Safety and Efficacy Study of Ramelteon in Subjects With Chronic Insomnia

• Status: Completed
• Trial end date: 2008-03-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to determine the safety and efficacy of 4 mg of Ramelteon, once daily (QD), in subjects with chronic insomnia.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Takeda

Criteria

Inclusion Criteria:

• A female subject of childbearing potential who is sexually active agrees to use adequate contraception from Screening throughout the duration of the study.

• Has a body mass index between 18 and 34, inclusive.

• Based on sleep history, the subject has had chronic insomnia for at least 3 months, as defined by the following:

• The predominant complaint is difficulty initiating or maintaining sleep, or non-restorative sleep, for at least 3 months.

• The sleep disturbance (or associated daytime fatigue) causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.

• The sleep disturbance does not occur exclusively during the course of narcolepsy, breathing-related sleep disorder, circadian rhythm sleep disorder, or parasomnia.

• The disturbance does not occur exclusively during the course of another mental disorder (eg, major depressive disorder, generalized anxiety disorder, delirium).

• The disturbance is not due to the direct physiological effects of a substance or a general medical condition.

• Based on sleep history, the subject reports a history of subjective sleep latency ≥45 minutes and a subjective total sleep time ≤6.5 hours for at least 3 months.

• Based on sleep history, the subject's habitual bedtime is between 10:00 PM and 1:00 AM.

• On at least 3 of the first 5 nights of single blind run-in placebo treatment, the subject must have an subjective sleep latency of ≥45 minutes and a subjective total sleep time of <6.5 hours.

• The difference of the average subjective sleep latency from first 3 nights of data in the first week of single-blind run-in to the average of the last 3 nights of data in the first week of single-blind run-in must be ≤30 minutes.

• The difference of the average subjective sleep latency from first 3 nights of data in the first week of single-blind run-in to the average of the last 3 nights of data in the second week of single-blind run-in must be ≤30 minutes.

• The difference of the average subjective sleep latency from first 3 nights of data in the first week of single-blind run-in to the average of the last 3 nights of data in the third week of single-blind run-in must be ≤30 minutes.

• Is willing to have a fixed bedtime and agrees to go to bed within ± 30 minutes of the habitual bedtime during the entire study, exceptions will be allowed at weekends that are not within 2 days of a polysomnography visit.

• Has consistent access to a touch-tone phone and is willing to complete all telephone questionnaires within 60 minutes of wake time each morning throughout the entire duration of the study.

• Is willing to remain in bed for at least 6.5 hours each night during the entire study.

• Based on sleep history, the subject normally uses pharmacologic assistance to sleep 0 to 4 (maximum allowable) times per week in the last 3 months. Subjects must agree to discontinue the use of all sleep aids beginning 1 week prior to the first dose of single-blind study medication and throughout the entire duration of the study.

• The subject must complete the post-sleep questionnaire morning questionnaire on at least 5 of 7 mornings for all 3 weeks of single-blind run-in.

• Has a mean latency to persistent sleep of ≥20 minutes on 2 consecutive screening nights, with neither night less than 15 minutes, via polysomnography screening assessment during the single-blind placebo run-in period.

Exclusion Criteria:

• Has a known hypersensitivity to ramelteon or related compounds, including melatonin.

• Has participated in a study involving ramelteon within 6 months of initial Screening Visit.

• Has participated in any other investigational study and/or taken any investigational drug within 30 days or 5 half-lives (whichever is longer) prior to the first night of single-blind study medication.

• Has sleep schedule changes required by employment (eg, shift worker) within 3 months prior to the first night of single-blind study medication, or has flown across greater than 3 time zones within 7 days prior to Screening.

• Has participated in a weight loss program or has substantially altered his or her exercise routine within 30 days prior to the first night of single-blind study medication.

• Has ever had a history of seizures, sleep apnea, restless leg syndrome, periodic leg movements during sleep, chronic obstructive pulmonary disease, fibromyalgia, schizophrenia, bipolar disorder, mental retardation or a cognitive disorder.

• Has a history of psychiatric disorder (including anxiety or depression) within the past 12 months.

• Has a history of drug addiction or alcohol abuse and/or regularly consumes 4 or more alcoholic drinks per day within the past 12 months, as defined in Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised.

• Has a current significant neurological (including cognitive and psychiatric disorders), hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, hematological, or metabolic disease, unless currently controlled and stable with protocol-allowed medication 30 days prior to the first night of single blind study medication.

• The subject uses tobacco products (including nicotine gum and patch) during nightly awakenings.

• The subject has any clinically important abnormal finding as determined by a medical history, physical examination, electrocardiogram, or clinical laboratory tests, as determined by the investigator.

• The subject 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

• Central nervous system active drugs (including herbal)

• Hypnotics

• Narcotic analgesics

• Antidepressants

• Beta-blockers

• Anticonvulsants

• Systemic steroids

• Sedating H1 antihistamines

• Respiratory stimulants

• Muscle relaxants

• Sedatives

• Antipsychotics

• Sedating decongestants

• Kava-kava

• St. John's wort

• Ginkgo biloba

• Over-the counter and prescription stimulants, diet aids and sleep aids

• Drugs that are known or are suspected to significantly inhibit CYP450

• Melatonin

• Has a positive urine drug screen for an illegal substance at the initial Screening Visit.

• Has a positive urine drug screen at polysomnography screening or a positive alcohol breathalyzer test at polysomnography screening or randomization.

• Exhibits a placebo response during the single-blind placebo run-in period. A placebo response is defined as having:

• a difference in average subjective sleep latency >30 minutes from first 3 nights of data in the first week of single-blind run-in to the average of the last 3 nights of data in the first week of single-blind run-in.

• a difference in average subjective sleep latency >30 minutes from first 3 nights of data in the first week of single-blind run-in to the average of the last 3 nights of data in the second week of single-blind run-in.

• a difference in average subjective sleep latency >30 minutes from first 3 nights of data in the first week of single-blind run-in to the average of the last 3 nights of data in the third week of single-blind run-in.

• Has periodic leg movements during sleep with arousal index (per hour of sleep) >10 as seen on polysomnography on the first night of polysomnography screening.

• 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 to complete the study.