Efficacy of Ramelteon on Speeding Up Sleep in Subjects With Delayed Sleep Phase Syndrome

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00593736
• Collaborator: (none)
• Enrollment: 132
• Locations: 42
• Arms: 4
• Duration (Months): 7
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Sleep Disorders, Circadian Rhythm	Drug: Ramelteon; Drug: Ramelteon; Drug: Ramelteon; Drug: Placebo	Phase 2

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 melatonin type 1 (MT1) and type 2 (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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 132 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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)
• Study Start Date: Oct 1, 2007
• Actual Primary Completion Date: May 1, 2008
• Actual Study Completion Date: May 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ramelteon 1 mg QD	Drug: Ramelteon; Ramelteon 1 mg, tablets, orally, once daily for up to two weeks.; Other Names: Rozerem™ TAK-375
Experimental: Ramelteon 4 mg QD	Drug: Ramelteon; Ramelteon 4 mg, tablets, orally, once daily for up to two weeks.; Other Names: Rozerem™ TAK-375
Experimental: Ramelteon 8 mg QD	Drug: Ramelteon; Ramelteon 8 mg, tablets, orally, once daily for up to two weeks.; Other Names: Rozerem™ TAK-375
Placebo Comparator: Placebo QD	Drug: Placebo; Ramelteon placebo-matching tablets, orally, once daily for up to two weeks.

Outcome Measures

Primary Outcome Measures

1. Latency to Persistent Sleep Over a 2-night Average Measured by Polysomnography (Nights 6-7) [Nights 6-7]

   The elapsed time from the beginning of the polysomnography recording to the onset of the first 10 minutes of continuous sleep (ie, total number of epochs before the first 20 consecutive non-wake epochs divided by 2).

Secondary Outcome Measures

1. Latency to Persistent Sleep Over a 2-night Average Measured by Polysomnography (Nights 13-14) [Nights 13-14]

   The elapsed time from the beginning of the polysomnography recording to the onset of the first 10 minutes of continuous sleep (ie, total number of epochs before the first 20 consecutive non-wake epochs divided by 2).

2. Total Sleep Time Over a 2-night Average Measured by Polysomnography (Nights 6-7) [Nights 6-7]

   The sum of all of the minutes of Stages 1, 2, 3, 4, and rapid eye movement (REM) sleep.

3. Total Sleep Time Over a 2-night Average Measured by Polysomnography (Nights 13-14) [Nights 13-14]

   The sum of all of the minutes of Stages 1, 2, 3, 4, and REM sleep.

4. Sleep Efficiency Over a 2-night Average Measured by Polysomnography (0-3 Hours) (Nights 6-7) [Nights 6-7]

   The total sleep time divided by time-in-bed, multiplied by 100.

5. Sleep Efficiency Over a 2-night Average Measured by Polysomnography (0-3 Hours) (Nights 13-14) [Nights 13-14]

   The total sleep time divided by time-in-bed, multiplied by 100.

6. Sleep Efficiency Over a 2-night Average Measured by Polysomnography (0-8 Hours) (Nights 6-7) [Nights 6-7]

   The total sleep time divided by time-in-bed, multiplied by 100.

7. Sleep Efficiency Over a 2-night Average Measured by Polysomnography (0-8 Hours) (Nights 13-14) [Nights 13-14]

   The total sleep time divided by time-in-bed, multiplied by 100.

8. Wake Time After Sleep Onset Over a 2-night Average Measured by Polysomnography (Nights 6-7) [Nights 6-7]

   The number of wake minutes after the onset of persistent sleep prior to the end of recording.

9. Wake Time After Sleep Onset Over a 2-night Average Measured by Polysomnography (Nights 13-14) [Nights 13-14]

   The number of wake minutes after the onset of persistent sleep prior to the end of recording.

10. Number of Awakenings Over a 2-night Average Measured by Polysomnography (Nights 6-7) [Nights 6-7]

    The number of times after onset of persistent sleep that there is a wake entry of at least 2 epochs in duration. Each entry must be separated by stage 2, stage 3/4 non-REM (NREM) sleep, or REM sleep to be counted.

11. Number of Awakenings Over a 2-night Average Measured by Polysomnography (Nights 13-14) [Nights 13-14]

    The number of times after onset of persistent sleep that there is a wake entry of at least 2 epochs in duration. Each entry must be separated by stage 2, stage 3/4 non-REM (NREM) sleep, or REM sleep to be counted.

12. Total Wake Time Over a 2-night Average Measured by Polysomnography (Nights 6-7) [Nights 6-7]

    The sum of all the minutes of Stage Wake from the beginning of the recording to the end of recording.

13. Total Wake Time Over a 2-night Average Measured by Polysomnography (Nights 13-14) [Nights 13-14]

    The sum of all the minutes of Stage Wake from the beginning of the recording to the end of recording.

14. Sleep Time Over a 2-night Average Measured by Polysomnography (Nights 6-7) [Nights 6-7]

    Sleep time was measured as the clock time the subject went to sleep. Units are hours and minutes on a 24-hour clock, expressed in decimal time.

15. Sleep Time Over a 2-night Average Measured by Polysomnography (Nights 13-14) [Nights 13-14]

    Sleep time was measured as the clock time the subject went to sleep. Units are hours and minutes on a 24-hour clock, expressed in decimal time.

16. Wake Time Over a 2-night Average Measured by Polysomnography (Nights 6-7) [Nights 6-7]

    Wake Time was measured as the clock time that the subject got up in the morning. Units are hours and minutes on a 24-hour clock, expressed in decimal time.

17. Wake Time Over a 2-night Average Measured by Polysomnography (Nights 13-14) [Nights 13-14]

    Wake Time was measured as the clock time that the subject got up in the morning. Units are hours and minutes on a 24-hour clock, expressed in decimal time.

18. Total Sleep Time Measured by Actigraphy (Nights 6-7) [Nights 6-7]

    Total sleep time calculated using the total number of epochs (number of movements recorded by actigraphy watch worn by subject) that are less than or equal to 40, measured between the start time and end time during the nocturnal sleep interval, scored as SLEEP by the actigraphy software.

19. Total Sleep Time Measured by Actigraphy (Nights 13-14) [Nights 13-14]

    Total sleep time pertains to the total number of epochs (number of movements recorded by actigraphy watch worn by subject) that are less than or equal to 40, measured between the start time and end time during the nocturnal sleep interval, scored as SLEEP by the actigraphy software.

20. Sleep Efficiency Measured by Actigraphy (Nights 6-7) [Nights 6-7]

    Sleep efficiency pertains to the scored total sleep time (recorded by actigraphy watch worn by subject) of the sleep interval divided by total time in bed minus total invalid time (Sleep/Wake), multiplied by 100.

21. Sleep Efficiency Measured by Actigraphy (Nights 13-14) [Nights 13-14]

    Sleep efficiency pertains to the scored total sleep time (recorded by actigraphy watch worn by subject) of the sleep interval divided by total time in bed minus total invalid time (Sleep/Wake), multiplied by 100.

22. Wake Time During Sleep Interval Measured by Actigraphy (Nights 6-7) [Nights 6-7]

    Wake time during sleep is the total number of epochs (number of movements recorded by actigraphy watch worn by subject) between the start time and the end time of the given sleep interval, scored as WAKE by the software (or manually set as WAKE by the practitioner using the software), multiplied by the Epoch length in minutes.

