Safety and Efficacy of Ramelteon and Doxepin in Subjects With Chronic Insomnia

Exclusion Criteria

• •Has a known hypersensitivity to doxepin or related compounds (tricyclic antidepressants), or 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.
• •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.
• •* Melatonin and all other drugs or supplements known to affect sleep/wake function.
• •Has ever had a history of fibromyalgia, glaucoma, seizures (excluding childhood febrile seizures), sleep apnea, and/or chronic obstructive pulmonary disease.
• •Currently has, or has had a diagnosed history of psychiatric disorder as defined in DSM-IV-TR™ (including anxiety, depression, suicidal ideation, mental retardation, cognitive disorder, bipolar illness and schizophrenia) within the past 6 months of Initial Screening.
• •Has a history of drug addiction or drug abuse as defined in DSM-IV-TR™ 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, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, hematological, metabolic or neurological disorders, or tendency for urinary retention, unless currently controlled and stable with protocol-allowed medication, 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. (This criterion does not apply to subjects with basal cell or Stage 1 squamous cell carcinoma of the skin).
• •Uses tobacco products or any other products that may interfere with the sleep wake cycle during nightly awakenings.
• •Has used any central nervous system medication or other drugs or supplements known to affect sleep/wake function within 1 week (or 5 half lives of the drug, whichever is longer) prior to the administration of single-blind study medication. These medications must not have been used to treat psychiatric disorders.
• •Has used melatonin, or other drugs or supplements known to affect sleep/wake function within 1 week (or 5 half lives of the drug, whichever is longer) prior to the first dose of single-blind study medication.
• •Has any clinically important abnormal finding as determined by a medical history, physical examination, electrocardiogram, or clinical laboratory tests, as determined by the investigator.
• •Has a positive hepatitis panel including anti- hepatitis A virus (only Immunoglobulin M \[IgM\] is exclusionary), hepatitis B surface antigen, or anti- hepatitis C virus.
• •Has a history of human immuno-deficiency virus disease.
• •Has a positive urine drug screen including alcohol at Initial Screening or a positive breathalyzer test at any polysomnography check-in.
• •Has an apnea hypopnea index (per hour of sleep) \>10 (subjects aged 18 to 64) or \>15 (subjects aged 65 to 80) as seen on polysomnography, on the first night of the polysomnography screening.
• •Has periodic leg movement with arousal index (per hour of sleep) \>10 (subjects aged 18 to 64) or \>15 (subjects aged 65 to 80) as seen on polysomnography, on the first night of polysomnography screening.
• •Has a diastolic blood pressure greater than 90 mm Hg or a systolic pressure of greater than 150 mm Hg.
• •The subject has an alanine transaminase level of greater than 3 times the upper limit of normal, active liver disease, or jaundice.
• •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.