Safety of Ramelteon in Subjects With Mild to Moderate Obstructive Sleep Apnea

• Status: Completed
• Trial end date: 2003-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to assess the safety of ramelteon, once daily (QD), in individuals with obstructive sleep apnea.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Takeda

Criteria

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