Trial Outcomes & Findings for Efficacy of Ramelteon on Speeding Up Sleep in Subjects With Delayed Sleep Phase Syndrome (NCT NCT00593736)

NCT ID: NCT00593736

Last Updated: 2012-02-28

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 132 participants
• Primary outcome timeframe: Nights 6-7
• Results posted on: 2012-02-28

Participant Flow

Subjects enrolled at 47 sites in the United States from 10 October 2007 to 23 May 2008.

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.

Participant milestones

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

Reasons for withdrawal

Measure	Ramelteon 1 mg QD Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Screening Period and Placebo Run-in Adverse Event	0	0	0	3
Screening Period and Placebo Run-in Lost to Follow-up	0	0	0	9
Screening Period and Placebo Run-in Withdrawal by Subject	0	0	0	43
Screening Period and Placebo Run-in Study Termination	0	0	0	15
Screening Period and Placebo Run-in Did Not Meet Criteria	0	0	0	322
Screening Period and Placebo Run-in Various	0	0	0	25
Treatment Period and Placebo Run-out Lost to Follow-up	2	1	2	0
Treatment Period and Placebo Run-out Protocol Violation	0	0	1	1
Treatment Period and Placebo Run-out Withdrawal by Subject	0	0	1	3
Treatment Period and Placebo Run-out Various	1	1	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Ramelteon 1 mg QD n=32 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=33 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=35 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=32 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.	Total n=132 Participants Total of all reporting groups
Age Continuous	29.6 years STANDARD_DEVIATION 9.36 • n=5 Participants	33.7 years STANDARD_DEVIATION 12.31 • n=7 Participants	29.3 years STANDARD_DEVIATION 9.40 • n=5 Participants	33.1 years STANDARD_DEVIATION 13.08 • n=4 Participants	31.4 years STANDARD_DEVIATION 11.19 • n=21 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	17 Participants n=7 Participants	17 Participants n=5 Participants	12 Participants n=4 Participants	64 Participants n=21 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	16 Participants n=7 Participants	18 Participants n=5 Participants	20 Participants n=4 Participants	68 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	19 Participants n=5 Participants	19 Participants n=7 Participants	19 Participants n=5 Participants	18 Participants n=4 Participants	75 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=5 Participants	14 Participants n=7 Participants	16 Participants n=5 Participants	14 Participants n=4 Participants	57 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	13 Participants n=21 Participants
Race (NIH/OMB) White	24 Participants n=5 Participants	30 Participants n=7 Participants	32 Participants n=5 Participants	28 Participants n=4 Participants	114 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Pharmacologic sleep aid needed to sleep 0	31 subjects n=5 Participants	30 subjects n=7 Participants	33 subjects n=5 Participants	32 subjects n=4 Participants	126 subjects n=21 Participants
Pharmacologic sleep aid needed to sleep 1	0 subjects n=5 Participants	0 subjects n=7 Participants	1 subjects n=5 Participants	0 subjects n=4 Participants	1 subjects n=21 Participants
Pharmacologic sleep aid needed to sleep 2	0 subjects n=5 Participants	2 subjects n=7 Participants	1 subjects n=5 Participants	0 subjects n=4 Participants	3 subjects n=21 Participants
Pharmacologic sleep aid needed to sleep 3	1 subjects n=5 Participants	1 subjects n=7 Participants	0 subjects n=5 Participants	0 subjects n=4 Participants	2 subjects n=21 Participants
Pharmacologic sleep aid needed to sleep 4	0 subjects n=5 Participants	0 subjects n=7 Participants	0 subjects n=5 Participants	0 subjects n=4 Participants	0 subjects n=21 Participants
Pharmacologic sleep aid needed to sleep >4	0 subjects n=5 Participants	0 subjects n=7 Participants	0 subjects n=5 Participants	0 subjects n=4 Participants	0 subjects n=21 Participants
Time asleep (habitual and desired) Habitual	368.0 minutes STANDARD_DEVIATION 89.27 • n=5 Participants	406.4 minutes STANDARD_DEVIATION 105.29 • n=7 Participants	371.6 minutes STANDARD_DEVIATION 95.29 • n=5 Participants	384.8 minutes STANDARD_DEVIATION 78.88 • n=4 Participants	382.6 minutes STANDARD_DEVIATION 93.01 • n=21 Participants
Time asleep (habitual and desired) Desired	341.7 minutes STANDARD_DEVIATION 76.46 • n=5 Participants	347.7 minutes STANDARD_DEVIATION 72.05 • n=7 Participants	331.3 minutes STANDARD_DEVIATION 75.30 • n=5 Participants	330.9 minutes STANDARD_DEVIATION 64.43 • n=4 Participants	337.8 minutes STANDARD_DEVIATION 72.06 • n=21 Participants
Time to fall asleep (habitual and desired) Habitual	83.0 minutes STANDARD_DEVIATION 78.85 • n=5 Participants	76.8 minutes STANDARD_DEVIATION 59.89 • n=7 Participants	90.4 minutes STANDARD_DEVIATION 64.79 • n=5 Participants	69.8 minutes STANDARD_DEVIATION 58.72 • n=4 Participants	80.2 minutes STANDARD_DEVIATION 65.66 • n=21 Participants
Time to fall asleep (habitual and desired) Desired	167.5 minutes STANDARD_DEVIATION 53.25 • n=5 Participants	164.4 minutes STANDARD_DEVIATION 51.43 • n=7 Participants	165.0 minutes STANDARD_DEVIATION 48.94 • n=5 Participants	155.0 minutes STANDARD_DEVIATION 55.61 • n=4 Participants	163.0 minutes STANDARD_DEVIATION 51.89 • n=21 Participants