23. Wake Time During Sleep Interval Measured by Actigraphy (Nights 13-14) [Nights 13-14]

    Wake time during sleep is the total number of epochs (number of movements recorded by actigraphy watch worn by subject) between the start time and the end time of the given sleep interval, scored as WAKE by the software (or manually set as WAKE by the practitioner using the software), multiplied by the Epoch length in minutes.

24. Wake Bouts Measured by Actigraphy (Nights 6-7) [Nights 6-7]

    The number of wake bouts pertains to the total number of continuous blocks (recorded by actigraphy watch worn by subject), with one or more epochs in duration, and with each epoch of each clock scored as WAKE between the start time and the end time of the given interval.

25. Wake Bouts Measured by Actigraphy (Nights 13-14) [Nights 13-14]

    The number of wake bouts pertains to the total number of continuous blocks (recorded by actigraphy watch worn by subject), with one or more epochs in duration, and with each epoch of each clock scored as WAKE between the start time and the end time of the given interval.

26. Sleep Latency Measured by Actigraphy (Nights 6-7) [Nights 6-7]

    The elapsed time from the beginning of the recording to the onset of the first 10 minutes of continuous sleep (recorded by actigraphy watch worn by subject).

27. Sleep Latency Measured by Actigraphy (Nights 13-14) [Nights 13-14]

    The elapsed time from the beginning of the recording to the onset of the first 10 minutes of continuous sleep (recorded by actigraphy watch worn by subject).

28. Sleep Time Measured by Actigraphy (Nights 6-7) [Nights 6-7]

    Clock time subject goes to sleep (recorded by actigraphy watch worn by subject). Units are hours and minutes on a 24-hour clock, expressed in decimal time.

29. Sleep Time Measured by Actigraphy (Nights 13-14) [Nights 13-14]

    Clock time subject goes to sleep (recorded by actigraphy watch worn by subject). Units are hours and minutes on a 24-hour clock, expressed in decimal time.

30. Wake Time Measured by Actigraphy (Nights 6-7) [Nights 6-7]

    Clock time subject wakes up (recorded by actigraphy watch worn by subject). Units are hours and minutes on a 24-hour clock, expressed in decimal time.

31. Wake Time Measured by Actigraphy (Nights 13-14) [Nights 13-14]

    Clock time subject wakes up (recorded by actigraphy watch worn by subject). Units are hours and minutes on a 24-hour clock, expressed in decimal time.

32. Subjective Sleep Latency Measured by a Post-sleep Questionnaire (Nights 6-7) [Nights 6-7]

    Subjective sleep latency was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "How long do you think it took you to fall asleep last night?"

33. Subjective Sleep Latency Measured by a Post-sleep Questionnaire (Nights 13-14) [Nights 13-14]

    Subjective sleep latency was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "How long do you think it took you to fall asleep last night?"

34. Subjective Total Sleep Time Measured by a Post-sleep Questionnaire (Nights 6-7) [Nights 6-7]

    Subjective total sleep time was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "How long (total hours and minutes) do you think you slept last night?"

35. Subjective Total Sleep Time Measured by a Post-sleep Questionnaire (Nights 13-14) [Nights 13-14]

    Subjective total sleep time was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "How long (total hours and minutes) do you think you slept last night?"

36. Subjective Wake Time After Sleep Onset Measured by a Post-sleep Questionnaire (Nights 6-7) [Nights 6-7]

    Subjective wake time after sleep onset was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "Did you wake up during the night? If "yes", what is the total time you think you were awake?"

37. Subjective Wake Time After Sleep Onset Measured by a Post-sleep Questionnaire (Nights 13-14) [Nights 13-14]

    Subjective wake time after sleep onset was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "Did you wake up during the night? If "yes", what is the total time you think you were awake?"

38. Subjective Number of Awakenings Measured by a Post-sleep Questionnaire (Nights 6-7) [Nights 6-7]

    Subjective number of awakenings was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "Did you wake up during the night? If "yes", how many times do you think you woke up?"

39. Subjective Number of Awakenings Measured by a Post-sleep Questionnaire (Nights 13-14) [Nights 13-14]

    Subjective number of awakenings was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "Did you wake up during the night? If "yes", how many times do you think you woke up?"

40. Subjective Sleep Quality Measured by a Post-sleep Questionnaire (Nights 6-7) [Nights 6-7]

    Subjective sleep quality was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "How would you describe the quality of your sleep last night?" Scores were based on the following scale: Extremely Poor=7; Very Poor=6; Poor=5; Fair=4; Good=3; Very Good=2; Excellent=1.

41. Subjective Sleep Quality Measured by a Post-sleep Questionnaire (Nights 13-14) [Nights 13-14]

    Subjective sleep quality was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "How would you describe the quality of your sleep last night?" Scores were based on the following scale: Extremely Poor=7; Very Poor=6; Poor=5; Fair=4; Good=3; Very Good=2; Excellent=1.

42. Subjective Sleep Time Measured by a Post-sleep Questionnaire (Nights 6-7) [Nights 6-7]

    Subjective sleep time was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "What time did you try to go to sleep last night?" Units are hours and minutes on a 24-hour clock, expressed in decimal time.

43. Subjective Sleep Time Measured by a Post-sleep Questionnaire (Nights 13-14) [Nights 13-14]

    Subjective sleep time was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "What time did you try to go to sleep last night?" Units are hours and minutes on a 24-hour clock, expressed in decimal time.

44. Subjective Getting up in the Morning Measured by a Post-sleep Questionnaire (Nights 6-7) [Nights 6-7]

    The score was an average of 2 nights responses. If subjects had a work or school day, the answer to, "How easy was it for you to wake or get up in the morning when on a school or working night?" was based on the following scale: Extremely Difficult =7; Very Difficult =6; Difficult =5; Neither =4; Easy =3; Very Easy =2; Extremely Easy =1.

45. Subjective Getting up in the Morning Measured by a Post-sleep Questionnaire (Nights 13-14) [Nights 13-14]

    The score was an average of 2 nights responses. If subjects had a work or school day, the answer to, "How easy was it for you to wake or get up in the morning when on a school or working night?" was based on the following scale: Extremely Difficult =7; Very Difficult =6; Difficult =5; Neither =4; Easy =3; Very Easy =2; Extremely Easy =1.

46. Subjective Ability to Concentrate in the Morning Measured by a Post-sleep Questionnaire (Nights 6-7) [Nights 6-7]

    Subjective ability to concentrate was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "How would you describe your ability to concentrate this morning?" Scores were based on the following scale: Extremely Poor=7; Very Poor=6; Poor=5; Fair=4; Good=3; Very Good=2; Excellent=1.

47. Subjective Ability to Concentrate in the Morning Measured by a Post-sleep Questionnaire (Nights 13-14) [Nights 13-14]

    Subjective ability to concentrate was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "How would you describe your ability to concentrate this morning?" Scores were based on the following scale: Extremely Poor=7; Very Poor=6; Poor=5; Fair=4; Good=3; Very Good=2; Excellent=1.

48. Subjective Level of Alertness Measured by a Post-sleep Questionnaire (Nights 6-7) [Nights 6-7]

    Subjective level of alertness was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "How would you describe your level of alertness this morning?" Scores were based on the following scale: Extremely Poor=7; Very Poor=6; Poor=5; Fair=4; Good=3; Very Good=2; Excellent=1.

