A Randomized, Double-Blind, Placebo-Controlled, Parallel, Proof of Concept Study to Evaluate the Effectiveness of Ramelteon to Advance the Timing of Sleep in Individuals With Delayed Sleep Phase Syndrome (DSPS)
A Randomized, Double-Blind, Placebo-Controlled, Parallel, Proof of Concept Study to Evaluate the Effectiveness of Ramelteon to Advance the Timing of Sleep in Individuals With Delayed Sleep Phase Syndrome (DSPS)
The purpose of this study is to evaluate the ability of ramelteon, once daily (QD), to advance the timing of sleep in individuals with delayed sleep phase syndrome.
Delayed sleep phase syndrome is the most common circadian disorder in adolescents and most adults with the condition report onset of symptoms during childhood or adolescence. Delayed Sleep Phase Syndrome involves a chronic mismatch between the usual daily schedule required by the individual's environment and his or her circadian sleep wake pattern. Individuals suffering from delayed Sleep Phase Syndrome experience great difficulty when attempting to fall asleep before 1-2 am, if not later, as well as rising at acceptable hours of the morning despite having completely normal sleep architecture and sleep duration. Delayed Sleep Phase Syndrome is a sleep disorder that results from a dysregulation of the circadian sleep-wake rhythm. Delayed Sleep Phase Syndrome is often the cause of severe insomnia and is associated with excessive daytime sleepiness, major depressive disorder and severe disruption of education, work and social functioning. Its major symptom is extreme difficulty initiating sleep at a conventional hour and waking on time in the morning for school or work.
Ramelteon is a selective melatonin type 1 (MT1) and type 2 (MT2) receptor agonist. The purpose of this study is to evaluate the ability of ramelteon to advance the timing of sleep in individuals with delayed sleep phase syndrome. The effect of ramelteon will be analyzed based on collection of information from a post-sleep questionnaire completed by participants, and data collected by polysomnography in a sleep clinic setting. Total participation time involved in this study will be approximately 7 weeks.
Inclusion Criteria:
Females of childbearing potential who is sexually active must agree to use adequate contraception from screening throughout the duration of the study.
Must have a diagnosis of Delayed Sleep Phase Syndrome according to International Classification of Sleep Disorders criteria for at least 3 months.
Based on sleep history, subject's habitual sleep time is more than 3 hours later than the desired sleep time.
Must have had self reported insomnia which is defined per the sleep history as his or her sleep latency of at least 45 minutes when attempting to sleep at desired sleep time required by his or her work or school schedule.
The subjective sleep latency via Post sleep questionnaire during outpatient screening period must be greater than or equal to 45 minutes during every working night or school night provided the subject went to bed at their desired sleep time.
During single blind placebo run-in Polysomnography screening nights, subject is instructed to go to bed at their desired bed time and must demonstrate difficulty in falling asleep based on the following criteria:
Is in good health as determined by a medical and psychiatric history, physical examination, Electrocardiogram, and serum chemistry and hematology.
Is able to complete self-rating scales via interactive voice response system, and has a touch tone phone.
Is willing to comply with study procedures and restrictions with fixed sleep time and wake time during the study and to attend regularly scheduled clinic visits as specified in this protocol.
Has a body mass index is between 18 and 34 kg/m2, inclusive.
Has a negative urine test result for selected substances of abuse (including alcohol).
Has a negative test result for hepatitis B surface antigen and hepatitis C virus antibody or history of human immunodeficiency virus.
Has not used pharmacological sleep assistance for more than 4 times/week during the 3 months prior to Initial Screening.
Must have discontinued use of all pharmacological sleep aids beginning 1 week prior to Visit 2 and for the duration of the trial.
Exclusion Criteria:
Has a known hypersensitivity to ramelteon or related compounds, including melatonin and melatonin-related compounds or 5-hydroxytryptophan.
Has participated in any other investigational study and/or taken any investigational drug within 30 days or 5 half-lives prior to the first dose of study medication, whichever is longer.
Has flown across greater than 3 time zones within the past 3 months prior to administration of study medication.
Has sleep schedule changes required by employment (eg, shift worker) within 3 months prior to the administration of study medication.
Has participated in a weight loss program or has substantially altered their exercise routine within 30 days prior to the administration of study medication.
Has a history of alcohol abuse within the past 12 months, as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, or regularly consumes more than 14 alcoholic drinks per week or consumes any alcoholic drinks within 24 hours of Screening Visit.
Has a history of drug abuse within the past 12 months.
Has a current, clinically significant neurological (including cognitive), hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, hematological, or metabolic disease, as determined by the investigator.
Has a probable current diagnosis of another circadian rhythm disorder or a sleep disorder other than Delayed Sleep Phase Syndrome that is the primary cause of insomnia.
Had an apnea hypopnea index greater than 10 on the first night of Polysomnography Screening.
Has periodic limb movements during sleep with arousal index greater than 10 as seen on the first night of Polysomnography screening only.
Has a positive urine drug screen or breathalyzer test.
Has ever had a history of seizures; sleep apnea, restless leg syndrome, chronic obstructive pulmonary disease, fibromyalgia, or a positive test result for the aforementioned ailments on the screening Polysomnography, schizophrenia, bipolar disorder, mental retardation, or cognitive disorder.
Has a history of psychiatric disorder (including anxiety or depression) within the past 12 months.
Smokes more than 3 cigarettes per day or uses tobacco products during nightly awakenings.
Routinely consumes caffeine including coffee, tea and/or other caffeine-containing beverages or food averaging more than 600 mg of caffeine per day.
Has used any central nervous system drug or other medications, including those used to treat psychiatric disorders, known to affect sleep/wake function within 1 week whichever is longer prior to the administration of single blind study drug.
Used melatonin, or other drugs/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 medication.
Is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:
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, hepatitis B surface antigen or anti- hepatitis C virus.
Has any additional condition(s) that in the investigator's opinion would:
Exhibits a placebo response during single-blinded placebo run in period.
Individuals with a habitual sleep time later than 4:00 am should not be included in the study.
Hallandale Bch, Florida, United States