Efficacy of Ramelteon in Subjects With Chronic Insomnia

• Participant has participated in an allowed Ramelteon study and has completed all final visit procedures for the previous study within 21 days of the Treatment Initiation Visit for this study.
• Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.
• Investigator believes that participant requires long-term treatment for insomnia.
• Primary insomnia as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised for at least 3 months and a history of daytime complaint(s) associated with disturbed sleep.
• Subjective sleep latency greater than or equal to 45 minutes and a subjective total sleep time less than or equal to 6.5 hours per night for at least 3 nights during the week of the Baseline Lead-in Period.
• Habitual bedtime is between 8:30PM and 12:00AM.
• Body mass index between 18 and 34, inclusive.

Exclusion Criteria

• Known hypersensitivity to Ramelteon or related compounds, including melatonin.
• Participated in any other investigational study, and/or taken any investigational drug within 30 days or five half-lives prior to Day 1 of study medication, whichever is longer. The only exception to this is prior participation in an allowed Ramelteon study.
• Sleep schedule changes required by employment (eg, shift worker) within three months prior to Day 1 of study medication, or has flown across greater than three time zones within seven days prior to screening.
• Participated in a weight loss program or has substantially altered their exercise routine within 30 days prior to Day 1 of study medication.
• Ever had a history of seizures, sleep apnea, chronic obstructive pulmonary disease, restless leg syndrome, schizophrenia, bipolar disorder, mental retardation, or cognitive disorder.
• History of psychiatric disorder (including anxiety or depression) within the past 12 months.
• History of drug addiction or drug abuse with the past 12 months.
• History of alcohol abuse within the past 12 months, as defined in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised and/or regularly consumes 4 or more alcoholic drinks per day.
• Current significant neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, hematologic, or metabolic disease, unless currently controlled and stable with protocol-allowed medication 30 days prior to Day 1 of study medication.
• Uses tobacco products during nightly awakenings.
• Any clinically important abnormal finding as determined by a medical history, physical examination, electrocardiogram, or clinical laboratory tests, as determined by the investigator.
• Positive hepatitis panel.

• Any additional condition(s) that in the Investigator's opinion would:

  • affect sleep/wake function
  • prohibit the subject from completing the study, or
  • not be in the best interest of the subject to participate in the study.
• Morning serum cortisol at the Baseline visit of less than 7.0 micro-g per dl.

• Is required to take or continues taking any disallowed medication, prescription medication, herbal treatment or over-the counter medication, including:

  • Anxiolytics
  • Hypnotics
  • Antidepressants
  • Anticonvulsants
  • Sedating H1 antihistamines
  • Systemic steroids
  • Respiratory stimulants (eg, theophylline)
  • Decongestants
  • Over-the-counter and prescription stimulants
  • Over-the-counter and prescription diet aids
  • Central nervous system active drugs
  • Narcotic analgesics
  • Beta blockers
  • St. John's Wort
  • Kava-kava
  • Gingko biloba
  • Melatonin