49. Subjective Level of Alertness Measured by a Post-sleep Questionnaire (Nights 13-14) [Nights 13-14]

    Subjective level of alertness was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "How would you describe your level of alertness this morning?" Scores were based on the following scale: Extremely Poor=7; Very Poor=6; Poor=5; Fair=4; Good=3; Very Good=2; Excellent=1.

50. Next Morning Residual Effects Assessments of Psychomotor and Cognitive Function Via Digit Symbol Substitution Test [Day 15]

    The number of correct digit-for-number substitutions on a Digit Symbol Substitution Test in the 90-second period was recorded to assess psychomotor and cognitive function. The score was the average of 2 mornings' tests. Worst Value: 0. Best Value: No Limit.

51. Next Morning Residual Effects Assessments of Psychomotor and Cognitive Function Via Memory Recall Test--Immediate [Day 15]

    After 16 words were read to a subject, a subject was given 2 minutes to write down as many words as he/she remembered. The correct number of words written was scored, and the average of 2 mornings' tests was calculated.

52. Next Morning Residual Effects Assessments of Psychomotor and Cognitive Function Via Memory Recall Test--Delayed [Day 15]

    After 16 words were read to a subject, a subject waited 1 minute and then was given 2 minutes to write down as many words as he/she remembered. The correct number of words written was scored, and the average of 2 mornings' tests was calculated.

53. Visual Analogue Scale for Mood [Day 15]

    Subjects marked visual scales (in millimeters) that represented ranges of emotions (eg, calm to anxious; normal to bloated; energetic to fatigued). Individual subject composite scores were calculated, and the average of 2 tests were analyzed. Worst Value: 0 mm. Best Value: 100 mm. The farther to the left a subject marks, the better their mood; farther to the right, the more distressed the mood. Higher numbers indicate a more distressed mood.

54. Visual Analogue Scale for Feelings [Day 15]

    Subjects marked visual scales (in millimeters) that represented ranges of emotions (eg, calm to anxious; normal to bloated; energetic to fatigued). Individual subject composite scores were calculated, and the average of 2 tests were analyzed. Worst Value:0 mm.. Best Value:100 mm.. The farther to the left a subject marks, the better their mood; farther to the right, the more distressed the mood. Higher numbers indicate a more distressed mood.

55. The Time of Dim Light Melatonin Secretion Onset [Day 15]

    Linear Dim Light Melatonin Secretion Onset is defined as the first time of the evening (on a 24-hour clock) when the melatonin level rises above 3.0 pg/ml with a positive slope. Units are hours and minutes on a 24-hour clock, expressed in decimal time.

56. The Time of Dim Light Melatonin Secretion Offset [Day 15]

    Dim Light Melatonin Secretion Offset is defined as the first time of the morning (on a 24-hour clock) when the melatonin drops to below 3 pg/mL with a negative slope. Units are hours and minutes on a 24-hour clock, expressed in decimal time.

57. The Total Duration of Secretion of Melatonin [Day 15]

    The total duration of time from Dim Light Melatonin Secretion Onset to Dim Light Melatonin Secretion Offset.

58. The Area Under the Concentration-time Curve of Melatonin From 0 to 24 Hours [Day 15]

    Area under the concentration-time curve is a measure of total drug exposure.

59. Average Cmax (Maximum Observed Plasma Concentration) Calculated as the Average of Three Highest Cmax Observations Within the Sampling Period. [Day 15]

    Average Cmax calculated as the average of three highest Cmax observations within the sampling period.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States
2		Tucson	Arizona	United States
3		Hot Springs	Arkansas	United States
4		Little Rock	Arkansas	United States
5		Fountain Valley	California	United States
6		Glendale	California	United States
7		Los Angeles	California	United States
8		San Diego	California	United States
9		Santa Monica	California	United States
10		Tustin	California	United States
11		Colorado Springs	Colorado	United States
12		Hallandale Bch	Florida	United States
13		Naples	Florida	United States
14		Pembroke Pines	Florida	United States
15		South Miami	Florida	United States
16		Spring Hill	Florida	United States
17		St. Petersburg	Florida	United States
18		Winter Park	Florida	United States
19		Atlanta	Georgia	United States
20		Gainesville	Georgia	United States
21		Macon	Georgia	United States
22		Chicago	Illinois	United States
23		Danville	Indiana	United States
24		Overland Park	Kansas	United States
25		Topeka	Kansas	United States
26		Crestview Hills	Kentucky	United States
27		Paducah	Kentucky	United States
28		Chevy Chase	Maryland	United States
29		Newton	Massachusetts	United States
30		Hattiesburg	Mississippi	United States
31		Lincoln	Nebraska	United States
32		Las Vegas	Nevada	United States
33		New York	New York	United States
34		Raleigh	North Carolina	United States
35		Salisbury	North Carolina	United States
36		Cincinnati	Ohio	United States
37		Dublin	Ohio	United States
38		Toledo	Ohio	United States
39		Salem	Oregon	United States
40		Clarks Summit	Pennsylvania	United States
41		Columbia	South Carolina	United States
42		Austin	Texas	United States

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Medical Director Clinical Science, Takeda

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Rozerem Package Insert

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT00593736
• Other Study ID Numbers: 01-04-TL-375-044
• First Posted: Jan 15, 2008
• Last Update Posted: Feb 28, 2012
• Last Verified: Feb 1, 2012

• Keywords provided by Takeda: Delayed sleep phase syndrome; drug therapy
• Additional relevant MeSH terms: Sleep Wake Disorders; Sleep Disorders, Circadian Rhythm

Study Results

Participant Flow

Recruitment Details	Subjects enrolled at 47 sites in the United States from 10 October 2007 to 23 May 2008.
Pre-assignment Detail	Subjects were screened for 14 days, entered a 7-day placebo run-in, and then were randomized to once-daily (QD) treatment. To enter the double-blind randomization period, subjects must have met the eligible inclusion and none of the exclusion criteria and met sleep diagnostic criteria established during screening polysomnography.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Period Title: Screening Period and Placebo Run-in
STARTED	0	0	0	549
COMPLETED	0	0	0	132
NOT COMPLETED	0	0	0	417
Period Title: Screening Period and Placebo Run-in
STARTED	32	33	35	32
COMPLETED	29	31	30	28
NOT COMPLETED	3	2	5	4

Baseline Characteristics

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD	Total
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.	Total of all reporting groups
Overall Participants	32	33	35	32	132
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	29.6 (9.36)	33.7 (12.31)	29.3 (9.40)	33.1 (13.08)	31.4 (11.19)
Sex: Female, Male (Count of Participants)
Female	18 56.3%	17 51.5%	17 48.6%	12 37.5%	64 48.5%
Male	14 43.8%	16 48.5%	18 51.4%	20 62.5%	68 51.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	19 59.4%	19 57.6%	19 54.3%	18 56.3%	75 56.8%
Not Hispanic or Latino	13 40.6%	14 42.4%	16 45.7%	14 43.8%	57 43.2%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 3.1%	0 0%	0 0%	0 0%	1 0.8%
Asian	2 6.3%	0 0%	0 0%	0 0%	2 1.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	1 3.1%	1 0.8%
Black or African American	4 12.5%	3 9.1%	3 8.6%	3 9.4%	13 9.8%
White	24 75%	30 90.9%	32 91.4%	28 87.5%	114 86.4%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	1 3.1%	0 0%	0 0%	0 0%	1 0.8%
Pharmacologic sleep aid needed to sleep (subjects) [Number]
0	31	30	33	32	126
1	0	0	1	0	1
2	0	2	1	0	3
3	1	1	0	0	2
4	0	0	0	0	0
>4	0	0	0	0	0
Time asleep (habitual and desired) (minutes) [Mean (Standard Deviation) ]
Habitual	368.0 (89.27)	406.4 (105.29)	371.6 (95.29)	384.8 (78.88)	382.6 (93.01)
Desired	341.7 (76.46)	347.7 (72.05)	331.3 (75.30)	330.9 (64.43)	337.8 (72.06)
Time to fall asleep (habitual and desired) (minutes) [Mean (Standard Deviation) ]
Habitual	83.0 (78.85)	76.8 (59.89)	90.4 (64.79)	69.8 (58.72)	80.2 (65.66)
Desired	167.5 (53.25)	164.4 (51.43)	165.0 (48.94)	155.0 (55.61)	163.0 (51.89)

