Ramelteon 8 mg Tablets Specified Drug-use Survey: <Long-term Survey on Insomnia Accompanied by Difficulty Falling Asleep> - Transitional Survey From the Preceding Drug-use Survey -

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02153086
• Collaborator: (none)
• Enrollment: 236
• Locations: 2
• Duration (Months): 39
• Patients Per Site: 118
• Patients Per Site Per Month: 3

Study Details

Study Description

Brief Summary

The purpose of this survey is to examine the safety and efficacy of long-term use of ramelteon tablets (Rozerem 8 mg Tablets) in participants with difficulty falling asleep associated with insomnia in daily medical practice.

Condition or Disease	Intervention/Treatment	Phase
Insomnia	Drug: Ramelteon

Detailed Description

This survey was designed to examine the safety and efficacy of long-term use of ramelteon tablets (Rozerem 8 mg Tablets) in participants with difficulty falling asleep associated with insomnia in daily medical practice.The usual dosage for adults is 8 mg of ramelteon administered orally once daily at bedtime.

Study Design

• Study Type: Observational
• Actual Enrollment: 236 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Rozerem 8 mg Tablets Specified Drug-use Survey: <Long-term Survey on Insomnia Associated With Sleep-onset Difficulty > - Transitional Survey From the Preceding Drug-use Survey -
• Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Ramelteon 8 mg Tablets	Drug: Ramelteon; Ramelteon tablets 8 mg; Other Names: Rozerem 8 mg Tablets

Outcome Measures

Primary Outcome Measures

1. Number of Participants Reporting One or More Adverse Drug Reactions [Baseline up to 12 months]

   Adverse drug reactions are defined as adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms or diseases temporally associated with the use of a medicinal product reported from the first dose of study drug to the last dose of study drug.

Secondary Outcome Measures

1. Sleep Status: Sleep Onset Latency [Baseline, Week 4 and Month 12]

   Sleep status was determined by measuring the sleep onset latency, defined as the length of time taken from lying down for the night until sleep onset. The data was assessed at baseline, Week 4 and final visit (last visit for a participant in the study, up to Month 12).

2. Sleep Status: Total Sleep Time [Baseline, Week 4 and Month 12]

   Sleep status was determined by measuring the total sleep time, defined as the amount of actual sleep time during a sleep episode. The data was assessed at baseline, Week 4 and final visit (last visit for a participant in the study, up to Month 12).

3. Sleep Status: Number of Awakenings [Baseline, Week 4 and Month 12]

   Sleep status of participants was assessed and summarized by calculating the number of times participants had awaken from the time of start of the investigation. The data was assessed at baseline, Week 4 and final visit (last visit for a participant in the study, up to Month 12).

4. Percentage of Participants Reported With Improvement on the Patient Global Impression (PGI) Scale for Sleep Onset [At Week 4, 52, and final assessment (up to 12 months)]

   Sleep onset was defined as the transition from wakefulness into sleep. PGI is a participant rated instrument to measure participant's change in overall status on a 7-point scale. Participants provide their response on a PGI questionnaire. Total score range from 1 (very much improved) to 7 (very much worse). Percentage of participants with improvement rated as "much better" or "a little better" were reported. The data was assessed at Week 4, Week 52 and final visit (follow up visit up to Month 12).

5. Percentage of Participants Reported With Improvement on the PGI Scale for Sleep Duration [At Week 4, 52, and final assessment (up to 12 months)]

   Sleep duration was defined as the total amount of sleep obtained. PGI is a participant rated instrument to measure participant's change in overall status on a 7-point scale. Participants provide their response on a PGI questionnaire. Total score range from 1 (very much improved) to 7 (very much worse). Percentage of participants with improvement rated as "much better" or "a little better" were reported. The data was assessed at Week 4, Week 52 and final visit (follow up visit up to Month 12).

6. Percentage of Participants Reported With Improvement on the PGI Scale for Sleep Quality [At Week 4, 52, and final assessment (up to 12 months)]

   Sleep quality was defined as participants satisfaction of the sleep experience, integrating aspects of sleep initiation, sleep maintenance, sleep quantity, and refreshment upon awakening. PGI is a participant rated instrument to measure participant's change in overall status on a 7-point scale. Participants provide their response on a PGI questionnaire. Total score range from 1 (very much improved) to 7 (very much worse). Percentage of participants with improvement rated as "much better" or "a little better" were reported. The data was assessed at Week 4, Week 52 and final visit (follow up visit up to Month 12).

