Trial Outcomes & Findings for 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 - (NCT NCT02153086)

NCT ID: NCT02153086

Last Updated: 2016-10-13

Results Overview

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.

• Recruitment status: COMPLETED
• Target enrollment: 236 participants
• Primary outcome timeframe: Baseline up to 12 months
• Results posted on: 2016-10-13

Participant Flow

Participants took part in the study at 2 investigative sites in Japan from 01 March 2011 to 30 June 2014.

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).

Participant milestones

Measure	Ramelteon 8 mg 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 Study STARTED	236
Overall Study COMPLETED	232
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Measure	Ramelteon 8 mg 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 Study Not enrolled >=28 days and <=56 days	2
Overall Study Other	2

Baseline Characteristics

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 -

Baseline characteristics by cohort

Measure	Ramelteon 8 mg n=232 Participants 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.
Age, Continuous	65.1 years STANDARD_DEVIATION 18.6 • n=5 Participants
Sex: Female, Male Female	139 Participants n=5 Participants
Sex: Female, Male Male	93 Participants n=5 Participants
Type of sleep disorders (Major symptoms) Difficulty falling asleep	127 participants n=5 Participants
Type of sleep disorders (Major symptoms) Difficulty getting sound sleep	16 participants n=5 Participants
Type of sleep disorders (Major symptoms) Difficulty staying asleep	44 participants n=5 Participants
Type of sleep disorders (Major symptoms) Early morning awakening	2 participants n=5 Participants
Type of sleep disorders (Major symptoms) Unknown	43 participants n=5 Participants
Degree of sleep disorders Mild	72 participants n=5 Participants
Degree of sleep disorders Moderate	130 participants n=5 Participants
Degree of sleep disorders Severe	30 participants n=5 Participants
Duration of insomnia Less than (<) 1 year	102 participants 2.71 • n=5 Participants
Duration of insomnia Greater than equal to (>=) 1 year to <3 years	15 participants n=5 Participants
Duration of insomnia >=3 to <5 years	14 participants n=5 Participants
Duration of insomnia >=5 years	11 participants n=5 Participants
Duration of insomnia Unknown	90 participants n=5 Participants
Presence of complications Had Complications	193 participants n=5 Participants
Presence of complications Had No Complications	39 participants n=5 Participants
Breakdown of complications Hypertension	86 participants n=5 Participants
Breakdown of complications Dyslipidaemia	57 participants n=5 Participants
Breakdown of complications Mental disease	32 participants n=5 Participants
Breakdown of complications Allergic disease	23 participants n=5 Participants
Breakdown of complications Diabetes mellitus	22 participants n=5 Participants
Breakdown of complications Heart or cerebrovascular disease	22 participants n=5 Participants
Breakdown of complications Renal and urinary disorders	17 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to 12 months

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

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.

Outcome measures

Measure	Ramelteon 8 mg n=232 Participants 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.
Number of Participants Reporting One or More Adverse Drug Reactions	0 participants

SECONDARY outcome

Timeframe: Baseline, Week 4 and Month 12

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. The data was assessed at baseline, Week 4 and final visit (last visit for a participant in the study, up to Month 12).

Outcome measures

Measure	Ramelteon 8 mg n=207 Participants 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.
Sleep Status: Sleep Onset Latency Baseline (n=143)	98.7 minutes Standard Deviation 73.3
Sleep Status: Sleep Onset Latency At Week 4 (n=109)	48.3 minutes Standard Deviation 57.6
Sleep Status: Sleep Onset Latency At Final Assessment (n=127)	38.9 minutes Standard Deviation 39.4

SECONDARY outcome

Timeframe: Baseline, Week 4 and Month 12

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. The data was assessed at baseline, Week 4 and final visit (last visit for a participant in the study, up to Month 12).

Outcome measures

Measure	Ramelteon 8 mg n=207 Participants 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.
Sleep Status: Total Sleep Time Baseline (n=137)	6.74 hours Standard Deviation 2.11
Sleep Status: Total Sleep Time At Week 4 (n=102)	7.51 hours Standard Deviation 1.64
Sleep Status: Total Sleep Time At Final Assessment (n=120)	7.46 hours Standard Deviation 1.72

SECONDARY outcome

Timeframe: Baseline, Week 4 and Month 12

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. The data was assessed at baseline, Week 4 and final visit (last visit for a participant in the study, up to Month 12).

Outcome measures

Measure	Ramelteon 8 mg n=207 Participants 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.
Sleep Status: Number of Awakenings Baseline (n=150)	2.3 number of awakenings Standard Deviation 1.5
Sleep Status: Number of Awakenings At Week 4 (n=115)	1.2 number of awakenings Standard Deviation 1.2
Sleep Status: Number of Awakenings At Final Assessment (n=136)	1.1 number of awakenings Standard Deviation 1.1

SECONDARY outcome

Timeframe: At Week 4, 52, and final assessment (up to 12 months)

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 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).

