Efficacy of Ramelteon on Speeding Up Sleep in Subjects With Delayed Sleep Phase Syndrome - Full Text View

Sponsored by:	Takeda Global Research & Development Center, Inc.
Information provided by:	Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier:	NCT00593736

Purpose

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.

Condition	Intervention	Phase
Sleep Disorders, Circadian Rhythm	Drug: TAK-375 Drug: Placebo	Phase II

MedlinePlus related topics: Sleep Disorders

Drug Information available for: Ramelteon

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	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)

Further study details as provided by Takeda Global Research & Development Center, Inc.:

Primary Outcome Measures:

Average latency to persistent sleep measured by Polysomnography. [ Time Frame: Nights 6 and 7 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Latency to Persistent Sleep over a 2-Night Average measured by Polysomnography [ Time Frame: Nights 6 and 7; Nights 13 and 14. ] [ Designated as safety issue: No ]
Total Sleep Time over a 2-Night Average measured by Polysomnography [ Time Frame: Nights 6 and 7; Nights 13 and 14. ] [ Designated as safety issue: No ]
Sleep Efficiency over a 2-Night Average measured by Polysomnography [ Time Frame: Nights 6 and 7; Nights 13 and 14. ] [ Designated as safety issue: No ]
Wake Time after Sleep Onset over a 2-Night Average measured by Polysomnography [ Time Frame: Nights 6 and 7; Nights 13 and 14. ] [ Designated as safety issue: No ]
Number of Awakenings over a 2-Night Average measured by Polysomnography [ Time Frame: Nights 6 and 7; Nights 13 and 14. ] [ Designated as safety issue: No ]
Total Wake Time over a 2-Night Average measured by Polysomnography [ Time Frame: Nights 6 and 7; Nights 13 and 14. ] [ Designated as safety issue: No ]
Sleep time and wake time over a 2-Night Average measured by Polysomnography [ Time Frame: Nights 6 and 7; Nights 13 and 14. ] [ Designated as safety issue: No ]
Total Sleep Time measured by Actigraphy [ Time Frame: Nights 6 and 7; Nights 13 and 14. ] [ Designated as safety issue: No ]
Sleep Efficiency measured by Actigraphy [ Time Frame: Nights 6 and 7; Nights 13 and 14. ] [ Designated as safety issue: No ]
Wake Time during sleep interval measured by Actigraphy [ Time Frame: Nights 6 and 7; Nights 13 and 14. ] [ Designated as safety issue: No ]
Wake Bouts measured by Actigraphy [ Time Frame: Nights 6 and 7; Nights 13 and 14. ] [ Designated as safety issue: No ]
Sleep Latency measured by Actigraphy [ Time Frame: Nights 6 and 7; Nights 13 and 14. ] [ Designated as safety issue: No ]
Sleep Time measured by Actigraphy [ Time Frame: Nights 6 and 7; Nights 13 and 14. ] [ Designated as safety issue: No ]
Wake Time measured by Actigraphy [ Time Frame: Nights 6 and 7; Nights 13 and 14. ] [ Designated as safety issue: No ]
Subjective Sleep Latency measured by a Post Sleep Questionnaire [ Time Frame: Nights 6 and 7; Nights 13 and 14. ] [ Designated as safety issue: No ]
Subjective Total Sleep Time measured by a Post Sleep Questionnaire [ Time Frame: Nights 6 and 7; Nights 13 and 14. ] [ Designated as safety issue: No ]
Subjective Wake time After Sleep Onset measured by a Post Sleep Questionnaire [ Time Frame: Nights 6 and 7; Nights 13 and 14. ] [ Designated as safety issue: No ]
Subjective Number of Awakenings measured by a Post Sleep Questionnaire [ Time Frame: Nights 6 and 7; Nights 13 and 14. ] [ Designated as safety issue: No ]
Sleep Quality measured by a Post Sleep Questionnaire [ Time Frame: Nights 6 and 7; Nights 13 and 14. ] [ Designated as safety issue: No ]
Sleep Time measured by a Post Sleep Questionnaire [ Time Frame: Nights 6 and 7; Nights 13 and 14. ] [ Designated as safety issue: No ]
Getting up in the Morning measured by a Post Sleep Questionnaire [ Time Frame: Nights 6 and 7; Nights 13 and 14. ] [ Designated as safety issue: No ]
Ability to Concentrate in the Morning measured by a Post Sleep Questionnaire [ Time Frame: Nights 6 and 7; Nights 13 and 14. ] [ Designated as safety issue: No ]
Level of Alertness measured by a Post Sleep Questionnaire [ Time Frame: Nights 6 and 7; Nights 13 and 14. ] [ Designated as safety issue: No ]
The area under the concentration-time curve of Melatonin [ Time Frame: Days 15 and 16. ] [ Designated as safety issue: No ]
The average maximum concentration of Melatonin [ Time Frame: Days 15 and 16. ] [ Designated as safety issue: No ]
The time of Dim Light Melatonin Secretion Onset of Melatonin [ Time Frame: Visits 4 and 8. ] [ Designated as safety issue: No ]
The time of Dim Light Melatonin Secretion Offset of Melatonin [ Time Frame: Visits 4 and 8. ] [ Designated as safety issue: No ]
The total duration of secretion of Melatonin [ Time Frame: Days 15 and 16. ] [ Designated as safety issue: No ]
Next morning residual effects assessments of Psychomotor and cognitive function via Digit Symbol Substitution Test (DSST). [ Time Frame: Nights 6 and 7; Nights 13 and 14. ] [ Designated as safety issue: No ]
Next morning residual effects assessments of Psychomotor and cognitive function via Memory Recall Test (MRT). [ Time Frame: Nights 6 and 7; Nights 13 and 14. ] [ Designated as safety issue: No ]
Visual Analogue Scale (VAS) for mood and feelings, level of alertness, and ability to concentrate. [ Time Frame: Nights 6 and 7; Nights 13 and 14. ] [ Designated as safety issue: No ]

Enrollment:	132
Study Start Date:	October 2007
Study Completion Date:	May 2008
Primary Completion Date:	May 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1.: Experimental	Drug: TAK-375 TAK-375 1 mg, tablets, orally, once daily for up to two weeks.
2: Experimental	Drug: TAK-375 TAK-375 4 mg, tablets, orally, once daily for up to two weeks.
3: Experimental	Drug: TAK-375 TAK-375 8 mg, tablets, orally, once daily for up to two weeks.
4: Placebo Comparator	Drug: Placebo TAK-375 placebo-matching tablets, orally, once daily for up to two weeks.

Detailed Description:

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 MT1 and 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 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
- OTC 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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00593736

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Sponsors and Collaborators

Takeda Global Research & Development Center, Inc.

Investigators

Study Director:

Medical Director Clinical Science

Takeda Global Research & Development Center, Inc.

More Information

Rozerem Package Insert This link exits the ClinicalTrials.gov site

FDA Safety Alerts and Recalls This link exits the ClinicalTrials.gov site

Responsible Party:	Takeda Global Research & Development Center, Inc. ( Sr VP, Clinical Science )
Study ID Numbers:	01-04-TL-375-044
Study First Received:	January 2, 2008
Last Updated:	December 20, 2008
ClinicalTrials.gov Identifier:	NCT00593736
Health Authority:	United States: Food and Drug Administration

Keywords provided by Takeda Global Research & Development Center, Inc.:

Delayed sleep phase syndrome; drug therapy

Study placed in the following topic categories:

Signs and Symptoms
Sleep Disorders, Circadian Rhythm
Mental Disorders
Neurologic Manifestations
Disorders of Environmental Origin

Dyssomnias
Sleep Disorders
Occupational Diseases
Chronobiology Disorders

Additional relevant MeSH terms:

Pathologic Processes
Disease
Syndrome
Nervous System Diseases

ClinicalTrials.gov processed this record on January 16, 2009