7. Percentage of Participants Reported With Improvement on the PGI Scale for Morning Awakening [At Week 4, 52, and final assessment (up to 12 months)]

   Morning awakening was defined as the return to the awaked state from any non-rapid eye movement (NREM) to rapid eye movement (REM) sleep stages in the morning. PGI is a participant rated instrument to measure participant's change in overall status on a 7-point scale. Participants provide their response on a PGI questionnaire. Total score range from 1 (very much improved) to 7 (very much worse). Percentage of participants with improvement rated as "much better" or "a little better" were reported. The data was assessed at Week 4, Week 52 and final visit (follow up visit up to Month 12).

8. Percentage of Participants Reported With Improvement on the PGI Scale for Remaining Tiredness in the Morning [At Week 4, 52, and final assessment (up to 12 months)]

   Remaining tiredness in the morning was defined as an experience of fatigue after complete or adequate sleep duration. PGI is a participant rated instrument to measure participant's change in overall status on a 7-point scale. Participants provide their response on a PGI questionnaire. Total score range from 1 (very much improved) to 7 (very much worse). Percentage of participants with improvement rated as "much better" or "a little better" were reported. The data was assessed at Week 4, Week 52 and final visit (follow up visit up to Month 12).

9. Percentage of Participants Reported With Improvement on the PGI Scale for Daytime Somnolence [At Week 4, 52, and final assessment (up to 12 months)]

   Daytime somnolence was defined as excessive daytime sleepiness (EDS), characterized by general lack of energy, even after adequate or prolonged night time sleep. PGI is a participant rated instrument to measure participant's change in overall status on a 7-point scale. Participants provide their response on a PGI questionnaire. Total score range from 1 (very much improved) to 7 (very much worse). Percentage of participants with improvement rated as "much better" or "a little better" were reported. The data was assessed at Week 4, Week 52 and final visit (follow up visit up to Month 12).

10. Percentage of Participants Reported With Improvement on the PGI Scale for Daytime Physical Condition/Function [At Week 4, 52, and final assessment (up to 12 months)]

    Daytime physical condition/function was defined as general condition of participant throughout the day after adequate or prolonged night time sleep. PGI is a participant rated instrument to measure participant's change in overall status on a 7-point scale. Participants provide their response on a PGI questionnaire. Total score range from 1 (very much improved) to 7 (very much worse). Percentage of participants with improvement rated as "much better" or "a little better" were reported. The data was assessed at Week 4, Week 52 and final visit (follow up visit up to Month 12).

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

-Participants with difficulty falling asleep associated with insomnia who have completed a 4-week follow-up in the preceding drug use surveillance and are able to receive continuous administration of Rozerem Tablets

Exclusion Criteria:

• Participants with contraindications to Rozerem Tablets.

• Participants with previous history of hypersensitivity to ingredients in Rozerem Tablets.

• Participants with severe liver dysfunction.

• Participants taking fluvoxamine maleate

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Osaka		Japan
2		Tokyo		Japan

Sponsors and Collaborators

• Takeda

Investigators

• Study Chair: Postmarketing Group Manager, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT02153086
• Other Study ID Numbers: 293-011
• First Posted: Jun 2, 2014
• Last Update Posted: Oct 13, 2016
• Last Verified: Aug 1, 2016

• Keywords provided by Takeda: Pharmacological therapy
• Additional relevant MeSH terms: Sleep Initiation and Maintenance Disorders

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 2 investigative sites in Japan from 01 March 2011 to 30 June 2014.
Pre-assignment Detail	Participants with a historical diagnosis of insomnia which was associated with difficulty in falling asleep in daily clinical practice were enrolled in a single treatment group to receive ramelteon 8 milligram (mg).

