Status:

COMPLETED

Safety and Efficacy Study of Ramelteon in Subjects With Chronic Insomnia

Lead Sponsor:

Takeda

Conditions:

Sleep Initiation and Maintenance Disorders

Eligibility:

All Genders

18-64 years

Phase:

PHASE3

Brief 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.

Detailed Description

In the western world, there are several people affected by chronic insomnia. Numerous studies estimate that 30% to 40% of the general population is affected at some time in their lives with a form of ...

Eligibility Criteria

Inclusion

  • 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

  • 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.

Key Trial Info

Start Date :

August 1 2007

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

March 1 2008

Estimated Enrollment :

259 Patients enrolled

Trial Details

Trial ID

NCT00756002

Start Date

August 1 2007

End Date

March 1 2008

Last Update

June 2 2010

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