Outcome measures

Measure	Ramelteon 8 mg n=207 Participants 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.
Percentage of Participants Reported With Improvement on the Patient Global Impression (PGI) Scale for Sleep Onset At Week 4 (n=207)	80.2 percentage of participants 1.5
Percentage of Participants Reported With Improvement on the Patient Global Impression (PGI) Scale for Sleep Onset At Week 52 (n=88)	93.2 percentage of participants 1.2
Percentage of Participants Reported With Improvement on the Patient Global Impression (PGI) Scale for Sleep Onset At Final Assessment (n=207)	85.5 percentage of participants 1.1

SECONDARY outcome

Timeframe: At Week 4, 52, and final assessment (up to 12 months)

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 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).

Outcome measures

Measure	Ramelteon 8 mg n=207 Participants 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.
Percentage of Participants Reported With Improvement on the PGI Scale for Sleep Duration At Week 4 (n=207)	77.8 percentage of participants 1.5
Percentage of Participants Reported With Improvement on the PGI Scale for Sleep Duration At Week 52 (n=88)	93.2 percentage of participants 1.2
Percentage of Participants Reported With Improvement on the PGI Scale for Sleep Duration At Final Assessment (n=207)	84.0 percentage of participants 1.1

SECONDARY outcome

Timeframe: At Week 4, 52, and final assessment (up to 12 months)

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 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).

Outcome measures

Measure	Ramelteon 8 mg n=207 Participants 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.
Percentage of Participants Reported With Improvement on the PGI Scale for Sleep Quality At Week 4 (n=207)	80.2 percentage of participants 1.5
Percentage of Participants Reported With Improvement on the PGI Scale for Sleep Quality At Week 52 (n=88)	93.2 percentage of participants 1.2
Percentage of Participants Reported With Improvement on the PGI Scale for Sleep Quality At Final Assessment (n=207)	86.0 percentage of participants 1.1

SECONDARY outcome

Timeframe: At Week 4, 52, and final assessment (up to 12 months)

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

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).

Outcome measures

Measure	Ramelteon 8 mg n=207 Participants 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.
Percentage of Participants Reported With Improvement on the PGI Scale for Morning Awakening At Week 4 (n=207)	67.6 percentage of participants 1.5
Percentage of Participants Reported With Improvement on the PGI Scale for Morning Awakening At Week 52 (n=88)	87.5 percentage of participants 1.2
Percentage of Participants Reported With Improvement on the PGI Scale for Morning Awakening At Final Assessment (n=207)	77.8 percentage of participants 1.1

SECONDARY outcome

Timeframe: At Week 4, 52, and final assessment (up to 12 months)

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

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).

Outcome measures

Measure	Ramelteon 8 mg n=207 Participants 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.
Percentage of Participants Reported With Improvement on the PGI Scale for Remaining Tiredness in the Morning At Week 4 (n=207)	72.5 percentage of participants 1.5
Percentage of Participants Reported With Improvement on the PGI Scale for Remaining Tiredness in the Morning At Week 52 (n=88)	81.8 percentage of participants 1.2
Percentage of Participants Reported With Improvement on the PGI Scale for Remaining Tiredness in the Morning At Final Assessment (n=207)	77.3 percentage of participants 1.1

SECONDARY outcome

Timeframe: At Week 4, 52, and final assessment (up to 12 months)

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

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).

Outcome measures

Measure	Ramelteon 8 mg n=207 Participants 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.
Percentage of Participants Reported With Improvement on the PGI Scale for Daytime Somnolence At Week 4 (n=207)	65.2 percentage of participants 1.5
Percentage of Participants Reported With Improvement on the PGI Scale for Daytime Somnolence At Week 52 (n=88)	81.8 percentage of participants 1.2
Percentage of Participants Reported With Improvement on the PGI Scale for Daytime Somnolence At Final Assessment (n=207)	76.8 percentage of participants 1.1

SECONDARY outcome

Timeframe: At Week 4, 52, and final assessment (up to 12 months)

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

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).

Outcome measures

Measure	Ramelteon 8 mg n=207 Participants 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.
Percentage of Participants Reported With Improvement on the PGI Scale for Daytime Physical Condition/Function At Week 4 (n=207)	70.5 percentage of participants 1.5
Percentage of Participants Reported With Improvement on the PGI Scale for Daytime Physical Condition/Function At Week 52 (n=88)	84.1 percentage of participants 1.2
Percentage of Participants Reported With Improvement on the PGI Scale for Daytime Physical Condition/Function At Final Assessment (n=207)	77.3 percentage of participants 1.1

Adverse Events

Ramelteon 8 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: trialdisclosures@takeda.com

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