Long-Term Efficacy and Safety of Ramelteon in Adults With Chronic Insomnia.

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00247390
• Date of registration: 28/10/2005
• Prospective Registration: No
• Primary sponsor: Takeda
• Public title: Long-Term Efficacy and Safety of Ramelteon in Adults With Chronic Insomnia.
• Scientific title: A Randomised, Double-blind, Placebo-controlled Study to Determine the Long-term Efficacy and Safety of Ramelteon in Adults With Chronic Insomnia.
• Date of first enrolment: July 2005
• Target sample size: 451
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00247390
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
• Phase: Phase 3

Countries of recruitment

Australia, Belgium, Czech Republic, Finland, France, Germany, Italy, Russian Federation, United States

Contacts

• Name: Medical Director Clinical Science
• Affiliation: Takeda

Key inclusion & exclusion 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.

- Body mass index between 18 and 34, inclusive.

- Based on sleep history, has had chronic insomnia for at least 3 months.

- Based on sleep history, reports a subjective sleep latency greater than or equal to
45 min and a subjective total sleep time less than or equal to 6.5 hours.

- Based on sleep history, habitual bedtime is between 10:00 PM and 1:00 AM.

- Mean latency to persistent sleep of greater than 20 minutes on two consecutive
screening nights with neither night less than 15 minutes. Also, a mean of 60 minutes
of wake time during the 480 minutes in bed across two nights with no night less than
45 minutes.

- Based on sleep history, normally uses pharmacological assistance to sleep 0 to 4
times per week in the last 3 months.

Exclusion Criteria

- Known hypersensitivity to ramelteon or related compounds, including melatonin, and
melatonin related compounds.

- Participated in any other investigational study and/or taken any investigational drug
within 30 days or five half-lives prior to the first dose of single-blind study
medication, whichever is longer.

- Sleep schedule changes required by employment (eg, shift worker) within three months
prior to the administration of single-blind study medication.

- Flown across greater than three time zones within 7 days prior to or during
screening.

- Participated in a weight loss program or has substantially altered their exercise
routine within 30 days prior to the administration of single-blind study medication.

- Has ever had a history of seizures, sleep apnea, restless leg syndrome, periodic leg
movement syndrome, chronic obstructive pulmonary disease or fibromyalgia.

- History of psychiatric disorder within the past 6 months.

- History of alcohol abuse within the past 12 months, as defined in Diagnostic &
Statistical Manual of Mental Disorders, 4th Edition Revised, or regularly consumes
more than 14 alcoholic drinks per week, or consumed any alcoholic drinks within 24
hours of any polysomnogram visits.

- History of drug abuse within the past 12 months, as defined in Diagnostic &
Statistical Manual of Mental Disorders, 4th Edition Revised.

- Current significant hepatic, renal, endocrine, cardiovascular, gastrointestinal,
pulmonary, hematologic, neurological, or metabolic disease, unless currently
controlled and stable with protocol-allowed medication, within 30 days prior to the
first night of single-blind study medication.

- Apnea hypopnea index (per hour of sleep) greater than 10 as seen on the first
polysomnogram screening night.

- Periodic Leg Movement Syndrome with arousal index (per hour of sleep) greater than 10
as seen on the first polysomnogram screening night.

- Positive urine drug screen at Screening Visit 1 or any of the polysomnogram
assessment visits.

- Positive breathalyzer test on any of the polysomnogram assessment visits.

- Uses tobacco products (including nicotine gum and patch) or any other products that
may interfere with the sleep wake cycle during nightly awakenings.

- Used any central nervous system medication or other drugs or supplements known to
affect sleep/wake function within 1 week (or 5 half lives of the drug, whichever is
longer) prior to the administration of single-blind study medication. These
medications must not have been used to treat psychiatric disorders.

- Intends to continue taking any disallowed medication or any prescription medication
or over the counter medication that is known to affect the sleep/wake function or
otherwise interfere with evaluation of the study medication. The subject must report
all prescription and over the counter medications taken in the three weeks prior to
screening.

- Is required to take or continues taking any disallowed medication, prescription
medication, herbal treatment or over-the counter medication that may interfere with
evaluation of the study medication, including:

- Anxiolytics

- Sedatives

- Hypnotics

- CNS active drugs (including herbal)

- Antidepressants

- Narcotic analgesics

- Anticonvulsants

- Beta blockers

- Sedating H1 antihistamines

- St. John's Wort

- Systemic steroids

- Kava-kava

- Respiratory stimulants

- Ginkgo-biloba

- Decongestants

- Over-the-counter and prescription stimulants

- Antipsychotics

- Over-the-counter and prescription diet aids

- Muscle Relaxants

- Melatonin and all other drugs or supplements known to affect sleep/wake function

- Any additional condition(s) that in the Investigator's opinion would

- affect sleep/wake function

- prohibit the subject from completing the study

- indicate that continuation in the study would not be in the best interests of
the subject.

- History of hepatitis B or hepatitis C.



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Chronic Insomnia

Intervention(s)

Drug: Ramelteon

Drug: Placebo

Primary Outcome(s)

Mean change in Latency to Persistent Sleep of 2-night polysomnogram. [Time Frame: Months 3 and 6 or Final Visit]

Secondary Outcome(s)

Total Sleep Time in stage 1 sleep as determined by polysomnogram. [Time Frame: Week 1 and Months 1, 3, 5 and 6 or Final Visit]

Total Sleep Time in stage 2 non-rapid eye movement (NREM) sleep as determined by polysomnogram. [Time Frame: Week 1 and Months 1, 3, 5 and 6 or Final Visit]

Latency to Rapid Eye Movement as determined by polysomnogram. [Time Frame: Week 1 and Months 1, 3, 5 and 6 or Final Visit]

Total Sleep Time in stage 3/4 non-rapid eye movement (NREM) sleep as determined by polysomnogram. [Time Frame: Week 1 and Months 1, 3, 5 and 6 or Final Visit]

Mean change in Subjective Total Sleep Time by postsleep questionnaire on 2 nights over 6 months. [Time Frame: Week 1 and Months 1, 3, 5 and 6 or Final Visit]

Mean change in Total Sleep Time from polysomnogram, on 2 nights over 6 months. [Time Frame: Week 1 and Months 1, 3, 5 and 6 or Final Visit]

Total Sleep Time in rapid eye movement (REM) sleep as determined by polysomnogram. [Time Frame: Week 1 and Months 1, 3, 5 and 6 or Final Visit]

Mean change in Subjective Sleep Latency by postsleep questionnaire on 2 nights over 6 months. [Time Frame: Week 1 and Months 1, 3, 5 and 6 or Final Visit]

Total Sleep Time in stage 1 non-rapid eye movement (NREM) sleep as determined by polysomnogram. [Time Frame: Week 1 and Months 1, 3, 5 and 6 or Final Visit]

Mean change in Subjective Number of Awakenings by postsleep questionnaire. [Time Frame: Week 1 and Months 1, 3, 5 and 6 or Final Visit]

Mean change in Subjective Sleep Quality by postsleep questionnaire. [Time Frame: Week 1 and Months 1, 3, 5 and 6 or Final Visit]

Secondary ID(s)

2004-004351-20

TAK-375-EC302

U1111-1114-3231

Source(s) of Monetary Support

Please refer to primary and secondary sponsors