Outcome Measures

1. Primary Outcome

Title	Latency to Persistent Sleep Over a 2-night Average Measured by Polysomnography (Nights 6-7)
Description	The elapsed time from the beginning of the polysomnography recording to the onset of the first 10 minutes of continuous sleep (ie, total number of epochs before the first 20 consecutive non-wake epochs divided by 2).
Time Frame	Nights 6-7

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the full analysis set (FAS), which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	31	33	33	30
Least Squares Mean (Standard Error) [minutes]	59.30 (6.684)	39.40 (6.352)	55.94 (6.482)	55.12 (6.871)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the analysis of covariance (ANCOVA) model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.646
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	Least Squares (LS) means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.084
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.929
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

2. Secondary Outcome

Title	Latency to Persistent Sleep Over a 2-night Average Measured by Polysomnography (Nights 13-14)
Description	The elapsed time from the beginning of the polysomnography recording to the onset of the first 10 minutes of continuous sleep (ie, total number of epochs before the first 20 consecutive non-wake epochs divided by 2).
Time Frame	Nights 13-14

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	30	32	32	30
Least Squares Mean (Standard Error) [minutes]	48.36 (6.849)	38.61 (6.611)	45.29 (6.732)	46.64 (6.983)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.854
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS Means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.383
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS Means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.883
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS Means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

3. Secondary Outcome

Title	Total Sleep Time Over a 2-night Average Measured by Polysomnography (Nights 6-7)
Description	The sum of all of the minutes of Stages 1, 2, 3, 4, and rapid eye movement (REM) sleep.
Time Frame	Nights 6-7

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	31	33	33	30
Least Squares Mean (Standard Error) [minutes]	376.41 (8.158)	383.51 (7.876)	378.62 (8.033)	366.23 (8.421)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.365
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS Means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.121
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.269
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

4. Secondary Outcome

Title	Total Sleep Time Over a 2-night Average Measured by Polysomnography (Nights 13-14)
Description	The sum of all of the minutes of Stages 1, 2, 3, 4, and REM sleep.
Time Frame	Nights 13-14

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	30	32	32	30
Least Squares Mean (Standard Error) [minutes]	389.72 (8.866)	378.04 (8.683)	379.17 (8.843)	388.51 (9.064)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.920
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.382
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.439
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

5. Secondary Outcome

Title	Sleep Efficiency Over a 2-night Average Measured by Polysomnography (0-3 Hours) (Nights 6-7)
Description	The total sleep time divided by time-in-bed, multiplied by 100.
Time Frame	Nights 6-7

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	31	33	33	30
Least Squares Mean (Standard Error) [percentage of time asleep]	64.49 (3.385)	71.83 (3.213)	65.70 (3.272)	64.64 (3.460)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.973
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.117
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.816
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

6. Secondary Outcome

Title	Sleep Efficiency Over a 2-night Average Measured by Polysomnography (0-3 Hours) (Nights 13-14)
Description	The total sleep time divided by time-in-bed, multiplied by 100.
Time Frame	Nights 13-14

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	30	32	32	30
Least Squares Mean (Standard Error) [percentage of time asleep]	69.07 (3.244)	75.13 (3.126)	70.19 (3.181)	70.99 (3.286)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.661
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.341
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.853
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

7. Secondary Outcome

Title	Sleep Efficiency Over a 2-night Average Measured by Polysomnography (0-8 Hours) (Nights 6-7)
Description	The total sleep time divided by time-in-bed, multiplied by 100.
Time Frame	Nights 6-7

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	31	33	33	30
Least Squares Mean (Standard Error) [percentage of time asleep]	78.42 (1.701)	79.90 (1.642)	78.89 (1.675)	76.30 (1.756)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.365
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.121
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.268
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

8. Secondary Outcome

Title	Sleep Efficiency Over a 2-night Average Measured by Polysomnography (0-8 Hours) (Nights 13-14)
Description	The total sleep time divided by time-in-bed, multiplied by 100.
Time Frame	Nights 13-14

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	30	32	32	30
Least Squares Mean (Standard Error) [percentage of time asleep]	81.09 (1.706)	79.33 (1.671)	78.92 (1.702)	80.80 (1.745)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.900
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.525
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.418
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

9. Secondary Outcome

Title	Wake Time After Sleep Onset Over a 2-night Average Measured by Polysomnography (Nights 6-7)
Description	The number of wake minutes after the onset of persistent sleep prior to the end of recording.
Time Frame	Nights 6-7

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	31	33	33	30
Least Squares Mean (Standard Error) [minutes]	46.26 (5.880)	62.86 (5.704)	51.06 (5.758)	62.11 (6.035)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.051
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.926
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.166
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

10. Secondary Outcome

Title	Wake Time After Sleep Onset Over a 2-night Average Measured by Polysomnography (Nights 13-14)
Description	The number of wake minutes after the onset of persistent sleep prior to the end of recording.
Time Frame	Nights 13-14

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	30	32	32	30
Least Squares Mean (Standard Error) [minutes]	43.36 (6.124)	63.47 (6.032)	59.77 (6.103)	48.88 (6.240)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.511
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.082
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.188
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

11. Secondary Outcome

Title	Number of Awakenings Over a 2-night Average Measured by Polysomnography (Nights 6-7)
Description	The number of times after onset of persistent sleep that there is a wake entry of at least 2 epochs in duration. Each entry must be separated by stage 2, stage 3/4 non-REM (NREM) sleep, or REM sleep to be counted.
Time Frame	Nights 6-7

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	31	33	33	30
Least Squares Mean (Standard Error) [number of awakenings]	9.22 (0.835)	10.79 (0.795)	10.79 (0.815)	9.67 (0.853)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.691
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.323
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.324
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

12. Secondary Outcome

Title	Number of Awakenings Over a 2-night Average Measured by Polysomnography (Nights 13-14)
Description	The number of times after onset of persistent sleep that there is a wake entry of at least 2 epochs in duration. Each entry must be separated by stage 2, stage 3/4 non-REM (NREM) sleep, or REM sleep to be counted.
Time Frame	Nights 13-14

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	30	32	32	30
Least Squares Mean (Standard Error) [number of awakenings]	8.08 (0.806)	9.33 (0.783)	9.87 (0.800)	9.51 (0.822)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.197
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.871
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.737
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

13. Secondary Outcome

Title	Total Wake Time Over a 2-night Average Measured by Polysomnography (Nights 6-7)
Description	The sum of all the minutes of Stage Wake from the beginning of the recording to the end of recording.
Time Frame	Nights 6-7