Arm/Group Title	Ramelteon 8 mg
Arm/Group Description	Participants receiving ramelteon 8 mg, tablet, orally, once as daily clinical practice were observed for up to 6 months. A follow up of 6 months was carried out.
Period Title: Overall Study
STARTED	236
COMPLETED	232
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Ramelteon 8 mg
Arm/Group Description	Participants receiving ramelteon 8 mg, tablet, orally, once as daily clinical practice were observed for up to 6 months. A follow up of 6 months was carried out.
Overall Participants	232
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.1 (18.6)
Sex: Female, Male (Count of Participants)
Female	139 59.9%
Male	93 40.1%
Type of sleep disorders (Major symptoms) (participants) [Number]
Difficulty falling asleep	127 54.7%
Difficulty getting sound sleep	16 6.9%
Difficulty staying asleep	44 19%
Early morning awakening	2 0.9%
Unknown	43 18.5%
Degree of sleep disorders (participants) [Number]
Mild	72 31%
Moderate	130 56%
Severe	30 12.9%
Duration of insomnia (participants) [Number]
Less than (<) 1 year	102 (2.71) 44%
Greater than equal to (>=) 1 year to <3 years	15 6.5%
>=3 to <5 years	14 6%
>=5 years	11 4.7%
Unknown	90 38.8%
Presence of complications (participants) [Number]
Had Complications	193 83.2%
Had No Complications	39 16.8%
Breakdown of complications (participants) [Number]
Hypertension	86 37.1%
Dyslipidaemia	57 24.6%
Mental disease	32 13.8%
Allergic disease	23 9.9%
Diabetes mellitus	22 9.5%
Heart or cerebrovascular disease	22 9.5%
Renal and urinary disorders	17 7.3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Reporting One or More Adverse Drug Reactions
Description	Adverse drug reactions are defined as adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms or diseases temporally associated with the use of a medicinal product reported from the first dose of study drug to the last dose of study drug.
Time Frame	Baseline up to 12 months

Outcome Measure Data

Analysis Population Description

The safety analysis set was defined as all participants who were enrolled and completed the study.

Arm/Group Title	Ramelteon 8 mg
Arm/Group Description	Participants receiving ramelteon 8 mg, tablet, orally, once as daily clinical practice were observed for up to 6 months. A follow up of 6 months was carried out.
Measure Participants	232
Number [participants]	0 0%

2. Secondary Outcome

Title	Sleep Status: Sleep Onset Latency
Description	Sleep status was determined by measuring the sleep onset latency, defined as the length of time taken from lying down for the night until sleep onset. The data was assessed at baseline, Week 4 and final visit (last visit for a participant in the study, up to Month 12).
Time Frame	Baseline, Week 4 and Month 12

Outcome Measure Data

Analysis Population Description

The efficacy assessment population was defined as participants whose efficacy data at baseline and at least 1 post-baseline time points was available.

Arm/Group Title	Ramelteon 8 mg
Arm/Group Description	Participants receiving ramelteon 8 mg, tablet, orally, once as daily clinical practice were observed for up to 6 months. A follow up of 6 months was carried out.
Measure Participants	207
Baseline (n=143)	98.7 (73.3)
At Week 4 (n=109)	48.3 (57.6)
At Final Assessment (n=127)	38.9 (39.4)

3. Secondary Outcome

Title	Sleep Status: Total Sleep Time
Description	Sleep status was determined by measuring the total sleep time, defined as the amount of actual sleep time during a sleep episode. The data was assessed at baseline, Week 4 and final visit (last visit for a participant in the study, up to Month 12).
Time Frame	Baseline, Week 4 and Month 12

Outcome Measure Data

Analysis Population Description

The efficacy assessment population was defined as participants whose efficacy data at baseline and at least 1 post-baseline time points was available.

Arm/Group Title	Ramelteon 8 mg
Arm/Group Description	Participants receiving ramelteon 8 mg, tablet, orally, once as daily clinical practice were observed for up to 6 months. A follow up of 6 months was carried out.
Measure Participants	207
Baseline (n=137)	6.74 (2.11)
At Week 4 (n=102)	7.51 (1.64)
At Final Assessment (n=120)	7.46 (1.72)

4. Secondary Outcome

Title	Sleep Status: Number of Awakenings
Description	Sleep status of participants was assessed and summarized by calculating the number of times participants had awaken from the time of start of the investigation. The data was assessed at baseline, Week 4 and final visit (last visit for a participant in the study, up to Month 12).
Time Frame	Baseline, Week 4 and Month 12

Outcome Measure Data

Analysis Population Description

The efficacy assessment population was defined as participants whose efficacy data at baseline and at least 1 post-baseline time points was available.

Arm/Group Title	Ramelteon 8 mg
Arm/Group Description	Participants receiving ramelteon 8 mg, tablet, orally, once as daily clinical practice were observed for up to 6 months. A follow up of 6 months was carried out.
Measure Participants	207
Baseline (n=150)	2.3 (1.5)
At Week 4 (n=115)	1.2 (1.2)
At Final Assessment (n=136)	1.1 (1.1)

5. Secondary Outcome

Title	Percentage of Participants Reported With Improvement on the Patient Global Impression (PGI) Scale for Sleep Onset
Description	Sleep onset was defined as the transition from wakefulness into sleep. PGI is a participant rated instrument to measure participant's change in overall status on a 7-point scale. Participants provide their response on a PGI questionnaire. Total score range from 1 (very much improved) to 7 (very much worse). Percentage of participants with improvement rated as "much better" or "a little better" were reported. The data was assessed at Week 4, Week 52 and final visit (follow up visit up to Month 12).
Time Frame	At Week 4, 52, and final assessment (up to 12 months)

Outcome Measure Data

Analysis Population Description

The efficacy assessment population was defined as participants whose efficacy data at baseline and at least 1 post-baseline time points was available.

