Trial Outcomes & Findings for Ramelteon Tablets 8mg Drug Use Surveillance: Survey on Insomnia Associated With Sleep-onset Difficulty (NCT NCT02058992)

NCT ID: NCT02058992

Last Updated: 2016-07-14

Results Overview

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.

Recruitment status

COMPLETED

Target enrollment

3339 participants

Primary outcome timeframe

Baseline up to 6 weeks

Results posted on

2016-07-14

Participant Flow

Participants took part in the study at 557 investigative site in Japan from 30 July 2010 to 30 April 2013.

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).

Participant milestones

Participant milestones
Measure	Ramelteon 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 Study STARTED	3339
Overall Study COMPLETED	3223
Overall Study NOT COMPLETED	116

Reasons for withdrawal

Reasons for withdrawal
Measure	Ramelteon 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 Study Lost to Follow-up	4
Overall Study Protocol Violation	92
Overall Study CRF Uncollected	20

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ramelteon n=3223 Participants 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.
Age, Continuous	63.5 years STANDARD_DEVIATION 18.9 • n=5 Participants
Age, Customized Less than (<) 65 years	1379 participants n=5 Participants
Age, Customized Greater than or equal to (>=)65 years to <75 years	733 participants n=5 Participants
Age, Customized >=75 years	1111 participants n=5 Participants
Sex: Female, Male Female	1935 Participants n=5 Participants
Sex: Female, Male Male	1288 Participants n=5 Participants
Type of Sleep Disorder (Major Symptoms) Difficulty falling asleep	1966 participants n=5 Participants
Type of Sleep Disorder (Major Symptoms) Difficulty getting sound sleep	302 participants n=5 Participants
Type of Sleep Disorder (Major Symptoms) Difficulty staying asleep	458 participants n=5 Participants
Type of Sleep Disorder (Major Symptoms) Early morning awakening	50 participants n=5 Participants
Type of Sleep Disorder (Major Symptoms) Unknown	447 participants n=5 Participants
Degree of Sleep Disorder Mild	1354 participants n=5 Participants
Degree of Sleep Disorder Moderate	1569 participants n=5 Participants
Degree of Sleep Disorder Severe	300 participants n=5 Participants
Duration of Insomnia	1.13 years STANDARD_DEVIATION 2.45 • n=5 Participants
Duration of Insomnia < 1 year	1522 participants n=5 Participants
Duration of Insomnia >=1 year to <3 years	241 participants n=5 Participants
Duration of Insomnia >=3 to < 5 years	107 participants n=5 Participants
Duration of Insomnia >=5 years	135 participants n=5 Participants
Duration of Insomnia Unknown	1218 participants n=5 Participants
Presence of Complications Had Complications	2618 participants n=5 Participants
Presence of Complications Had No Complications	605 participants n=5 Participants
Breakdown of complications Hypertension	1206 participants n=5 Participants
Breakdown of complications Dyslipidaemia	694 participants n=5 Participants
Breakdown of complications Mental disease	495 participants n=5 Participants
Breakdown of complications Diabetes mellitus	419 participants n=5 Participants
Breakdown of complications Heart or cerebrovascular disease	393 participants n=5 Participants
Breakdown of complications Renal and urinary disorders	158 participants n=5 Participants
Breakdown of complications Hepatobiliary disorders	133 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to 6 weeks

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

Outcome measures

Outcome measures
Measure	Ramelteon n=3223 Participants 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.
Number of Participants Reporting One or More Adverse Drug Reactions	109 participants

PRIMARY outcome

Timeframe: Baseline up to 6 weeks

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

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.

Outcome measures

Outcome measures
Measure	Ramelteon n=3223 Participants 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.
Number of Participants Reporting One or More Serious Adverse Drug Reactions	1 participants

SECONDARY outcome

Timeframe: Baseline and Week 4

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

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.

Outcome measures

Outcome measures
Measure	Ramelteon n=1429 Participants 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.
Sleep Status: Sleep Onset Latency Baseline	89.8 minutes Standard Deviation 66.7
Sleep Status: Sleep Onset Latency Week 4	47.1 minutes Standard Deviation 46.2

SECONDARY outcome

Timeframe: Baseline and Week 4

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

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

Outcome measures

Outcome measures
Measure	Ramelteon n=1292 Participants 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.
Sleep Status: Total Sleep Time Baseline	6.49 hours Standard Deviation 2.00
Sleep Status: Total Sleep Time Week 4	7.31 hours Standard Deviation 1.72

SECONDARY outcome

Timeframe: Baseline and Week 4

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

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.

Outcome measures

Outcome measures
Measure	Ramelteon n=1401 Participants 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.
Sleep Status: Number of Awakenings Baseline	2.1 number of awakenings Standard Deviation 1.6
Sleep Status: Number of Awakenings Week 4	1.2 number of awakenings Standard Deviation 1.2

SECONDARY outcome

Timeframe: Week 4

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

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.

Outcome measures

Outcome measures
Measure	Ramelteon n=2788 Participants 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.
Percentage of Participants Who Responded With Improvement on the Patient Global Impression (PGI) Scale at Week 4 Sleep onset	69.6 percentage of participants
Percentage of Participants Who Responded With Improvement on the Patient Global Impression (PGI) Scale at Week 4 Sleep time	63.8 percentage of participants
Percentage of Participants Who Responded With Improvement on the Patient Global Impression (PGI) Scale at Week 4 Sleep quality	64.8 percentage of participants
Percentage of Participants Who Responded With Improvement on the Patient Global Impression (PGI) Scale at Week 4 Morning awakening	54.0 percentage of participants
Percentage of Participants Who Responded With Improvement on the Patient Global Impression (PGI) Scale at Week 4 Morning tiredness	52.9 percentage of participants
Percentage of Participants Who Responded With Improvement on the Patient Global Impression (PGI) Scale at Week 4 Daytime sleepiness	51.9 percentage of participants
Percentage of Participants Who Responded With Improvement on the Patient Global Impression (PGI) Scale at Week 4 Daytime physical condition/function	55.8 percentage of participants

Adverse Events

Ramelteon

Serious events: 1 serious events

Other events: 37 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ramelteon n=3223 participants at risk 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.
General disorders Death	0.03% 1/3223 • Baseline up to 6 weeks 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.

Other adverse events

Other adverse events
Measure	Ramelteon n=3223 participants at risk 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.
Nervous system disorders Somnolence	1.1% 37/3223 • Baseline up to 6 weeks 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.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER