Merck 2008.

Methods	Randomised, double‐blind, controlled trial
Participants	460 participants Inclusion criteria: aged 18‐64 years; signed written informed consent after the scope and nature of the investigation had been explained; had shown capability to complete the LogPad questionnaires; had difficulty falling asleep, maintaining sleep or have early morning awakening Exclusion criteria: significant medical or psychiatric illness causing sleep disturbances; history of bipolar disorder or attempted suicide or have a family (immediate family) history of suicide; sleep disorder such as sleep‐related breathing disorder, restless leg syndrome, narcolepsy; significant other medical illness such as acute or chronic pain, or heart, kidney or liver disease within the last year; currently diagnosed or meet the criteria for MDD or have been treated for MDD in the last 2 years; substance abuse, excessive use of alcohol (determined by the physician) or drug addiction within the last year; night workers or rotating shift workers or plan to travel through more than 3 time zones; routinely nap during the day; body mass index ≥ 36.
Interventions	Intervention: esmirtazapine 4.5 mg once a day for 6 months Comparator: placebo tablets once a day for 6 months
Outcomes	Primary outcome Change from baseline in TST over 6‐months. TST was defined as the time recorded for sleep diary question 6 "How much time did you actually spend sleeping?" as reported by participants using a LogPad (hand‐held electronic data capture device). Baseline was defined as the mean TST from the placebo run‐in period. Change from baseline was calculated as the mean of combined data from weeks 14‐26, using LOCF approach. Secondary outcomes Number of participants who experienced AEs up to 31 weeks. AE defined as any unfavourable and unintended change in the structure, function or chemistry of the body whether or not considered related to study drug. Number of participants who experienced AEs was combined for 6‐month treatment period and the 7‐day discontinuation period. Number of participants who discontinued study drug due to an AE up to 27 weeks. An AE defined as any unfavourable and unintended change in the structure, function or chemistry of the body whether or not considered related to study drug. Number of participants who discontinued study drug due to an AE was combined for the 6‐month treatment period and the 7‐day discontinuation period. Change from baseline in SL in 6‐month treatment period (baseline and mean of weeks 14‐26). SL defined as the time recorded for sleep diary question 3 "How long did it take you to fall asleep?", as reported by participants using a LogPad. Baseline was defined as the mean SL from the placebo run‐in period. Change from baseline was calculated as the mean of combined data from weeks 14‐26, using an LOCF approach. Change from baseline in WASO in 6‐month treatment period (baseline and mean of weeks 14‐26). WASO defined as the time recorded for sleep diary question 5 "How much time were you awake, after falling asleep initially?", as reported by participants using a LogPad. Baseline was defined as the mean WASO from the placebo run‐in period. Change from baseline was calculated as the mean of combined data from weeks 14‐26, using an LOCF approach. Other outcome measures Change from baseline in NAW in 6‐month treatment period (baseline and mean of weeks 14‐26). NAW defined as the number of times recorded for sleep diary question 4a "How many times did you wake up during the night?", as reported by participants using a LogPad. Baseline was defined as the mean NAW from the placebo run‐in period. Change from baseline was calculated as the mean of combined data from weeks 14‐26, using an LOCF approach. Change From baseline in sleep quality in 6‐month treatment period (baseline and the mean of weeks 14‐26). Sleep quality assessed using a VAS in response to the sleep diary question 7 "Rate the quality of your sleep last night", as reported by participants using a LogPad. Responses could range from 0 = Very poor to 100 = Excellent, with a higher score indicating greater sleep quality. Baseline was defined as the mean sleep quality score from the placebo run‐in period. Change from baseline was calculated as the mean of combined data from weeks 14‐26, using an LOCF approach. Change from baseline in satisfaction with sleep duration in 6‐month treatment period (baseline and the mean of weeks 14‐26). Satisfaction with sleep duration was assessed using a VAS in response to the sleep diary question 8 "How satisfied are you about your sleep duration of last night?", as reported by participants using a LogPad. Responses could range from 0 = Very unsatisfied to 100 = Fully satisfied, with a higher score indicating great satisfaction with sleep duration. Baseline was defined as the mean satisfaction with sleep duration score from the placebo run‐in period. Change from baseline was calculated as the mean of combined data from weeks 14‐26, using an LOCF approach. Change from baseline in 2 aggregate measures of the SF‐36 Health Survey Score in 6‐month treatment period (baseline and week 26). SF‐36 is a participant‐rated questionnaire that consists of 8 scaled scores: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning and mental health, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0‐100 scale on the assumption that each of the 8 questions carries equal weight. The SF‐36 can be divided into 2 aggregate summary measures: the Physical Component Summary and the Mental Component Summary. Scores range from 0 to 100, with a lower score indicating more disability. Baseline was defined as the SF‐36 score assessed at randomisations. Change from baseline in IGR in 6‐month treatment period (baseline and week 26). The IGR is a clinician‐rated 7‐point scale used to assess the severity of illness. Severity is rated on a scale from 1 = Normal to 7 = Extremely severe. Baseline was defined as the last non‐missing value obtained during the placebo run‐in period. Change from baseline in IGR in 7‐day discontinuation period.
Notes	Data from NCT website only. Unable to find any publications or contact authors.