PRIMARY outcome

Timeframe: Nights 6-7

Population: 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.

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).

Outcome measures

Measure	Ramelteon 1 mg QD n=31 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=33 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=33 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Latency to Persistent Sleep Over a 2-night Average Measured by Polysomnography (Nights 6-7)	59.30 minutes Standard Error 6.684	39.40 minutes Standard Error 6.352	55.94 minutes Standard Error 6.482	55.12 minutes Standard Error 6.871

SECONDARY outcome

Timeframe: Nights 13-14

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

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).

Outcome measures

Measure	Ramelteon 1 mg QD n=30 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=32 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=32 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Latency to Persistent Sleep Over a 2-night Average Measured by Polysomnography (Nights 13-14)	48.36 minutes Standard Error 6.849	38.61 minutes Standard Error 6.611	45.29 minutes Standard Error 6.732	46.64 minutes Standard Error 6.983

SECONDARY outcome

Timeframe: Nights 6-7

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

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

Outcome measures

Measure	Ramelteon 1 mg QD n=31 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=33 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=33 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Total Sleep Time Over a 2-night Average Measured by Polysomnography (Nights 6-7)	376.41 minutes Standard Error 8.158	383.51 minutes Standard Error 7.876	378.62 minutes Standard Error 8.033	366.23 minutes Standard Error 8.421

SECONDARY outcome

Timeframe: Nights 13-14

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

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

Outcome measures

Measure	Ramelteon 1 mg QD n=30 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=32 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=32 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Total Sleep Time Over a 2-night Average Measured by Polysomnography (Nights 13-14)	389.72 minutes Standard Error 8.866	378.04 minutes Standard Error 8.683	379.17 minutes Standard Error 8.843	388.51 minutes Standard Error 9.064

SECONDARY outcome

Timeframe: Nights 6-7

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

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

Outcome measures

Measure	Ramelteon 1 mg QD n=31 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=33 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=33 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Sleep Efficiency Over a 2-night Average Measured by Polysomnography (0-3 Hours) (Nights 6-7)	64.49 percentage of time asleep Standard Error 3.385	71.83 percentage of time asleep Standard Error 3.213	65.70 percentage of time asleep Standard Error 3.272	64.64 percentage of time asleep Standard Error 3.460

