Efficacy and Safety of Ramelteon Combined With Gabapentin in Treating Patients With Insomnia

• Female patients of childbearing potential must be nonpregnant and nonlactating, and utilizing an acceptable method of contraception.
• Based on sleep history, the subject has had primary insomnia as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised (DSM-IV-TR™) for at least 3 months.
• Based on sleep history, reports a subjective sleep latency greater than or equal to 45 minutes and reports wake time after persistent sleep onset of greater than or equal to 45 minutes.
• Has an average wake time after persistent sleep onset of at least 60 minutes as determined by polysomnography during Screening (Day minus 7 PM through Day minus 5 AM). Wake time after persistent sleep onset must be greater than or equal to 30 minutes each night of polysomnography Screening.
• Reports wake time after persistent sleep onset values of at least 60 minutes on at least 3 of the 7 nights during the single-blind screening period (Day minus 6 AM through Day 1 AM) as determined by post-sleep questionnaire.
• Has an average latency to persistent sleep of at least 20 minutes as determined by polysomnography during Screening (Day minus 7 PM through Day minus 5 AM).
• Based on sleep history, has an habitual bedtime between 9:00 PM and 1:00 AM.
• The subject is willing to have a fixed bedtime and agrees to go to bed within plus or minus 30 minutes of the habitual bedtime during the entire study and agrees to remain in bed for at least 8 hours each night.
• Based on sleep history, has not been using pharmacological assistance to sleep or uses pharmacological assistance no more than 4 times per week during the 3 months prior to Initial Screening.
• Has consistent access to a touch-tone phone and are willing to complete telephone questionnaires twice daily during participation in the study.

Exclusion Criteria:

• Has a known hypersensitivity to gabapentin or its ingredients, ramelteon or related compounds, including melatonin, and 5-hydroxytryptophan.
• Has participated in any other investigational study and/or taken any investigational drug within 30 days prior to the first dose of single-blind study medication.
• Has sleep schedule changes required by employment (eg, shift worker) within 3 months prior to the first dose of single-blind study medication.
• Has flown across greater than 3 time zones within 7 days prior to Initial Screening, or will travel across 2 or more time zones during the course of the study.
• Has participated in a weight loss program or has substantially altered their exercise routine within 30 days prior to the first dose of single-blind study medication.
• Has ever had a history of seizures, sleep apnea, and/or chronic obstructive pulmonary disease.
• Has a history of psychiatric disorder (including anxiety, depression, mental retardation, cognitive disorder, bipolar illness and schizophrenia) within the past 6 months of Initial Screening.
• Has a history of fibromyalgia.
• Has a history of drug addiction or drug abuse within the past 12 months of Initial Screening.
• Has a history of alcohol abuse within the past 12 months, as defined in DSM-IV-TR™ and/or regularly consumes more than 2 alcoholic drinks per day.
• Has a current significant hepatic, endocrine, cardiovascular, gastrointestinal, pulmonary, hematological, metabolic or neurological disorders, unless currently controlled and stable with protocol-allowed medication, within 30 days prior to the first dose of single-blind study medication.
• Has any diagnosed renal impairment within 30 days prior to the first dose of single-blind study medication.
• Has a previous history of cancer, other than basal cell carcinoma, that has not been in remission for at least 5 years prior to the first dose of single-blind study drug.
• Uses tobacco products or any other products that may interfere with the sleep wake cycle during nightly awakenings.

• Is required to take or intends to continue taking any disallowed medication or any prescription medication or over-the counter medication that is known to affect the sleep/wake function or otherwise interfere with evaluation of the study medication, including:

  • Anxiolytics central nervous system active drugs (including herbal)
  • Hypnotics Narcotic analgesics
  • Antidepressants Beta blockers
  • Anticonvulsants St. John's Wort
  • Sedating H1 antihistamines Kava-kava
  • Systemic steroids Ginkgo-biloba
  • Respiratory stimulants over-the counter and prescription stimulants
  • Sedating decongestants over-the counter and prescription diet aids
  • Antipsychotics over-the counter sleep aids
  • Muscle relaxants Antacids
  • Melatonin and all other drugs or supplements known to affect sleep/wake function.
• Has a positive hepatitis panel including anti- hepatitis A virus, hepatitis B surface antigen or anti-hepatitis C virus.
• Has a positive urine drug screen including alcohol at Initial Screening or a positive breathalyzer test at each polysomnography Screening check-in.
• Has an apnea hypopnea index (per hour of sleep) >15 as seen on polysomnography, on the first night of the polysomnography screening.
• Has a history of restless leg syndrome.
• The subject has a body mass index of less than 18 or greater than 34 (weight /height2).

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

  • Affect sleep/wake function
  • Prohibit the subject from completing the study
  • Not be in the best interest of the subject.