Ramelteon Tablets 8mg Drug Use Surveillance: Survey on Insomnia Associated With Sleep-onset Difficulty

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02058992
• Collaborator: (none)
• Enrollment: 3,339
• Duration (Months): 33

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate the safety and efficacy of ramelteon (Rozerem) when used in the routine clinical setting in patients with sleep-onset difficulty associated with insomnia.

Condition or Disease	Intervention/Treatment	Phase
Insomnia	Drug: Ramelteon

Detailed Description

This is a drug use surveillance planned to examine the safety and efficacy of ramelteon tablets when used in the routine clinical setting in patients with sleep-onset difficulty associated with insomnia (planned sample size, 3000)

The usual adult dosage is 8 mg of ramelteon administered orally once daily at bedtime.

Study Design

• Study Type: Observational
• Actual Enrollment: 3339 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Rozerem Tablets 8mg Drug Use Surveillance: Survey on Insomnia Associated With Sleep-onset Difficulty
• Study Start Date: Jul 1, 2010
• Actual Primary Completion Date: Apr 1, 2013
• Actual Study Completion Date: Apr 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Ramelteon 8 mg administered orally once daily	Drug: Ramelteon; Ramelteon 8 mg tablets; Other Names: Rozerem

Outcome Measures

Primary Outcome Measures

1. Number of Participants Reporting One or More Adverse Drug Reactions [Baseline up to 6 weeks]

   Adverse drug reactions are defined as adverse events (AE) which are in the investigator's opinion of causal relationship to the study treatment. AE 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.

2. Number of Participants Reporting One or More Serious Adverse Drug Reactions [Baseline up to 6 weeks]

   Serious adverse drug reactions are defined as serious adverse events (SAE) which are in the investigator's opinion of causal relationship to the study treatment. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Secondary Outcome Measures

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

   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.

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

   Sleep status was determined by measuring the total sleep time, defined as the amount of actual sleep time during a sleep episode.

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

   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.

4. Percentage of Participants Who Responded With Improvement on the Patient Global Impression (PGI) Scale at Week 4 [Week 4]

   PGI is a participant rated instrument to measure participant's change in overall status on a 7-point scale. 7 items on scale include sleep onset, sleep time, sleep quality, morning awakening, morning tiredness, daytime somnolence, and daytime physical condition/function. Participants provide their response on a PGI questionnaire. The results of survey using the PGI questionnaire was scored, summarized and assessed. 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 for sleep onset,time, quality; morning awakening, tiredness and daytime sleepiness, physical condition.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Sleep-onset difficulty associated with insomnia

Exclusion Criteria:

1. Patients with previous history of hypersensitivity to an ingredient of Rozerem Tablets

2. Patients with severe liver dysfunction

3. Patients taking fluvoxamine maleate

Contacts and Locations

Locations

No locations specified.

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: NCT02058992
• Other Study ID Numbers: 293-101; JapicCTI-132358; JapicCTI-R150751
• First Posted: Feb 11, 2014
• Last Update Posted: Jul 14, 2016
• Last Verified: Jun 1, 2016

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

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 557 investigative site in Japan from 30 July 2010 to 30 April 2013.
Pre-assignment Detail	Participants with a historical diagnosis of insomnia who were facing difficulty in falling asleep in daily clinical practice were enrolled in single treatment group to receive ramelteon 8 milligram (mg).

Arm/Group Title	Ramelteon
Arm/Group Description	Ramelteon 8 mg, tablets, orally, once as daily clinical practice were observed for up to 4 weeks. A follow up of 2 weeks was carried out.
Period Title: Overall Study
STARTED	3339
COMPLETED	3223
NOT COMPLETED	116

Baseline Characteristics

Arm/Group Title	Ramelteon
Arm/Group Description	Ramelteon 8 mg, tablets, orally, once as daily clinical practice were observed for up to 4 weeks. A follow up of 2 weeks was carried out.
Overall Participants	3223
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.5 (18.9)
Age, Customized (participants) [Number]
Less than (<) 65 years	1379 42.8%
Greater than or equal to (>=)65 years to <75 years	733 22.7%
>=75 years	1111 34.5%
Sex: Female, Male (Count of Participants)
Female	1935 60%
Male	1288 40%
Type of Sleep Disorder (Major Symptoms) (participants) [Number]
Difficulty falling asleep	1966 61%
Difficulty getting sound sleep	302 9.4%
Difficulty staying asleep	458 14.2%
Early morning awakening	50 1.6%
Unknown	447 13.9%
Degree of Sleep Disorder (participants) [Number]
Mild	1354 42%
Moderate	1569 48.7%
Severe	300 9.3%
Duration of Insomnia (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	1.13 (2.45)
Duration of Insomnia (participants) [Number]
< 1 year	1522 47.2%
>=1 year to <3 years	241 7.5%
>=3 to < 5 years	107 3.3%
>=5 years	135 4.2%
Unknown	1218 37.8%
Presence of Complications (participants) [Number]
Had Complications	2618 81.2%
Had No Complications	605 18.8%
Breakdown of complications (participants) [Number]
Hypertension	1206 37.4%
Dyslipidaemia	694 21.5%
Mental disease	495 15.4%
Diabetes mellitus	419 13%
Heart or cerebrovascular disease	393 12.2%
Renal and urinary disorders	158 4.9%
Hepatobiliary disorders	133 4.1%