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	31	33	33	30
Least Squares Mean (Standard Error) [minutes]	63.92 (6.096)	50.67 (5.785)	61.67 (5.892)	63.63 (6.230)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.972
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.117
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.811
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

14. Secondary Outcome

Title	Total Wake Time Over a 2-night Average Measured by Polysomnography (Nights 13-14)
Description	The sum of all the minutes of Stage Wake from the beginning of the recording to the end of recording.
Time Frame	Nights 13-14

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	30	32	32	30
Least Squares Mean (Standard Error) [minutes]	55.69 (5.841)	44.68 (5.629)	53.64 (5.728)	52.19 (5.918)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.659
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.337
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.853
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

15. Secondary Outcome

Title	Sleep Time Over a 2-night Average Measured by Polysomnography (Nights 6-7)
Description	Sleep time was measured as the clock time the subject went to sleep. Units are hours and minutes on a 24-hour clock, expressed in decimal time.
Time Frame	Nights 6-7

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	31	33	33	30
Least Squares Mean (Standard Error) [hours on a 24-hour clock]	22.40 (0.016)	22.36 (0.016)	22.35 (0.016)	22.35 (0.033)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.206
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.495
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.800
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

16. Secondary Outcome

Title	Sleep Time Over a 2-night Average Measured by Polysomnography (Nights 13-14)
Description	Sleep time was measured as the clock time the subject went to sleep. Units are hours and minutes on a 24-hour clock, expressed in decimal time.
Time Frame	Nights 13-14

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	30	32	32	30
Least Squares Mean (Standard Error) [hours on a 24-hour clock]	22.36 (0.016)	22.36 (0.016)	22.36 (0.016)	22.33 (0.016)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.194
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.134
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.130
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

17. Secondary Outcome

Title	Wake Time Over a 2-night Average Measured by Polysomnography (Nights 6-7)
Description	Wake Time was measured as the clock time that the subject got up in the morning. Units are hours and minutes on a 24-hour clock, expressed in decimal time.
Time Frame	Nights 6-7

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	31	33	33	30
Least Squares Mean (Standard Error) [hours on a 24-hour clock]	06.35 (0.033)	06.31 (0.033)	06.30 (0.033)	06.26 (0.033)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.063
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.156
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.521
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

18. Secondary Outcome

Title	Wake Time Over a 2-night Average Measured by Polysomnography (Nights 13-14)
Description	Wake Time was measured as the clock time that the subject got up in the morning. Units are hours and minutes on a 24-hour clock, expressed in decimal time.
Time Frame	Nights 13-14

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	30	32	32	30
Least Squares Mean (Standard Error) [hours on a 24-hour clock]	06.31 (0.066)	06.21 (0.066)	06.40 (0.066)	06.26 (0.083)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.675
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.566
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.205
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

19. Secondary Outcome

Title	Total Sleep Time Measured by Actigraphy (Nights 6-7)
Description	Total sleep time calculated using the total number of epochs (number of movements recorded by actigraphy watch worn by subject) that are less than or equal to 40, measured between the start time and end time during the nocturnal sleep interval, scored as SLEEP by the actigraphy software.
Time Frame	Nights 6-7

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	26	28	28	29
Least Squares Mean (Standard Error) [minutes]	374.37 (8.741)	393.37 (8.632)	370.83 (8.352)	369.05 (8.457)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.643
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.032
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.875
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

20. Secondary Outcome

Title	Total Sleep Time Measured by Actigraphy (Nights 13-14)
Description	Total sleep time pertains to the total number of epochs (number of movements recorded by actigraphy watch worn by subject) that are less than or equal to 40, measured between the start time and end time during the nocturnal sleep interval, scored as SLEEP by the actigraphy software.
Time Frame	Nights 13-14

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	26	27	30	27
Least Squares Mean (Standard Error) [minutes]	391.61 (8.661)	390.76 (8.982)	370.80 (8.228)	378.91 (8.845)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.286
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.318
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.483
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

21. Secondary Outcome

Title	Sleep Efficiency Measured by Actigraphy (Nights 6-7)
Description	Sleep efficiency pertains to the scored total sleep time (recorded by actigraphy watch worn by subject) of the sleep interval divided by total time in bed minus total invalid time (Sleep/Wake), multiplied by 100.
Time Frame	Nights 6-7

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	26	28	28	29
Least Squares Mean (Standard Error) [percentage of time asleep]	85.79 (1.117)	83.46 (1.086)	81.38 (1.081)	82.72 (1.089)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.040
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.610
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.368
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

22. Secondary Outcome

Title	Sleep Efficiency Measured by Actigraphy (Nights 13-14)
Description	Sleep efficiency pertains to the scored total sleep time (recorded by actigraphy watch worn by subject) of the sleep interval divided by total time in bed minus total invalid time (Sleep/Wake), multiplied by 100.
Time Frame	Nights 13-14

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	26	27	30	27
Least Squares Mean (Standard Error) [percentage of time asleep]	84.98 (1.349)	82.91 (1.381)	81.31 (1.300)	83.24 (1.388)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.352
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.860
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.297
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

23. Secondary Outcome

Title	Wake Time During Sleep Interval Measured by Actigraphy (Nights 6-7)
Description	Wake time during sleep is the total number of epochs (number of movements recorded by actigraphy watch worn by subject) between the start time and the end time of the given sleep interval, scored as WAKE by the software (or manually set as WAKE by the practitioner using the software), multiplied by the Epoch length in minutes.
Time Frame	Nights 6-7

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	26	28	28	29
Least Squares Mean (Standard Error) [minutes]	41.81 (4.404)	51.98 (4.298)	54.70 (4.211)	53.14 (4.223)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.053
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.837
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.783
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

24. Secondary Outcome

Title	Wake Time During Sleep Interval Measured by Actigraphy (Nights 13-14)
Description	Wake time during sleep is the total number of epochs (number of movements recorded by actigraphy watch worn by subject) between the start time and the end time of the given sleep interval, scored as WAKE by the software (or manually set as WAKE by the practitioner using the software), multiplied by the Epoch length in minutes.
Time Frame	Nights 13-14

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	26	27	30	27
Least Squares Mean (Standard Error) [minutes]	48.11 (4.074)	54.72 (4.185)	52.36 (3.874)	51.32 (4.140)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.566
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.543
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.847
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

25. Secondary Outcome

Title	Wake Bouts Measured by Actigraphy (Nights 6-7)
Description	The number of wake bouts pertains to the total number of continuous blocks (recorded by actigraphy watch worn by subject), with one or more epochs in duration, and with each epoch of each clock scored as WAKE between the start time and the end time of the given interval.
Time Frame	Nights 6-7

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	26	28	28	29
Least Squares Mean (Standard Error) [wake bouts]	20.98 (1.518)	22.91 (1.476)	23.32 (1.457)	22.82 (1.442)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.356
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.964
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.799
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

26. Secondary Outcome

Title	Wake Bouts Measured by Actigraphy (Nights 13-14)
Description	The number of wake bouts pertains to the total number of continuous blocks (recorded by actigraphy watch worn by subject), with one or more epochs in duration, and with each epoch of each clock scored as WAKE between the start time and the end time of the given interval.
Time Frame	Nights 13-14

