New York. “Many older adults have concerns about their mobility should they get out of bed in the middle of the night for any reason, such as the need to use the bathroom or even react to an emergency. This study showed that when taking ramelteon, balance and mobility were not significantly affected.”

Study Design
A total of 33 adults age 65 or older who suffered from insomnia at least three nights per week for over three months received ramelteon 8 mg, zolpidem 10 mg or placebo 30 minutes before bedtime for one night each in a single-dose, three-period crossover study. Patients were awakened two hours after they were given medication to evaluate standing balance, turning speed and stability, memory and adverse events. The primary endpoint was balance as assessed by NeuroCom EquiTest Sensory Organization Test score (SOT) two hours after dosage.

An SOT protocol objectively identifies abnormalities in patients’ use of the three sensory systems that contribute to postural control: somatosensory (perception of sensory stimuli from the skin and internal organs), visual and vestibular (balance system having to do with the auditory organ). The composite score of each individual sensory test characterizes the overall level of a person’s performance.

Results found that compared to placebo, a significant decrease in SOT composite score was observed with zolpidem (P<0.001), but not with ramelteon (P=0.837). Additional results showed:

• Significant increase in turn time and turn sway versus placebo was seen with zolpidem (P<0.001, both), but not with ramelteon (P=0.776, P=0.982, respectively).
• Immediate memory recall declined significantly with zolpidem (P=0.002), but not with ramelteon (P=0.683).
• Adverse events were reported in 13 patients with zolpidem and seven patients each during placebo and ramelteon treatment; none were noted as serious.
“This study contributes to the growing body of data showing that ramelteon is a safe option for older adults suffering from insomnia characterized by difficulty with sleep onset,” said Zammit. “The trial will also help physicians better understand the unique and differentiating mechanism of action of ramelteon and its potential benefits when making appropriate prescribing decisions for their patients.”

About Ramelteon
Ramelteon is indicated for the treatment of insomnia characterized by difficulty with sleep onset. Ramelteon can be prescribed for long-term use. Ramelteon is the first and only prescription sleep medication that has shown no evidence of abuse or dependence in clinical studies,* and has not been designated as a controlled substance. With the exception of ramelteon, all other prescription medications indicated for insomnia are classified as Schedule IV controlled substances by the U.S. Drug Enforcement Administration. Ramelteon has a unique therapeutic mechanism of action that selectively targets two receptors located in the brain’s suprachiasmatic nucleus (SCN). The SCN is known as the body’s “master clock” because it regulates the sleep-wake cycle.

*Ramelteon is not a controlled substance. A clinical abuse liability study showed no differences indicative of abuse potential between ramelteon and placebo at doses up to 20 times the recommended dose (N=14). Three 35-day insomnia studies showed no evidence of rebound insomnia or withdrawal symptoms with ramelteon compared to placebo (N=2082).

Important Safety Information
Ramelteon should not be used in patients with hypersensitivity to any components of the formulation, severe hepatic impairment, or in combination with fluvoxamine. Failure of insomnia to remit after a reasonable period of time should be medically evaluated, as this may be the result of an unrecognized underlying medical disorder. Hypnotics should be administered with caution to patients exhibiting signs and symptoms of depression.

Ramelteon has not been studied in patients with severe sleep apnea, severe COPD, or in children or adolescents. The effects in these populations are unknown. Avoid taking ramelteon with alcohol.

Ramelteon has been associated with decreased testosterone levels and increased prolactin levels. Health professionals should be mindful of any unexplained symptoms possibly associated with such changes in these hormone levels. Ramelteon should not be taken with or immediately after a high-fat meal. Ramelteon should be taken within 30 minutes before going to bed and activities confined to preparing for bed.

The most common adverse events seen with ramelteon that had at least a 2% incidence difference from placebo were somnolence, dizziness, and fatigue.

For complete Prescribing Information, visit www.ROZEREM.com .