Arm/Group Title	Ramelteon 8 mg
Arm/Group Description	Participants receiving ramelteon 8 mg, tablet, orally, once as daily clinical practice were observed for up to 6 months. A follow up of 6 months was carried out.
Measure Participants	207
At Week 4 (n=207)	80.2 (1.5) 34.6%
At Week 52 (n=88)	93.2 (1.2) 40.2%
At Final Assessment (n=207)	85.5 (1.1) 36.9%

6. Secondary Outcome

Title	Percentage of Participants Reported With Improvement on the PGI Scale for Sleep Duration
Description	Sleep duration was defined as the total amount of sleep obtained. PGI is a participant rated instrument to measure participant's change in overall status on a 7-point scale. Participants provide their response on a PGI questionnaire. Total score range from 1 (very much improved) to 7 (very much worse). Percentage of participants with improvement rated as "much better" or "a little better" were reported. The data was assessed at Week 4, Week 52 and final visit (follow up visit up to Month 12).
Time Frame	At Week 4, 52, and final assessment (up to 12 months)

Outcome Measure Data

Analysis Population Description

The efficacy assessment population was defined as participants whose efficacy data at baseline and at least 1 post-baseline time points was available.

Arm/Group Title	Ramelteon 8 mg
Arm/Group Description	Participants receiving ramelteon 8 mg, tablet, orally, once as daily clinical practice were observed for up to 6 months. A follow up of 6 months was carried out.
Measure Participants	207
At Week 4 (n=207)	77.8 (1.5) 33.5%
At Week 52 (n=88)	93.2 (1.2) 40.2%
At Final Assessment (n=207)	84.0 (1.1) 36.2%

7. Secondary Outcome

Title	Percentage of Participants Reported With Improvement on the PGI Scale for Sleep Quality
Description	Sleep quality was defined as participants satisfaction of the sleep experience, integrating aspects of sleep initiation, sleep maintenance, sleep quantity, and refreshment upon awakening. PGI is a participant rated instrument to measure participant's change in overall status on a 7-point scale. Participants provide their response on a PGI questionnaire. Total score range from 1 (very much improved) to 7 (very much worse). Percentage of participants with improvement rated as "much better" or "a little better" were reported. The data was assessed at Week 4, Week 52 and final visit (follow up visit up to Month 12).
Time Frame	At Week 4, 52, and final assessment (up to 12 months)

Outcome Measure Data

Analysis Population Description

The efficacy assessment population was defined as participants whose efficacy data at baseline and at least 1 post-baseline time points was available.

Arm/Group Title	Ramelteon 8 mg
Arm/Group Description	Participants receiving ramelteon 8 mg, tablet, orally, once as daily clinical practice were observed for up to 6 months. A follow up of 6 months was carried out.
Measure Participants	207
At Week 4 (n=207)	80.2 (1.5) 34.6%
At Week 52 (n=88)	93.2 (1.2) 40.2%
At Final Assessment (n=207)	86.0 (1.1) 37.1%

8. Secondary Outcome

Title	Percentage of Participants Reported With Improvement on the PGI Scale for Morning Awakening
Description	Morning awakening was defined as the return to the awaked state from any non-rapid eye movement (NREM) to rapid eye movement (REM) sleep stages in the morning. PGI is a participant rated instrument to measure participant's change in overall status on a 7-point scale. Participants provide their response on a PGI questionnaire. Total score range from 1 (very much improved) to 7 (very much worse). Percentage of participants with improvement rated as "much better" or "a little better" were reported. The data was assessed at Week 4, Week 52 and final visit (follow up visit up to Month 12).
Time Frame	At Week 4, 52, and final assessment (up to 12 months)

Outcome Measure Data

Analysis Population Description

The efficacy assessment population was defined as participants whose efficacy data at baseline and at least 1 post-baseline time points was available.