SECONDARY outcome

Timeframe: Nights 13-14

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

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

Outcome measures

Measure	Ramelteon 1 mg QD n=30 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=32 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=32 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Sleep Efficiency Over a 2-night Average Measured by Polysomnography (0-3 Hours) (Nights 13-14)	69.07 percentage of time asleep Standard Error 3.244	75.13 percentage of time asleep Standard Error 3.126	70.19 percentage of time asleep Standard Error 3.181	70.99 percentage of time asleep Standard Error 3.286

SECONDARY outcome

Timeframe: Nights 6-7

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

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

Outcome measures

Measure	Ramelteon 1 mg QD n=31 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=33 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=33 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Sleep Efficiency Over a 2-night Average Measured by Polysomnography (0-8 Hours) (Nights 6-7)	78.42 percentage of time asleep Standard Error 1.701	79.90 percentage of time asleep Standard Error 1.642	78.89 percentage of time asleep Standard Error 1.675	76.30 percentage of time asleep Standard Error 1.756

SECONDARY outcome

Timeframe: Nights 13-14

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

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

Outcome measures

Measure	Ramelteon 1 mg QD n=30 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=32 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=32 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Sleep Efficiency Over a 2-night Average Measured by Polysomnography (0-8 Hours) (Nights 13-14)	81.09 percentage of time asleep Standard Error 1.706	79.33 percentage of time asleep Standard Error 1.671	78.92 percentage of time asleep Standard Error 1.702	80.80 percentage of time asleep Standard Error 1.745

SECONDARY outcome

Timeframe: Nights 6-7

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

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

Outcome measures

Measure	Ramelteon 1 mg QD n=31 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=33 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=33 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Wake Time After Sleep Onset Over a 2-night Average Measured by Polysomnography (Nights 6-7)	46.26 minutes Standard Error 5.880	62.86 minutes Standard Error 5.704	51.06 minutes Standard Error 5.758	62.11 minutes Standard Error 6.035

SECONDARY outcome

Timeframe: Nights 13-14

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

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

Outcome measures

Measure	Ramelteon 1 mg QD n=30 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=32 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=32 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Wake Time After Sleep Onset Over a 2-night Average Measured by Polysomnography (Nights 13-14)	43.36 minutes Standard Error 6.124	63.47 minutes Standard Error 6.032	59.77 minutes Standard Error 6.103	48.88 minutes Standard Error 6.240

SECONDARY outcome

Timeframe: Nights 6-7

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=31 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=33 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=33 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Number of Awakenings Over a 2-night Average Measured by Polysomnography (Nights 6-7)	9.22 number of awakenings Standard Error 0.835	10.79 number of awakenings Standard Error 0.795	10.79 number of awakenings Standard Error 0.815	9.67 number of awakenings Standard Error 0.853

SECONDARY outcome

Timeframe: Nights 13-14

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=30 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=32 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=32 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Number of Awakenings Over a 2-night Average Measured by Polysomnography (Nights 13-14)	8.08 number of awakenings Standard Error 0.806	9.33 number of awakenings Standard Error 0.783	9.87 number of awakenings Standard Error 0.800	9.51 number of awakenings Standard Error 0.822

SECONDARY outcome

Timeframe: Nights 6-7

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

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

Outcome measures

Measure	Ramelteon 1 mg QD n=31 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=33 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=33 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Total Wake Time Over a 2-night Average Measured by Polysomnography (Nights 6-7)	63.92 minutes Standard Error 6.096	50.67 minutes Standard Error 5.785	61.67 minutes Standard Error 5.892	63.63 minutes Standard Error 6.230

SECONDARY outcome

Timeframe: Nights 13-14

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

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

Outcome measures

Measure	Ramelteon 1 mg QD n=30 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=32 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=32 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Total Wake Time Over a 2-night Average Measured by Polysomnography (Nights 13-14)	55.69 minutes Standard Error 5.841	44.68 minutes Standard Error 5.629	53.64 minutes Standard Error 5.728	52.19 minutes Standard Error 5.918

SECONDARY outcome

Timeframe: Nights 6-7

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=31 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=33 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=33 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Sleep Time Over a 2-night Average Measured by Polysomnography (Nights 6-7)	22.40 hours on a 24-hour clock Standard Error 0.016	22.36 hours on a 24-hour clock Standard Error 0.016	22.35 hours on a 24-hour clock Standard Error 0.016	22.35 hours on a 24-hour clock Standard Error 0.033

SECONDARY outcome

Timeframe: Nights 13-14

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=30 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=32 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=32 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Sleep Time Over a 2-night Average Measured by Polysomnography (Nights 13-14)	22.36 hours on a 24-hour clock Standard Error 0.016	22.36 hours on a 24-hour clock Standard Error 0.016	22.36 hours on a 24-hour clock Standard Error 0.016	22.33 hours on a 24-hour clock Standard Error 0.016

SECONDARY outcome

Timeframe: Nights 6-7

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=31 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=33 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=33 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Wake Time Over a 2-night Average Measured by Polysomnography (Nights 6-7)	06.35 hours on a 24-hour clock Standard Error 0.033	06.31 hours on a 24-hour clock Standard Error 0.033	06.30 hours on a 24-hour clock Standard Error 0.033	06.26 hours on a 24-hour clock Standard Error 0.033

SECONDARY outcome

Timeframe: Nights 13-14

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=30 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=32 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=32 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Wake Time Over a 2-night Average Measured by Polysomnography (Nights 13-14)	06.31 hours on a 24-hour clock Standard Error 0.066	06.21 hours on a 24-hour clock Standard Error 0.066	06.40 hours on a 24-hour clock Standard Error 0.066	06.26 hours on a 24-hour clock Standard Error 0.083

SECONDARY outcome

Timeframe: Nights 6-7

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=26 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=28 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=28 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=29 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Total Sleep Time Measured by Actigraphy (Nights 6-7)	374.37 minutes Standard Error 8.741	393.37 minutes Standard Error 8.632	370.83 minutes Standard Error 8.352	369.05 minutes Standard Error 8.457

SECONDARY outcome

Timeframe: Nights 13-14

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=26 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=27 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=30 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=27 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Total Sleep Time Measured by Actigraphy (Nights 13-14)	391.61 minutes Standard Error 8.661	390.76 minutes Standard Error 8.982	370.80 minutes Standard Error 8.228	378.91 minutes Standard Error 8.845

SECONDARY outcome

Timeframe: Nights 6-7

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=26 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=28 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=28 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=29 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Sleep Efficiency Measured by Actigraphy (Nights 6-7)	85.79 percentage of time asleep Standard Error 1.117	83.46 percentage of time asleep Standard Error 1.086	81.38 percentage of time asleep Standard Error 1.081	82.72 percentage of time asleep Standard Error 1.089

SECONDARY outcome

Timeframe: Nights 13-14

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=26 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=27 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=30 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=27 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Sleep Efficiency Measured by Actigraphy (Nights 13-14)	84.98 percentage of time asleep Standard Error 1.349	82.91 percentage of time asleep Standard Error 1.381	81.31 percentage of time asleep Standard Error 1.300	83.24 percentage of time asleep Standard Error 1.388

SECONDARY outcome

Timeframe: Nights 6-7

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=26 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=28 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=28 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=29 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Wake Time During Sleep Interval Measured by Actigraphy (Nights 6-7)	41.81 minutes Standard Error 4.404	51.98 minutes Standard Error 4.298	54.70 minutes Standard Error 4.211	53.14 minutes Standard Error 4.223

SECONDARY outcome

Timeframe: Nights 13-14

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=26 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=27 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=30 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=27 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Wake Time During Sleep Interval Measured by Actigraphy (Nights 13-14)	48.11 minutes Standard Error 4.074	54.72 minutes Standard Error 4.185	52.36 minutes Standard Error 3.874	51.32 minutes Standard Error 4.140

SECONDARY outcome

Timeframe: Nights 6-7

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=26 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=28 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=28 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=29 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Wake Bouts Measured by Actigraphy (Nights 6-7)	20.98 wake bouts Standard Error 1.518	22.91 wake bouts Standard Error 1.476	23.32 wake bouts Standard Error 1.457	22.82 wake bouts Standard Error 1.442

SECONDARY outcome

Timeframe: Nights 13-14

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=26 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=27 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=30 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=27 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Wake Bouts Measured by Actigraphy (Nights 13-14)	23.42 wake bouts Standard Error 1.201	24.21 wake bouts Standard Error 1.230	23.52 wake bouts Standard Error 1.146	22.78 wake bouts Standard Error 1.206

SECONDARY outcome

Timeframe: Nights 6-7

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

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).

