chronic insomnia MedDRA version: 8 Level: LLT Classification code 10053851
Conditions
Interventions
Product Name: ramelteon
Product Code: TAK-375
Pharmaceutical Form: Tablet
Current Sponsor code: TAK-375
Concentration unit: % percent
Sponsors
Takeda Europe R&D Centre Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
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 fatigue) causes clinically significant distress or impairment in social, occupational, or other important areas of functioning. • The disturbance does not occur exclusively during the course of Narcolepsy, Breathing-Related Sleep Disorder, Circadian Rhythm Sleep Disorder or a Parasomnia. • The subject’s sleep disturbance does not occur exclusively during the course of another mental disorder (eg, Major Depressive Disorder, Generalised Anxiety Disorder, a delirium). • The disturbance is not due to the direct physiological effects of a substance (eg, a drug of abuse, a medication) or a general medical condition. • Based on sleep history, the subjects reports history sSL greater than or equal to 45 minutes, and sTST less than or equal to 6.5 hours. • The subject has mean LPS of =20 minutes on two consecutive screening nights with neither night less than 15 minutes. • The subject’s habitual bedtime is between 10:00 p.m. and 1:00 a.m. • Subjects should be able to stand with eyes closed, arms at side and feet apart at hips width for at least one minute with out taking a step. • The subject has a body mass index (BMI) between 18 and 34, inclusive. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: General • Subjects with a history of psychiatric disorder, or alcohol / drug abuse within the last 12 months. • The subject uses tobacco products during nightly awakenings. • The subject has a known hypersensitivity to ramelteon, zopiclone or related compounds, including melatonin. • The subject has any additional condition(s) that in the Investigator’s opinion would: a) affect sleep/wake function, b) prohibit the subject from completing the study, or c) not be in the best interest of the subject. Study-specific • The subject has participated in any other investigational study and/or taken any investigational drug within 30 days or five half-lives prior to the first night of single-blind study medication, whichever is longer. • The subject has sleep schedule changes required by employment (e.g. shift worker) within three months prior to the first night of single-blind study medication, or has flown across greater than three time zones within seven days prior to screening. • Subject has a history of or currently has conditions that would affect balance such as orthostatic hypotension, dizziness, vertigo, or benign paroxysmal positional vertigo (BPPV). • The subject has ever had a history of seizures; sleep apnoea, COPD, RLS, PLMS, schizophrenia, bipolar disorder, mental retardation, cognitive disorder or fibromyalgia. • The subject has a history of psychiatric disorder (including anxiety, depression, mental retardation, cognitive disorder, bipolar illness and schizophrenia) within the past 6 months. • The subject has a history of drug addiction or drug abuse within the past 12 months. • The subject has a history of alcohol abuse within the past 12 months, as defined in DSM-IV-TR TM, or regularly consumes more than 14 alcoholic drinks per week, or consumed any alcoholic drinks within 24 hours of all PSG visits. • The subject has a current significant neurological (including cognitive and psychiatric disorders), hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, haematological, or metabolic disease, unless currently controlled and stable with protocol-allowed medication 30 days prior to the first night of single blind study medication. • The subject has used melatonin, or other drugs or supplements known to affect sleep/wake function within 1 week (or 5 half lives of the drug, whichever is longer) prior to the first day of single-blind study medication. • The subject has used any central nervous system medication within 1 week (or 5 half lives of the drug, whichever is longer) prior to the first day of single-blind study medication. • The subject has a positive urine drug screen including alcohol at screening or a positive breathalyser test at each check-in. • The subject has an apnoea hypopnoea index (per hour of sleep) >10 as seen on PSG, on the first night of the PSG screening. • The subject has periodic leg movement (PLM) with arousal index (per hour of sleep) >10 as seen on PSG, on the first night of PSG screening. • Subjects who have lower limb prosthetics.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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.; 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. ; 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 p | — |
Countries
Austria, Finland, Germany, Italy, United Kingdom
Outcome results
None listed