Safety of Ramelteon in Subjects With Mild to Moderate Chronic Obstructive Pulmonary Disease

Inclusion Criteria

• 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.
• Clinical history of chronic obstructive pulmonary disease and a confirmatory diagnosis based on pulmonary function tests at screening.
• Moderate: forced expiratory volume in one second/ forced vital capacity less than 70% and forced expiratory volume 135-75% of predicted.
• Post-bronchodilator forced expiratory volume in one second change from baseline of less than 12%.
• Negative chest x-ray at screening, other than findings consistent with mild to moderate chronic obstructive pulmonary disease, within the last 6 months.
• Arterial oxygen saturation during sleep greater than 85% for at least 99% of the recording period, with no arterial oxygen saturation readings less than 80% as assessed by pulse oximetry at polysomnography screening.
• Arterial oxygen saturation during wakefulness greater than 91% (both supine and sitting) as assessed by pulse oximetry at screening.
• Habitual bedtime is between 8:30 p.m. and 12:00 a.m.
• Body mass index between 18 and 34, inclusive.
• Agrees to remain in the study center for three overnight stays.

Exclusion Criteria:

• Known hypersensitivity to ramelteon or related compounds, including melatonin.
• Known hypersensitivity to Ventolin® or related compounds.
• Previously participated in a study involving ramelteon.
• 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.
• Clinical history of acute or chronic respiratory failure, severe chronic obstructive pulmonary disease, or hypercapnia (Partial Pressure of Oxygen in Arterial Blood greater than or equal to45 mmHg).
• History of or currently has right ventricular hypertrophy on electrocardiogram or right heart failure.
• Periodic leg movement with arousal index (per hour of sleep) greater than 20 as seen at polysomnography screening.
• Apnea hypopnea index greater than 15 as seen at polysomnography screening.
• Acute clinically significant illness within 2 weeks or has been hospitalized within 4 weeks of study participation.
• Sleep schedule changes required by employment 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 medications.
• History of seizures, sleep apnea, restless leg syndrome, period limb movement disorder, other known sleep disorders, schizophrenia, bipolar disease, mental retardation, or cognitive disorder.
• History of psychiatric disorder within the past 12 months.
• History of drug addiction or drug abuse within the past 12 months.
• History of alcohol abuse within the past 12 months and/or regularly consumes 4 or more alcoholic drinks per day.
• Unable to discontinue the use of hypnotics for the duration of the study.
• Any clinically important abnormal finding, other than chronic obstructive pulmonary disease, as determined by medical history, physical examination, electrocardiogram, or clinical laboratory tests, as determined by the investigator.
• 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.
• Hematocrit value greater than 55% at screening.
• 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
  • not be in the best interest of the subject

• 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
  • Decongestants
  • Over-the-counter and prescription stimulants
  • Over-the-counter and prescription diet aids
  • Central nervous system active drugs and narcotic analgesics
  • Lipophilic beta blockers
  • Melatonin
  • St. John's Wort
  • Kava-kava
  • Gingko biloba