Outcome measures

Measure	Ramelteon 1 mg QD n=26 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=28 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=28 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=29 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Sleep Latency Measured by Actigraphy (Nights 6-7)	12.53 minutes Standard Error 3.292	18.05 minutes Standard Error 3.280	25.00 minutes Standard Error 3.156	12.42 minutes Standard Error 3.129

SECONDARY outcome

Timeframe: Nights 13-14

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

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).

Outcome measures

Measure	Ramelteon 1 mg QD n=26 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=27 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=30 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=27 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Sleep Latency Measured by Actigraphy (Nights 13-14)	12.10 minutes Standard Error 6.145	16.40 minutes Standard Error 6.460	25.43 minutes Standard Error 5.859	12.36 minutes Standard Error 6.169

SECONDARY outcome

Timeframe: Nights 6-7

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=26 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=28 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=28 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=29 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Sleep Time Measured by Actigraphy (Nights 6-7)	23.28 hours on a 24-hour clock Standard Error 0.150	22.75 hours on a 24-hour clock Standard Error 0.150	23.11 hours on a 24-hour clock Standard Error 0.150	23.31 hours on a 24-hour clock Standard Error 0.150

SECONDARY outcome

Timeframe: Nights 13-14

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=26 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=27 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=30 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=27 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Sleep Time Measured by Actigraphy (Nights 13-14)	22.83 hours on a 24-hour clock Standard Error 0.150	22.71 hours on a 24-hour clock Standard Error 0.166	23.11 hours on a 24-hour clock Standard Error 0.150	23.18 hours on a 24-hour clock Standard Error 0.150

SECONDARY outcome

Timeframe: Nights 6-7

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=26 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=28 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=28 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=29 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Wake Time Measured by Actigraphy (Nights 6-7)	06.20 hours on a 24-hour clock Standard Error 0.116	06.18 hours on a 24-hour clock Standard Error 0.116	06.23 hours on a 24-hour clock Standard Error 0.116	06.36 hours on a 24-hour clock Standard Error 0.116

SECONDARY outcome

Timeframe: Nights 13-14

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=26 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=27 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=30 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=27 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Wake Time Measured by Actigraphy (Nights 13-14)	06.13 hours on a 24-hour clock Standard Error 0.133	06.08 hours on a 24-hour clock Standard Error 0.133	06.16 hours on a 24-hour clock Standard Error 0.133	06.30 hours on a 24-hour clock Standard Error 0.133

SECONDARY outcome

Timeframe: Nights 6-7

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

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?"

Outcome measures

Measure	Ramelteon 1 mg QD n=31 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=33 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=34 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Subjective Sleep Latency Measured by a Post-sleep Questionnaire (Nights 6-7)	103.55 minutes Standard Error 8.301	84.46 minutes Standard Error 8.087	92.79 minutes Standard Error 7.930	97.28 minutes Standard Error 8.491

SECONDARY outcome

Timeframe: Nights 13-14

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

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?"

Outcome measures

Measure	Ramelteon 1 mg QD n=28 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=29 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=32 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Subjective Sleep Latency Measured by a Post-sleep Questionnaire (Nights 13-14)	80.57 minutes Standard Error 7.406	69.40 minutes Standard Error 7.423	77.29 minutes Standard Error 7.178	74.75 minutes Standard Error 7.407

SECONDARY outcome

Timeframe: Nights 6-7

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

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?"

Outcome measures

Measure	Ramelteon 1 mg QD n=31 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=33 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=34 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Subjective Total Sleep Time Measured by a Post-sleep Questionnaire (Nights 6-7)	348.10 minutes Standard Error 10.302	370.14 minutes Standard Error 10.067	360.57 minutes Standard Error 9.883	341.76 minutes Standard Error 10.571

SECONDARY outcome

Timeframe: Nights 13-14

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

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?"

