A multicentre, randomised, double-blind, double-dummy, placebo-controlled study to evaluate the safety and efficacy of ramelteon compared to placebo with zopiclone as a reference arm in adults with chronic insomnia

INTERVENTION: Product Name: ramelteon Product Code: TAK‐375 Pharmaceutical Form: Tablet Current Sponsor code: TAK‐375 Concentration unit: % percent Concentration type: range Concentration number: 90‐110 Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use Trade Name: zimovane Product Name: zopiclone Pharmaceutical Form: Tablet Pharmaceutical form of the placebo: Capsule* Route of administration of the placebo: Oral use CONDITION: chronic insomnia ; MedDRA version: 8 Level: LLT Classification code 10053851 INCLUSION CRITERIA: General • The subject is a male or female 18 to 64 years of age, inclusive. • The subject is capable of understanding and willing to comply with the protocol and has signed the informed consent document at screening prior to any study related procedures being performed. Study‐specific • The subject, if female, is non‐pregnant and non‐lactating. Females of childbearing potential must use appropriate birth control (barrier methods, hormonal contraceptives, and/or intrauterine devices) for the entire duration of the study. Females who are not of childbearing potential must be postmenopausal for 1 year or have a history of hysterectomy and/or bilateral oophorectomy. • Based on sleep history, the subject has had chronic insomnia as defined by the following: • A complaint is difficulty initiating or maintaining sleep or of nonrestorative sleeps that lasts for at least 3 months. • The sleep disturbance (or associated daytime fat PRIMARY OUTCOME: Main Objective: The primary objective of this study is to evaluate the near peak effect of ramelteon 8mg once daily based on balance/postural sway versus placebo with zopiclone 7.5mg as a reference arm in subjects with chronic insomnia with subject’s eyes open. Primary end point(s): The primary safety endpoint is the balance/postural stability as calculated by the area of centre of pressure (COP) recorded by the balance platform (AccuSway approximately 1.5 hours post‐dose during Night 14. This will be assessed using the change from pre‐dose to post‐dose in COP on Night 14 of the double blind treatment.; Secondary endpoint will be to assess the effects of Ramelteon on psychomotor and cognitive performance approximately 1.5 hours post‐dose during Night 14 using scores from the DSST and memory recall tests. ; Additional secondary endpoints will assess the efficacy of Ramelteon by using the mean LPS and TST per PSG, over nights 1/ 2 and 27/ 28, sSL, sTST, number of awakenings, sWASO, subjective quality of sleep, restorative nature of sleep , morning alertness and the ability to concentrate from the post‐sleep questionnaire over nights 1/2 and 27/28, sleep architecture variables include percentage of total sleep time in rapid eye movement (REM) sleep, Stage 1, 2 and 3, 4 non rapid eye movement (NREM) sleep and latency to REM as determined by PSG in the double‐blind treatment.; Safety variables will include adverse events, laboratory tests, vital signs, ECG results, and physical exam findings.; Secondary Objective: To evaluate the treatment effect of ramelteon 8mg once daily in reduction of objective and subjective latency to persistent sleep (LPS) and changes in balance postural sway with eyes closed compared to placebo with Zopiclone 7.5mg as a reference arm in subjects with chronic insomnia.; ; To evaluate the residual pharmacological effect, sleep architecture of ramelteon 8mg once daily compare to placebo with Zopiclone 7.5mg as a reference arm in subjects with chronic insomnia.; ; To evaluate the safety of ramelteon in insomniac population.; ; Third objective(s):; The third objective of this study is to evaluate daytime function activities.