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	26	27	30	27
Least Squares Mean (Standard Error) [wake bouts]	23.42 (1.201)	24.21 (1.230)	23.52 (1.146)	22.78 (1.206)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.698
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.385
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.641
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

27. Secondary Outcome

Title	Sleep Latency Measured by Actigraphy (Nights 6-7)
Description	The elapsed time from the beginning of the recording to the onset of the first 10 minutes of continuous sleep (recorded by actigraphy watch worn by subject).
Time Frame	Nights 6-7

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	26	28	28	29
Least Squares Mean (Standard Error) [minutes]	12.53 (3.292)	18.05 (3.280)	25.00 (3.156)	12.42 (3.129)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.979
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.194
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

28. Secondary Outcome

Title	Sleep Latency Measured by Actigraphy (Nights 13-14)
Description	The elapsed time from the beginning of the recording to the onset of the first 10 minutes of continuous sleep (recorded by actigraphy watch worn by subject).
Time Frame	Nights 13-14

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	26	27	30	27
Least Squares Mean (Standard Error) [minutes]	12.10 (6.145)	16.40 (6.460)	25.43 (5.859)	12.36 (6.169)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.975
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.639
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.109
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

29. Secondary Outcome

Title	Sleep Time Measured by Actigraphy (Nights 6-7)
Description	Clock time subject goes to sleep (recorded by actigraphy watch worn by subject). Units are hours and minutes on a 24-hour clock, expressed in decimal time.
Time Frame	Nights 6-7

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	26	28	28	29
Least Squares Mean (Standard Error) [hours on a 24-hour clock]	23.28 (0.150)	22.75 (0.150)	23.11 (0.150)	23.31 (0.150)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.823
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.296
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

30. Secondary Outcome

Title	Sleep Time Measured by Actigraphy (Nights 13-14)
Description	Clock time subject goes to sleep (recorded by actigraphy watch worn by subject). Units are hours and minutes on a 24-hour clock, expressed in decimal time.
Time Frame	Nights 13-14

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	26	27	30	27
Least Squares Mean (Standard Error) [hours on a 24-hour clock]	22.83 (0.150)	22.71 (0.166)	23.11 (0.150)	23.18 (0.150)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.092
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.025
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.732
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

31. Secondary Outcome

Title	Wake Time Measured by Actigraphy (Nights 6-7)
Description	Clock time subject wakes up (recorded by actigraphy watch worn by subject). Units are hours and minutes on a 24-hour clock, expressed in decimal time.
Time Frame	Nights 6-7

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	26	28	28	29
Least Squares Mean (Standard Error) [hours on a 24-hour clock]	06.20 (0.116)	06.18 (0.116)	06.23 (0.116)	06.36 (0.116)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.298
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.276
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.430
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

32. Secondary Outcome

Title	Wake Time Measured by Actigraphy (Nights 13-14)
Description	Clock time subject wakes up (recorded by actigraphy watch worn by subject). Units are hours and minutes on a 24-hour clock, expressed in decimal time.
Time Frame	Nights 13-14

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	26	27	30	27
Least Squares Mean (Standard Error) [hours on a 24-hour clock]	06.13 (0.133)	06.08 (0.133)	06.16 (0.133)	06.30 (0.133)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.349
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.203
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.444
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

33. Secondary Outcome

Title	Subjective Sleep Latency Measured by a Post-sleep Questionnaire (Nights 6-7)
Description	Subjective sleep latency was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "How long do you think it took you to fall asleep last night?"
Time Frame	Nights 6-7

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	31	33	34	30
Least Squares Mean (Standard Error) [minutes]	103.55 (8.301)	84.46 (8.087)	92.79 (7.930)	97.28 (8.491)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.581
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.257
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.688
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

34. Secondary Outcome

Title	Subjective Sleep Latency Measured by a Post-sleep Questionnaire (Nights 13-14)
Description	Subjective sleep latency was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "How long do you think it took you to fall asleep last night?"
Time Frame	Nights 13-14

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	28	29	32	30
Least Squares Mean (Standard Error) [minutes]	80.57 (7.406)	69.40 (7.423)	77.29 (7.178)	74.75 (7.407)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.561
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.595
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.795
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

35. Secondary Outcome

Title	Subjective Total Sleep Time Measured by a Post-sleep Questionnaire (Nights 6-7)
Description	Subjective total sleep time was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "How long (total hours and minutes) do you think you slept last night?"
Time Frame	Nights 6-7

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	31	33	34	30
Least Squares Mean (Standard Error) [minutes]	348.10 (10.302)	370.14 (10.067)	360.57 (9.883)	341.76 (10.571)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.655
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.177
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.044
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

36. Secondary Outcome

Title	Subjective Total Sleep Time Measured by a Post-sleep Questionnaire (Nights 13-14)
Description	Subjective total sleep time was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "How long (total hours and minutes) do you think you slept last night?"
Time Frame	Nights 13-14

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	28	29	32	30
Least Squares Mean (Standard Error) [minutes]	379.20 (10.490)	375.73 (10.532)	365.14 (10.229)	368.99 (10.513)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.475
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.635
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.782
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

37. Secondary Outcome

Title	Subjective Wake Time After Sleep Onset Measured by a Post-sleep Questionnaire (Nights 6-7)
Description	Subjective wake time after sleep onset was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "Did you wake up during the night? If "yes", what is the total time you think you were awake?"
Time Frame	Nights 6-7

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	31	33	34	30
Least Squares Mean (Standard Error) [minutes]	35.15 (7.084)	52.52 (6.671)	34.41 (6.659)	47.84 (7.100)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.192
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.618
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.152
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

38. Secondary Outcome

Title	Subjective Wake Time After Sleep Onset Measured by a Post-sleep Questionnaire (Nights 13-14)
Description	Subjective wake time after sleep onset was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "Did you wake up during the night? If "yes", what is the total time you think you were awake?"
Time Frame	Nights 13-14

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	28	29	32	30
Least Squares Mean (Standard Error) [minutes]	23.49 (5.882)	45.54 (5.877)	28.66 (5.669)	30.52 (5.794)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.379
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.057
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.808
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

39. Secondary Outcome

Title	Subjective Number of Awakenings Measured by a Post-sleep Questionnaire (Nights 6-7)
Description	Subjective number of awakenings was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "Did you wake up during the night? If "yes", how many times do you think you woke up?"
Time Frame	Nights 6-7

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	25	27	21	22
Least Squares Mean (Standard Error) [number of awakenings]	2.68 (0.364)	3.72 (0.382)	2.92 (0.385)	3.23 (0.383)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.284
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.344
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.558
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

40. Secondary Outcome

Title	Subjective Number of Awakenings Measured by a Post-sleep Questionnaire (Nights 13-14)
Description	Subjective number of awakenings was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "Did you wake up during the night? If "yes", how many times do you think you woke up?"
Time Frame	Nights 13-14

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	19	22	21	22
Least Squares Mean (Standard Error) [number of awakenings]	2.94 (0.456)	3.72 (0.427)	3.33 (0.443)	3.04 (0.423)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.867
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.244
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.620
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

41. Secondary Outcome

Title	Subjective Sleep Quality Measured by a Post-sleep Questionnaire (Nights 6-7)
Description	Subjective sleep quality was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "How would you describe the quality of your sleep last night?" Scores were based on the following scale: Extremely Poor=7; Very Poor=6; Poor=5; Fair=4; Good=3; Very Good=2; Excellent=1.
Time Frame	Nights 6-7