Arm/Group Title	Ramelteon 8 mg
Arm/Group Description	Participants receiving ramelteon 8 mg, tablet, orally, once as daily clinical practice were observed for up to 6 months. A follow up of 6 months was carried out.
Measure Participants	207
At Week 4 (n=207)	67.6 (1.5) 29.1%
At Week 52 (n=88)	87.5 (1.2) 37.7%
At Final Assessment (n=207)	77.8 (1.1) 33.5%

9. Secondary Outcome

Title	Percentage of Participants Reported With Improvement on the PGI Scale for Remaining Tiredness in the Morning
Description	Remaining tiredness in the morning was defined as an experience of fatigue after complete or adequate sleep duration. PGI is a participant rated instrument to measure participant's change in overall status on a 7-point scale. Participants provide their response on a PGI questionnaire. Total score range from 1 (very much improved) to 7 (very much worse). Percentage of participants with improvement rated as "much better" or "a little better" were reported. The data was assessed at Week 4, Week 52 and final visit (follow up visit up to Month 12).
Time Frame	At Week 4, 52, and final assessment (up to 12 months)

Outcome Measure Data

Analysis Population Description

The efficacy assessment population was defined as participants whose efficacy data at baseline and at least 1 post-baseline time points was available.

Arm/Group Title	Ramelteon 8 mg
Arm/Group Description	Participants receiving ramelteon 8 mg, tablet, orally, once as daily clinical practice were observed for up to 6 months. A follow up of 6 months was carried out.
Measure Participants	207
At Week 4 (n=207)	72.5 (1.5) 31.3%
At Week 52 (n=88)	81.8 (1.2) 35.3%
At Final Assessment (n=207)	77.3 (1.1) 33.3%

10. Secondary Outcome

Title	Percentage of Participants Reported With Improvement on the PGI Scale for Daytime Somnolence
Description	Daytime somnolence was defined as excessive daytime sleepiness (EDS), characterized by general lack of energy, even after adequate or prolonged night time sleep. PGI is a participant rated instrument to measure participant's change in overall status on a 7-point scale. Participants provide their response on a PGI questionnaire. Total score range from 1 (very much improved) to 7 (very much worse). Percentage of participants with improvement rated as "much better" or "a little better" were reported. The data was assessed at Week 4, Week 52 and final visit (follow up visit up to Month 12).
Time Frame	At Week 4, 52, and final assessment (up to 12 months)

Outcome Measure Data

Analysis Population Description

The efficacy assessment population was defined as participants whose efficacy data at baseline and at least 1 post-baseline time points was available.

Arm/Group Title	Ramelteon 8 mg
Arm/Group Description	Participants receiving ramelteon 8 mg, tablet, orally, once as daily clinical practice were observed for up to 6 months. A follow up of 6 months was carried out.
Measure Participants	207
At Week 4 (n=207)	65.2 (1.5) 28.1%
At Week 52 (n=88)	81.8 (1.2) 35.3%
At Final Assessment (n=207)	76.8 (1.1) 33.1%

11. Secondary Outcome

Title	Percentage of Participants Reported With Improvement on the PGI Scale for Daytime Physical Condition/Function
Description	Daytime physical condition/function was defined as general condition of participant throughout the day after adequate or prolonged night time sleep. PGI is a participant rated instrument to measure participant's change in overall status on a 7-point scale. Participants provide their response on a PGI questionnaire. Total score range from 1 (very much improved) to 7 (very much worse). Percentage of participants with improvement rated as "much better" or "a little better" were reported. The data was assessed at Week 4, Week 52 and final visit (follow up visit up to Month 12).
Time Frame	At Week 4, 52, and final assessment (up to 12 months)

Outcome Measure Data

Analysis Population Description

The efficacy assessment population was defined as participants whose efficacy data at baseline and at least 1 post-baseline time points was available.

Arm/Group Title	Ramelteon 8 mg
Arm/Group Description	Participants receiving ramelteon 8 mg, tablet, orally, once as daily clinical practice were observed for up to 6 months. A follow up of 6 months was carried out.
Measure Participants	207
At Week 4 (n=207)	70.5 (1.5) 30.4%
At Week 52 (n=88)	84.1 (1.2) 36.3%
At Final Assessment (n=207)	77.3 (1.1) 33.3%

Adverse Events

Time Frame	Baseline up to 12 months
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Only adverse drug reactions were analyzed in this study.
Arm/Group Title	Ramelteon 8 mg
Arm/Group Description	Participants receiving ramelteon 8 mg, tablet, orally, once as daily clinical practice were observed for up to 6 months. A follow up of 6 months was carried out.
All Cause Mortality
	Ramelteon 8 mg
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ramelteon 8 mg
	Affected / at Risk (%)	# Events
Total	0/232 (0%)
Other (Not Including Serious) Adverse Events
	Ramelteon 8 mg
	Affected / at Risk (%)	# Events
Total	0/232 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.