Efficacy of Ramelteon on Speeding Up Sleep in Subjects With Delayed Sleep Phase Syndrome
Condition: Sleep Disorders, Circadian Rhythm
MeSH terms: Sleep Wake Disorders; Sleep Disorders, Circadian Rhythm
Intervention: Ramelteon; Ramelteon; Ramelteon; Placebo
Intervention description: Ramelteon 1 mg, tablets, orally, once daily for up to two weeks.; Ramelteon 4 mg, tablets, orally, once daily for up to two weeks.; Ramelteon 8 mg, tablets, orally, once daily for up to two weeks.; Ramelteon placebo-matching tablets, orally, once daily for up to two weeks.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 132.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Delayed sleep phase syndrome; drug therapy

Summary:

      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.
    

Eligibility criteria:

        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:

               -  During Polysomnography screening nights when the subject goes to bed at their
                  desired sleep time or

               -  The average of total wake time

          -  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:

               -  Anxiolytics

               -  Hypnotics

               -  Antidepressants

               -  Anticonvulsants

               -  Sedating H1 antihistamines

               -  Systemic steroids

               -  Respiratory stimulants

               -  Decongestants

               -  Antipsychotics

               -  Muscle relaxants

               -  Over-the-counter and prescription diet aids

               -  Narcotic analgesics

               -  Beta Blockers

               -  St. John's wort

               -  Kava kava

               -  Ginkgo biloba

               -  Modafinil

               -  Coumadin

               -  Heparin

               -  Melatonin and all other drugs or supplements known to affect sleep/wake function
                  will be prohibited within 1 week of the first dose of study medication and during
                  the entire study.

          -  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:

               -  Affect sleep/wake function

               -  Prohibit the subject from completing the study, or

               -  Not be in the best interest of the subject.

          -  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.