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	31	33	34	30
Least Squares Mean (Standard Error) [scores on a scale]	4.45 (0.169)	4.61 (0.166)	4.33 (0.162)	4.74 (0.173)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.206
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.559
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.074
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

42. Secondary Outcome

Title	Subjective Sleep Quality Measured by a Post-sleep Questionnaire (Nights 13-14)
Description	Subjective sleep quality was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "How would you describe the quality of your sleep last night?" Scores were based on the following scale: Extremely Poor=7; Very Poor=6; Poor=5; Fair=4; Good=3; Very Good=2; Excellent=1.
Time Frame	Nights 13-14

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	28	29	32	30
Least Squares Mean (Standard Error) [scores on a scale]	4.27 (0.184)	4.35 (0.185)	4.03 (0.179)	4.20 (0.184)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.796
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.546
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.479
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

43. Secondary Outcome

Title	Subjective Sleep Time Measured by a Post-sleep Questionnaire (Nights 6-7)
Description	Subjective sleep time was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "What time did you try to go to sleep last night?" Units are hours and minutes on a 24-hour clock, expressed in decimal time.
Time Frame	Nights 6-7

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	31	33	34	30
Least Squares Mean (Standard Error) [hours on a 24-hour clock]	10.36 (0.066)	10.41 (0.066)	10.40 (0.066)	10.40 (0.066)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.766
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.912
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.952
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

44. Secondary Outcome

Title	Subjective Sleep Time Measured by a Post-sleep Questionnaire (Nights 13-14)
Description	Subjective sleep time was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "What time did you try to go to sleep last night?" Units are hours and minutes on a 24-hour clock, expressed in decimal time.
Time Frame	Nights 13-14

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	28	29	32	30
Least Squares Mean (Standard Error) [hours on a 24-hour clock]	10.36 (0.066)	10.30 (0.066)	10.36 (0.066)	10.40 (0.066)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.722
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.262
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.717
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

45. Secondary Outcome

Title	Subjective Getting up in the Morning Measured by a Post-sleep Questionnaire (Nights 6-7)
Description	The score was an average of 2 nights responses. If subjects had a work or school day, the answer to, "How easy was it for you to wake or get up in the morning when on a school or working night?" was based on the following scale: Extremely Difficult =7; Very Difficult =6; Difficult =5; Neither =4; Easy =3; Very Easy =2; Extremely Easy =1.
Time Frame	Nights 6-7

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	25	29	31	24
Least Squares Mean (Standard Error) [scores on a scale]	4.68 (0.224)	4.76 (0.202)	4.67 (0.178)	4.88 (0.203)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.498
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.664
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.428
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

46. Secondary Outcome

Title	Subjective Getting up in the Morning Measured by a Post-sleep Questionnaire (Nights 13-14)
Description	The score was an average of 2 nights responses. If subjects had a work or school day, the answer to, "How easy was it for you to wake or get up in the morning when on a school or working night?" was based on the following scale: Extremely Difficult =7; Very Difficult =6; Difficult =5; Neither =4; Easy =3; Very Easy =2; Extremely Easy =1.
Time Frame	Nights 13-14

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	24	23	26	25
Least Squares Mean (Standard Error) [scores on a scale]	4.46 (0.219)	4.66 (0.217)	4.30 (0.191)	4.28 (0.198)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.519
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.179
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.935
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

47. Secondary Outcome

Title	Subjective Ability to Concentrate in the Morning Measured by a Post-sleep Questionnaire (Nights 6-7)
Description	Subjective ability to concentrate was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "How would you describe your ability to concentrate this morning?" Scores were based on the following scale: Extremely Poor=7; Very Poor=6; Poor=5; Fair=4; Good=3; Very Good=2; Excellent=1.
Time Frame	Nights 6-7

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	31	33	34	30
Least Squares Mean (Standard Error) [scores on a scale]	4.31 (0.155)	4.30 (0.151)	4.40 (0.148)	4.48 (0.159)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.425
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.406
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.720
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

48. Secondary Outcome

Title	Subjective Ability to Concentrate in the Morning Measured by a Post-sleep Questionnaire (Nights 13-14)
Description	Subjective ability to concentrate was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "How would you describe your ability to concentrate this morning?" Scores were based on the following scale: Extremely Poor=7; Very Poor=6; Poor=5; Fair=4; Good=3; Very Good=2; Excellent=1.
Time Frame	Nights 13-14

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	28	29	32	30
Least Squares Mean (Standard Error) [scores on a scale]	3.77 (0.164)	4.17 (0.164)	4.01 (0.159)	4.01 (0.164)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.294
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.474
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.999
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

49. Secondary Outcome

Title	Subjective Level of Alertness Measured by a Post-sleep Questionnaire (Nights 6-7)
Description	Subjective level of alertness was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "How would you describe your level of alertness this morning?" Scores were based on the following scale: Extremely Poor=7; Very Poor=6; Poor=5; Fair=4; Good=3; Very Good=2; Excellent=1.
Time Frame	Nights 6-7

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	31	31	34	30
Least Squares Mean (Standard Error) [scores on a scale]	4.43 (0.158)	4.32 (0.155)	4.33 (0.152)	4.53 (0.163)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.655
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.331
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.362
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

50. Secondary Outcome

Title	Subjective Level of Alertness Measured by a Post-sleep Questionnaire (Nights 13-14)
Description	Subjective level of alertness was an average of 2 nights responses and measured by post-sleep questionnaire in response to the question, "How would you describe your level of alertness this morning?" Scores were based on the following scale: Extremely Poor=7; Very Poor=6; Poor=5; Fair=4; Good=3; Very Good=2; Excellent=1.
Time Frame	Nights 13-14

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	28	29	32	30
Least Squares Mean (Standard Error) [scores on a scale]	4.02 (0.181)	4.32 (0.181)	3.99 (0.176)	4.12 (0.182)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.684
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.399
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.611
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

51. Secondary Outcome

Title	Next Morning Residual Effects Assessments of Psychomotor and Cognitive Function Via Digit Symbol Substitution Test
Description	The number of correct digit-for-number substitutions on a Digit Symbol Substitution Test in the 90-second period was recorded to assess psychomotor and cognitive function. The score was the average of 2 mornings' tests. Worst Value: 0. Best Value: No Limit.
Time Frame	Day 15

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	30	31	32	29
Least Squares Mean (Standard Error) [Scores on a scale]	44.1 (1.77)	42.4 (1.74)	39.9 (1.74)	40.6 (1.83)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.157
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.463
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.774
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

52. Secondary Outcome

Title	Next Morning Residual Effects Assessments of Psychomotor and Cognitive Function Via Memory Recall Test--Immediate
Description	After 16 words were read to a subject, a subject was given 2 minutes to write down as many words as he/she remembered. The correct number of words written was scored, and the average of 2 mornings' tests was calculated.
Time Frame	Day 15

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	30	30	32	29
Least Squares Mean (Standard Error) [score]	8.1 (0.39)	7.7 (0.40)	8.6 (0.39)	8.6 (0.41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.413
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.093
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.982
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

53. Secondary Outcome

Title	Next Morning Residual Effects Assessments of Psychomotor and Cognitive Function Via Memory Recall Test--Delayed
Description	After 16 words were read to a subject, a subject waited 1 minute and then was given 2 minutes to write down as many words as he/she remembered. The correct number of words written was scored, and the average of 2 mornings' tests was calculated.
Time Frame	Day 15