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 (AE) which are in the investigator's opinion of causal relationship to the study treatment. AE 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 6 weeks

Outcome Measure Data

Analysis Population Description

Safety analysis set was defined as participants who were enrolled and completed the study.

Arm/Group Title	Ramelteon
Arm/Group Description	Ramelteon 8 mg, tablets, orally, once as daily clinical practice were observed for up to 4 weeks. A follow up of 2 weeks was carried out.
Measure Participants	3223
Number [participants]	109 3.4%

2. Primary Outcome

Title	Number of Participants Reporting One or More Serious Adverse Drug Reactions
Description	Serious adverse drug reactions are defined as serious adverse events (SAE) which are in the investigator's opinion of causal relationship to the study treatment. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time Frame	Baseline up to 6 weeks

Outcome Measure Data

Analysis Population Description

SAS was defined as participants who were enrolled and completed the study.

Arm/Group Title	Ramelteon
Arm/Group Description	Ramelteon 8 mg, tablets, orally, once as daily clinical practice were observed for up to 4 weeks. A follow up of 2 weeks was carried out.
Measure Participants	3223
Number [participants]	1 0%

3. 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.
Time Frame	Baseline and Week 4

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
Arm/Group Description	Ramelteon 8 mg, tablets, orally, once as daily clinical practice were observed for up to 4 weeks. A follow up of 2 weeks was carried out.
Measure Participants	1429
Baseline	89.8 (66.7)
Week 4	47.1 (46.2)

4. 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.
Time Frame	Baseline and Week 4

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
Arm/Group Description	Ramelteon 8 mg, tablets, orally, once as daily clinical practice were observed for up to 4 weeks. A follow up of 2 weeks was carried out.
Measure Participants	1292
Baseline	6.49 (2.00)
Week 4	7.31 (1.72)

5. 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.
Time Frame	Baseline and Week 4

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
Arm/Group Description	Ramelteon 8 mg, tablets, orally, once as daily clinical practice were observed for up to 4 weeks. A follow up of 2 weeks was carried out.
Measure Participants	1401
Baseline	2.1 (1.6)
Week 4	1.2 (1.2)

6. Secondary Outcome

Title	Percentage of Participants Who Responded With Improvement on the Patient Global Impression (PGI) Scale at Week 4
Description	PGI is a participant rated instrument to measure participant's change in overall status on a 7-point scale. 7 items on scale include sleep onset, sleep time, sleep quality, morning awakening, morning tiredness, daytime somnolence, and daytime physical condition/function. Participants provide their response on a PGI questionnaire. The results of survey using the PGI questionnaire was scored, summarized and assessed. 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 for sleep onset,time, quality; morning awakening, tiredness and daytime sleepiness, physical condition.
Time Frame	Week 4

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
Arm/Group Description	Ramelteon 8 mg, tablets, orally, once as daily clinical practice were observed for up to 4 weeks. A follow up of 2 weeks was carried out.
Measure Participants	2788
Sleep onset	69.6 2.2%
Sleep time	63.8 2%
Sleep quality	64.8 2%
Morning awakening	54.0 1.7%
Morning tiredness	52.9 1.6%
Daytime sleepiness	51.9 1.6%
Daytime physical condition/function	55.8 1.7%

Adverse Events

Time Frame	Baseline up to 6 weeks
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 collected in this study.
Arm/Group Title	Ramelteon
Arm/Group Description	Ramelteon 8 mg, tablets, orally, once as daily clinical practice were observed for up to 4 weeks. A follow up of 2 weeks was carried out.
All Cause Mortality
	Ramelteon
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ramelteon
	Affected / at Risk (%)	# Events
Total	1/3223 (0%)
General disorders
Death	1/3223 (0%)
Other (Not Including Serious) Adverse Events
	Ramelteon
	Affected / at Risk (%)	# Events
Total	37/3223 (1.1%)
Nervous system disorders
Somnolence	37/3223 (1.1%)

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.