Outcome measures

Measure	Ramelteon 1 mg QD n=28 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=29 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=32 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Subjective Total Sleep Time Measured by a Post-sleep Questionnaire (Nights 13-14)	379.20 minutes Standard Error 10.490	375.73 minutes Standard Error 10.532	365.14 minutes Standard Error 10.229	368.99 minutes Standard Error 10.513

SECONDARY outcome

Timeframe: Nights 6-7

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

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?"

Outcome measures

Measure	Ramelteon 1 mg QD n=31 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=33 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=34 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Subjective Wake Time After Sleep Onset Measured by a Post-sleep Questionnaire (Nights 6-7)	35.15 minutes Standard Error 7.084	52.52 minutes Standard Error 6.671	34.41 minutes Standard Error 6.659	47.84 minutes Standard Error 7.100

SECONDARY outcome

Timeframe: Nights 13-14

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

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?"

Outcome measures

Measure	Ramelteon 1 mg QD n=28 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=29 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=32 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Subjective Wake Time After Sleep Onset Measured by a Post-sleep Questionnaire (Nights 13-14)	23.49 minutes Standard Error 5.882	45.54 minutes Standard Error 5.877	28.66 minutes Standard Error 5.669	30.52 minutes Standard Error 5.794

SECONDARY outcome

Timeframe: Nights 6-7

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

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?"

Outcome measures

Measure	Ramelteon 1 mg QD n=25 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=27 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=21 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=22 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Subjective Number of Awakenings Measured by a Post-sleep Questionnaire (Nights 6-7)	2.68 number of awakenings Standard Error 0.364	3.72 number of awakenings Standard Error 0.382	2.92 number of awakenings Standard Error 0.385	3.23 number of awakenings Standard Error 0.383

SECONDARY outcome

Timeframe: Nights 13-14

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

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?"

Outcome measures

Measure	Ramelteon 1 mg QD n=19 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=22 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=21 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=22 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Subjective Number of Awakenings Measured by a Post-sleep Questionnaire (Nights 13-14)	2.94 number of awakenings Standard Error 0.456	3.72 number of awakenings Standard Error 0.427	3.33 number of awakenings Standard Error 0.443	3.04 number of awakenings Standard Error 0.423

SECONDARY outcome

Timeframe: Nights 6-7

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=31 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=33 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=34 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Subjective Sleep Quality Measured by a Post-sleep Questionnaire (Nights 6-7)	4.45 scores on a scale Standard Error 0.169	4.61 scores on a scale Standard Error 0.166	4.33 scores on a scale Standard Error 0.162	4.74 scores on a scale Standard Error 0.173

SECONDARY outcome

Timeframe: Nights 13-14

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=28 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=29 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=32 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Subjective Sleep Quality Measured by a Post-sleep Questionnaire (Nights 13-14)	4.27 scores on a scale Standard Error 0.184	4.35 scores on a scale Standard Error 0.185	4.03 scores on a scale Standard Error 0.179	4.20 scores on a scale Standard Error 0.184

SECONDARY outcome

Timeframe: Nights 6-7

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=31 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=33 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=34 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Subjective Sleep Time Measured by a Post-sleep Questionnaire (Nights 6-7)	10.36 hours on a 24-hour clock Standard Error 0.066	10.41 hours on a 24-hour clock Standard Error 0.066	10.40 hours on a 24-hour clock Standard Error 0.066	10.40 hours on a 24-hour clock Standard Error 0.066

SECONDARY outcome

Timeframe: Nights 13-14

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=28 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=29 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=32 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Subjective Sleep Time Measured by a Post-sleep Questionnaire (Nights 13-14)	10.36 hours on a 24-hour clock Standard Error 0.066	10.30 hours on a 24-hour clock Standard Error 0.066	10.36 hours on a 24-hour clock Standard Error 0.066	10.40 hours on a 24-hour clock Standard Error 0.066

