Ramelteon (ROZEREM) in the Treatment of Sleep Disturbances Associated With Parkinson's Disease

It is well established that sleep disturbances are common in patients with neurodegenerative
disorders such as Parkinson's disease. Together with psychosis and other behavioral
abnormalities they contribute to the stress, anxiety and cognitive decline of patients,
caregiver burnout and depression, as well as health care provider frustration. The mechanisms
of the sleep disturbances in these conditions are still poorly understood and no rational or
effective treatments have been proposed. Recent data from a study of ramelteon in the elderly
showed a striking ability of this compound to improve quality of sleep disturbances in
Parkinson's disease.

Objectives of this study are:

- To examine the effects of ramelteon on the quality of sleep using sleep evaluation
instruments (SDQ-Sleep Disorder Questionnaire and Neuropsychiatric Inventory with
Caregiver Distress (NPI-D) Sleep Behavior Subscale administered to the patient and/or
their bed partner.

- To examine the effects of ramelteon on daytime sleepiness and memory using Epworth
Sleepiness Scale (ESS) and Hopkins Verbal Learning Test (HVLT).

- To examine the effects of ramelteon on the sleep/wake cycle and day/night activity
patterns over a prolonged period of time (1 week) using a motion logger (continuous
motor activity recording device) and computerized data analysis.

- To examine the effects of ramelteon on sleep architecture in a sample of patients with
confirmed sleep disturbance, before and after ramelteon treatment by using
polysomnography.

Inclusion Criteria:

- 45-85 years of age and living in the community

- Male or female of non-child bearing potentials (non-child bearing is defined as at
lease 6 months post-menopause or surgically sterile)

- Must have a diagnosis of Parkinson's disease

- Must have complaints of sleep disturbance

Exclusion Criteria:

- Patients with diagnosis of or those meeting DSM-IV criteria for major depression,
schizophrenia or schizoaffective disorder, bipolar disorder, substance abuse disorder,
other mental illness that is known to contribute to sleep disturbance, epilepsy, other
medical conditions that are known to cause or contribute to sleep disturbances

- Patients currently using melatonin or ramelteon, hypnotics, benzodiazepines,
antidepressants, blood-brain barrier permeable beta blockers, steroids, antipsychotics

- Patients with clinically significant blood or urine abnormalities

- Patients who have taken any investigational drug less than 1 month prior to the
baseline visit

- Patients with multiple concomitant disorders with or without medications thought to
produce sleep disturbances

- Patients with pre-existing sleep disturbances unrelated to Parkinson's disease

- Patients with severe hepatic impairment (Child-Pugh Class C)

- Patients with severe COPD (those with elevated pCO2 levels or those needing nocturnal
oxygen therapy

- Patients with severe sleep apnea

- Patients who have sensitivity to ramelteon or any constituents of the Rozerem
preparation

- Patients taking rifampin or potent inducers of CYP1A2, CYP3A4, CYP2C9 (ketoconazole,
fluconazole)

- Patients living in a nursing home. Those living in assisted living facilities and
board and care facilities may be included

- Patients unable to comply with the study protocol