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	30	30	32	29
Least Squares Mean (Standard Error) [score]	6.5 (0.51)	5.9 (0.51)	6.7 (0.50)	7.1 (0.52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.441
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.082
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.549
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

54. Secondary Outcome

Title	Visual Analogue Scale for Mood
Description	Subjects marked visual scales (in millimeters) that represented ranges of emotions (eg, calm to anxious; normal to bloated; energetic to fatigued). Individual subject composite scores were calculated, and the average of 2 tests were analyzed. Worst Value: 0 mm. Best Value: 100 mm. The farther to the left a subject marks, the better their mood; farther to the right, the more distressed the mood. Higher numbers indicate a more distressed mood.
Time Frame	Day 15

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	30	31	32	29
Least Squares Mean (Standard Error) [Units on a scale]	34.2 (3.20)	33.4 (3.15)	34.3 (3.17)	33.4 (3.31)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.860
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.997
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.834
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

55. Secondary Outcome

Title	Visual Analogue Scale for Feelings
Description	Subjects marked visual scales (in millimeters) that represented ranges of emotions (eg, calm to anxious; normal to bloated; energetic to fatigued). Individual subject composite scores were calculated, and the average of 2 tests were analyzed. Worst Value:0 mm.. Best Value:100 mm.. The farther to the left a subject marks, the better their mood; farther to the right, the more distressed the mood. Higher numbers indicate a more distressed mood.
Time Frame	Day 15

Outcome Measure Data

Analysis Population Description

Analysis was conducted on the FAS, which consisted of all randomized subjects who had at least a baseline assessment and 1 post-baseline assessment.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	30	31	32	30
Least Squares Mean (Standard Error) [Units on a scale]	37.3 (1.52)	34.8 (1.50)	36.8 (1.50)	36.9 (1.57)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.837
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.321
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.978
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

56. Secondary Outcome

Title	The Time of Dim Light Melatonin Secretion Onset
Description	Linear Dim Light Melatonin Secretion Onset is defined as the first time of the evening (on a 24-hour clock) when the melatonin level rises above 3.0 pg/ml with a positive slope. Units are hours and minutes on a 24-hour clock, expressed in decimal time.
Time Frame	Day 15

Outcome Measure Data

Analysis Population Description

The melatonin set included all subjects who had saliva samples collected under dim light conditions for melatonin measurement.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	25	29	31	25
Least Squares Mean (Standard Error) [hours on a 24-hour clock]	21.40 (0.183)	21.30 (0.166)	20.93 (0.166)	21.21 (0.200)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.513
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.751
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.242
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

57. Secondary Outcome

Title	The Time of Dim Light Melatonin Secretion Offset
Description	Dim Light Melatonin Secretion Offset is defined as the first time of the morning (on a 24-hour clock) when the melatonin drops to below 3 pg/mL with a negative slope. Units are hours and minutes on a 24-hour clock, expressed in decimal time.
Time Frame	Day 15

Outcome Measure Data

Analysis Population Description

The melatonin set included all subjects who had saliva samples collected under dim light conditions for melatonin measurement.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	25	29	31	25
Least Squares Mean (Standard Error) [hours on a 24-hour clock]	11.21 (0.250)	10.73 (0.250)	10.96 (0.250)	10.85 (0.283)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.307
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.765
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.727
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

58. Secondary Outcome

Title	The Total Duration of Secretion of Melatonin
Description	The total duration of time from Dim Light Melatonin Secretion Onset to Dim Light Melatonin Secretion Offset.
Time Frame	Day 15

Outcome Measure Data

Analysis Population Description

The melatonin set included all subjects who had saliva samples collected under dim light conditions for melatonin measurement.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	25	29	31	25
Least Squares Mean (Standard Error) [minutes]	1021.8 (34.13)	1003.1 (31.98)	980.2 (31.43)	1027.9 (36.39)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.902
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.590
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.290
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

59. Secondary Outcome

Title	The Area Under the Concentration-time Curve of Melatonin From 0 to 24 Hours
Description	Area under the concentration-time curve is a measure of total drug exposure.
Time Frame	Day 15

Outcome Measure Data

Analysis Population Description

The melatonin set included all subjects who had saliva samples collected under dim light conditions for melatonin measurement.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	25	29	31	25
Least Squares Mean (Standard Error) [μg/dL/hour]	608.5 (40.13)	563.3 (38.08)	528.3 (37.35)	631.5 (42.77)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.685
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.214
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.055
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

60. Secondary Outcome

Title	Average Cmax (Maximum Observed Plasma Concentration) Calculated as the Average of Three Highest Cmax Observations Within the Sampling Period.
Description	Average Cmax calculated as the average of three highest Cmax observations within the sampling period.
Time Frame	Day 15

Outcome Measure Data

Analysis Population Description

The melatonin set included all subjects who had saliva samples collected under dim light conditions for melatonin measurement.

Arm/Group Title	Ramelteon 1 mg QD	Ramelteon 4 mg QD	Ramelteon 8 mg QD	Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Measure Participants	25	29	31	25
Least Squares Mean (Standard Error) [μg/dL]	75.3 (5.12)	69.3 (4.84)	65.2 (4.77)	79.2 (5.46)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 1 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.589
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 4 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.156
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg QD, Placebo QD
	Comments	The comparison between the 2 treatment groups was made using the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.041
	Comments	Statistical significance was determined at the 0.05 level.
	Method	ANCOVA
	Comments	LS means were estimated using an ANCOVA model with treatment and pooled center as class effects and baseline value as a covariate.

Adverse Events

Adverse Event Reporting Description	There were no Serious Adverse Events
Arm/Group Title	Ramelteon 1 mg QD		Ramelteon 4 mg QD		Ramelteon 8 mg QD		Placebo QD
Arm/Group Description	Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.		Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.		Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.		Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
All Cause Mortality
	Ramelteon 1 mg QD		Ramelteon 4 mg QD		Ramelteon 8 mg QD		Placebo QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Ramelteon 1 mg QD		Ramelteon 4 mg QD		Ramelteon 8 mg QD		Placebo QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/32 (0%)		0/33 (0%)		0/35 (0%)		0/32 (0%)
Other (Not Including Serious) Adverse Events
	Ramelteon 1 mg QD		Ramelteon 4 mg QD		Ramelteon 8 mg QD		Placebo QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/32 (21.9%)		5/33 (15.2%)		6/35 (17.1%)		4/32 (12.5%)
Investigations
Blood Creatine Phosphokinase Increased	1/32 (3.1%)		0/33 (0%)		2/35 (5.7%)		1/32 (3.1%)
Musculoskeletal and connective tissue disorders
Pain in Extremity	0/32 (0%)		2/33 (6.1%)		0/35 (0%)		0/32 (0%)
Nervous system disorders
Headache	4/32 (12.5%)		1/33 (3%)		3/35 (8.6%)		1/32 (3.1%)
Somnolence	2/32 (6.3%)		2/33 (6.1%)		1/35 (2.9%)		2/32 (6.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The sponsor can review results communications prior to public release; such communications can be embargoed for a period up to 150 days to permit actions necessary to preserve sponsor's intellectual property. Sponsor can request changes to the results communication only for the purpose of removing non study related information that is proprietary and confidential to sponsor. Sponsor can require delay of a results communication until the study has been completed at all participating sites.