SECONDARY outcome

Timeframe: Nights 6-7

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=25 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=29 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=31 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=24 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Subjective Getting up in the Morning Measured by a Post-sleep Questionnaire (Nights 6-7)	4.68 scores on a scale Standard Error 0.224	4.76 scores on a scale Standard Error 0.202	4.67 scores on a scale Standard Error 0.178	4.88 scores on a scale Standard Error 0.203

SECONDARY outcome

Timeframe: Nights 13-14

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=24 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=23 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=26 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=25 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Subjective Getting up in the Morning Measured by a Post-sleep Questionnaire (Nights 13-14)	4.46 scores on a scale Standard Error 0.219	4.66 scores on a scale Standard Error 0.217	4.30 scores on a scale Standard Error 0.191	4.28 scores on a scale Standard Error 0.198

SECONDARY outcome

Timeframe: Nights 6-7

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=31 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=33 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=34 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Subjective Ability to Concentrate in the Morning Measured by a Post-sleep Questionnaire (Nights 6-7)	4.31 scores on a scale Standard Error 0.155	4.30 scores on a scale Standard Error 0.151	4.40 scores on a scale Standard Error 0.148	4.48 scores on a scale Standard Error 0.159

SECONDARY outcome

Timeframe: Nights 13-14

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=28 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=29 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=32 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Subjective Ability to Concentrate in the Morning Measured by a Post-sleep Questionnaire (Nights 13-14)	3.77 scores on a scale Standard Error 0.164	4.17 scores on a scale Standard Error 0.164	4.01 scores on a scale Standard Error 0.159	4.01 scores on a scale Standard Error 0.164

SECONDARY outcome

Timeframe: Nights 6-7

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=31 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=31 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=34 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Subjective Level of Alertness Measured by a Post-sleep Questionnaire (Nights 6-7)	4.43 scores on a scale Standard Error 0.158	4.32 scores on a scale Standard Error 0.155	4.33 scores on a scale Standard Error 0.152	4.53 scores on a scale Standard Error 0.163

SECONDARY outcome

Timeframe: Nights 13-14

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=28 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=29 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=32 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Subjective Level of Alertness Measured by a Post-sleep Questionnaire (Nights 13-14)	4.02 scores on a scale Standard Error 0.181	4.32 scores on a scale Standard Error 0.181	3.99 scores on a scale Standard Error 0.176	4.12 scores on a scale Standard Error 0.182

SECONDARY outcome

Timeframe: Day 15

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=30 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=31 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=32 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=29 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Next Morning Residual Effects Assessments of Psychomotor and Cognitive Function Via Digit Symbol Substitution Test	44.1 Scores on a scale Standard Error 1.77	42.4 Scores on a scale Standard Error 1.74	39.9 Scores on a scale Standard Error 1.74	40.6 Scores on a scale Standard Error 1.83

SECONDARY outcome

Timeframe: Day 15

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=30 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=30 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=32 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=29 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Next Morning Residual Effects Assessments of Psychomotor and Cognitive Function Via Memory Recall Test--Immediate	8.1 score Standard Error 0.39	7.7 score Standard Error 0.40	8.6 score Standard Error 0.39	8.6 score Standard Error 0.41

SECONDARY outcome

Timeframe: Day 15

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=30 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=30 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=32 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=29 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Next Morning Residual Effects Assessments of Psychomotor and Cognitive Function Via Memory Recall Test--Delayed	6.5 score Standard Error 0.51	5.9 score Standard Error 0.51	6.7 score Standard Error 0.50	7.1 score Standard Error 0.52

SECONDARY outcome

Timeframe: Day 15

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=30 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=31 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=32 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=29 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Visual Analogue Scale for Mood	34.2 Units on a scale Standard Error 3.20	33.4 Units on a scale Standard Error 3.15	34.3 Units on a scale Standard Error 3.17	33.4 Units on a scale Standard Error 3.31

SECONDARY outcome

Timeframe: Day 15

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=30 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=31 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=32 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=30 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Visual Analogue Scale for Feelings	37.3 Units on a scale Standard Error 1.52	34.8 Units on a scale Standard Error 1.50	36.8 Units on a scale Standard Error 1.50	36.9 Units on a scale Standard Error 1.57

SECONDARY outcome

Timeframe: Day 15

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=25 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=29 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=31 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=25 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
The Time of Dim Light Melatonin Secretion Onset	21.40 hours on a 24-hour clock Standard Error 0.183	21.30 hours on a 24-hour clock Standard Error 0.166	20.93 hours on a 24-hour clock Standard Error 0.166	21.21 hours on a 24-hour clock Standard Error 0.200

SECONDARY outcome

Timeframe: Day 15

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

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.

