NCT00325728.

Methods	RCT Stratified by severity of dementia (mild AD (MMSE 19 to 28) or moderate AD (MMSE 8 to 18))
Participants	Number of participants: 74 randomised, 66 completed study Country: USA (38 sites) Diagnosis: diagnosis of dementia of the Alzheimer's type (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised), or probable AD (NINCDS‐ADRDA criteria) Sleep‐related inclusion criteria: History of 2 or more sleep disorder behaviours occurring at least once weekly in the 2 weeks prior to the first screening visit and actigraphy evidence of a night‐time total sleep time < 7 h/night, based on at least 4/7 nights of complete actigraphy data collected over the single‐blind, placebo run‐in period Gender: 32 women, 42 men Age: mean age 76 years (minimum for inclusion 55 years) Severity of dementia: mild or moderate, defined as MMSE of 8 to 28, inclusive
Interventions	Ramelteon (Rozerem) 8 mg once a day at bedtime, or placebo
Outcomes	Actigraphic data collected at 1, 2, 4, 6, and 8 weeks Primary outcome: Mean nTST as determined by actigraphy (further specified in trial synopsis as nTST at 1 week) Secondary outcomes: night‐time wake time after sleep onset number of night‐time awakenings daytime total sleep time ratio of daytime to night‐time sleep number of daytime naps sleep efficiency safety and tolerability via AEs, laboratory tests, physical examinations, vital signs, and ECGs Exploratory: NPI MMSE CGGI ADCS‐ADL SDI CAS CGI
Notes	Phase 2 study of efficacy, safety and tolerability. Study completed in 2007. Sponsor: Takeda Global Research & Development Center, Inc. No peer reviewed publications identified
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"This was a double‐blind, randomized, placebo‐controlled, parallel‐group, proof‐of‐concept study." No further information provided. 43/74 (58%) participants received placebo
Allocation concealment (selection bias)	Unclear risk	No information available
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	"This was a double‐blind, randomized, placebo‐controlled, parallel‐group, proof‐of‐concept study." No further information provided
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	"This was a double‐blind, randomized, placebo‐controlled, parallel‐group, proof‐of‐concept study." No further information provided
Incomplete outcome data (attrition bias) All outcomes	Low risk	8/74) participants (10.8%) discontinued prematurely (4 placebo, 4 ramelteon 8 mg). Of these, 5 participants withdrew due to an AE (3 placebo, 2 ramelteon). 2 participants withdrew voluntarily, and 1 participant was terminated for other reasons. ITT and per protocol analyses conducted
Selective reporting (reporting bias)	Low risk	Although reporting of results in the clinical trial synopsis was cursory, mention was made of all planned outcomes
Other bias	Unclear risk	No information available