Outcome measures

Measure	Ramelteon 1 mg QD n=25 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=29 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=31 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=25 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
The Time of Dim Light Melatonin Secretion Offset	11.21 hours on a 24-hour clock Standard Error 0.250	10.73 hours on a 24-hour clock Standard Error 0.250	10.96 hours on a 24-hour clock Standard Error 0.250	10.85 hours on a 24-hour clock Standard Error 0.283

SECONDARY outcome

Timeframe: Day 15

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

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

Outcome measures

Measure	Ramelteon 1 mg QD n=25 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=29 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=31 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=25 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
The Total Duration of Secretion of Melatonin	1021.8 minutes Standard Error 34.13	1003.1 minutes Standard Error 31.98	980.2 minutes Standard Error 31.43	1027.9 minutes Standard Error 36.39

SECONDARY outcome

Timeframe: Day 15

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

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

Outcome measures

Measure	Ramelteon 1 mg QD n=25 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=29 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=31 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=25 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
The Area Under the Concentration-time Curve of Melatonin From 0 to 24 Hours	608.5 μg/dL/hour Standard Error 40.13	563.3 μg/dL/hour Standard Error 38.08	528.3 μg/dL/hour Standard Error 37.35	631.5 μg/dL/hour Standard Error 42.77

SECONDARY outcome

Timeframe: Day 15

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

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

Outcome measures

Measure	Ramelteon 1 mg QD n=25 Participants Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=29 Participants Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=31 Participants Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=25 Participants Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Average Cmax (Maximum Observed Plasma Concentration) Calculated as the Average of Three Highest Cmax Observations Within the Sampling Period.	75.3 μg/dL Standard Error 5.12	69.3 μg/dL Standard Error 4.84	65.2 μg/dL Standard Error 4.77	79.2 μg/dL Standard Error 5.46

Adverse Events

Ramelteon 1 mg QD

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Ramelteon 4 mg QD

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Ramelteon 8 mg QD

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo QD

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Ramelteon 1 mg QD n=32 participants at risk Ramelteon 1 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 4 mg QD n=33 participants at risk Ramelteon 4 mg, tablets, orally, once daily for up to 2 weeks.	Ramelteon 8 mg QD n=35 participants at risk Ramelteon 8 mg, tablets, orally, once daily for up to 2 weeks.	Placebo QD n=32 participants at risk Ramelteon placebo-matching tablets, orally, once daily for up to 2 weeks.
Investigations Blood Creatine Phosphokinase Increased	3.1% 1/32 There were no Serious Adverse Events	0.00% 0/33 There were no Serious Adverse Events	5.7% 2/35 There were no Serious Adverse Events	3.1% 1/32 There were no Serious Adverse Events
Musculoskeletal and connective tissue disorders Pain in Extremity	0.00% 0/32 There were no Serious Adverse Events	6.1% 2/33 There were no Serious Adverse Events	0.00% 0/35 There were no Serious Adverse Events	0.00% 0/32 There were no Serious Adverse Events
Nervous system disorders Headache	12.5% 4/32 There were no Serious Adverse Events	3.0% 1/33 There were no Serious Adverse Events	8.6% 3/35 There were no Serious Adverse Events	3.1% 1/32 There were no Serious Adverse Events
Nervous system disorders Somnolence	6.2% 2/32 There were no Serious Adverse Events	6.1% 2/33 There were no Serious Adverse Events	2.9% 1/35 There were no Serious Adverse Events	6.2% 2/32 There were no Serious Adverse Events

Additional Information

Sr. VP, Clinical Science

Takeda Global Research and Development Center, Inc.

Phone: 800-778-2860

Email: clinicaltrialregistry@tpna.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER