insomnia characterised by difficulty with sleep onset MedDRA version: 9.1 Level: LLT Classification code 10053851 Term: Chronic insomnia
Conditions
Interventions
Product Name: Ramelteon
Product Code: TAK-375
Pharmaceutical Form: Tablet
INN or Proposed INN: Ramelteon
Current Sponsor code: TAK-375
Sponsors
Takeda Global Research & Development Centre (Europe) Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The subject is male or female aged 18 to 64 years, inclusive. 2. A female subject of childbearing potential who is sexually active agrees to use adequate contraception from Screening throughout the duration of the study. Women NOT of childbearing potential are defined as those who have been surgically sterilized (hysterectomy, oophorectomy, tubal ligation) or who are postmenopausal (defined as at least 2 years since last regular menses). Acceptable methods of contraception are defined in Section 9.1.15 Contraception and Pregnancy Avoidance Procedure. 3. Female subjects must have negative serum pregnancy test result at the screening visit (Visit1) and a negative urine pregnancy test result on the evening of the PSG screening visit (Visit 3). 4. The subject is capable of understanding and complying with protocol requirements and only those subjects that have fully understood and signed the informed consent document at screening, prior to any study related procedures being performed, will be enrolled into the study. 5. The subject or the subject’s legally acceptable representative signs a written informed consent form prior to the initiation of any study procedures. 6. The subject has a body mass index between 18 and 34, inclusive. 7. Based on sleep history, the subject has had chronic insomnia for at least 3 months, as defined by the following: (a) The predominant complaint is difficulty initiating or maintaining sleep, or nonrestorative sleep, for at least 3 months. (b) The sleep disturbance (or associated daytime fatigue) causes clinically significant distress or impairment in social, occupational, or other important areas of functioning. (c) The sleep disturbance does not occur exclusively during the course of narcolepsy, breathing-related sleep disorder, circadian rhythm sleep disorder, or parasomnia. (d) The disturbance does not occur exclusively during the course of another mental disorder (eg, major depressive disorder, generalized anxiety disorder, delirium). (e) 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. 8. Based on sleep history, the subject reports a history of subjective sleep latency (sSL) =45 minutes and a subjective total sleep time (sTST) =6.5 hours, for at least 3 months. 9. Based on sleep history, the subject’s habitual bedtime is between 10:00 PM and 1:00 AM. 10. On at least 3 of the first 5 nights of single-blind run-in placebo treatment, the subject must have an sSL of =45 minutes and an sTST of <6.5 hours. Note: The sSL and sTST inclusion criteria are not required to be met on the same nights. 11. The difference of the average sSL from first 3 nights of data in the first week of single-blind run-in (eg, Nights -21 to -19) to the average of the last 3 nights of data in the first week of single-blind run-in (eg, nights -17 to -15) must be = 30 minutes. 12. The difference of the average sSL from first 3 nights of data in the first week of single-blind run-in (eg, Nights -21 to -19) to the average of the last 3 nights of data in the second week of single-blind run-in (eg, nights -10 to -8) must be = 30 minutes. 13. The difference of
Exclusion criteria
Exclusion criteria: 1. The subject has a known hypersensitivity to ramelteon or related compounds, including melatonin. 2. The subject has participated in a study involving ramelteon within 6 months of initial Screening Visit. 3. The subject has participated in any other investigational study and/or taken any investigational drug within 30 days or 5 half-lives (whichever is longer) prior to the first night of single-blind study medication. 4. The subject has sleep schedule changes required by employment (eg, shift worker) within 3 months prior to the first night of single-blind study medication, or has flown across greater than 3 time zones within 7 days prior to screening. 5. The subject has participated in a weight loss program or has substantially altered his or her exercise routine within 30 days prior to the first night of single-blind study medication. 6. The subject has ever had a history of seizures; sleep apnea, restless leg syndrome, periodic leg movements during sleep (PLMS), chronic obstructive pulmonary disease, fibromyalgia, schizophrenia, bipolar disorder, mental retardation, cognitive disorder or a positive test result for the aforementioned ailments on the screening PSG. 7. The subject has a history of psychiatric disorder within the past 12 months. 8. The subject has a history of drug addiction or drug abuse within the past 12 months. 9. The subject has a history of alcohol abuse within the past 12 months. 10. The subject has a current significant neurological (including cognitive and psychiatric disorders), hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, hematological, or metabolic disease, unless currently controlled and stable with protocol-allowed medication 30 days prior to the first night of single blind study medication. 11. The subject uses tobacco products (including nicotine gum and patch) during nightly awakenings. 12. The subject has used any central nervous system medication, 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. These medications must not have been used to treat psychiatric disorders. 13. The subject intends to continue taking any disallowed medication or any prescription medication or over-the counter (OTC) medication that is known to affect the sleep/wake function or otherwise interfere with evaluation of the study medication. The subject must report all prescription and OTC medications taken in the 3 weeks prior to Screening. 14. The subject has any clinically important abnormal finding as determined by a medical history, physical examination, electrocardiogram, or clinical laboratory tests, as determined by the investigator. NOTE: Subjects with clinically significant abnormal laboratory values being considered for the study must be approved by both the sponsor and the principal investigator. 15. The subject has a history of hepatitis B or C. 16. The subject has a positive urine drug screen for an illegal substance at the initial Screening Visit. NOTE: Subjects with positive urine drug screen for legal substances, including alcohol, at initial screening, whe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: The secondary objective of this study is to evaluate the safety (including next-morning residual effects, rebound and withdrawal) and other sleep parameters of ramelteon 4 mg compared to placebo in subjects with chronic insomnia.;Main Objective: To evaluate the efficacy of ramelteon 4 mg compared to placebo in subjects with chronic insomnia.; Primary end point(s): The primary efficacy variable will be the mean latency to persistent sleep (LPS) via PSG, over Nights 1 and 2 of double-blind treatment. The secondary efficacy variables will be mean LPS via PSG over Nights 15 and 16, and over Nights 29 and 30. Additional secondary efficacy variables will be total sleep time (TST), sleep efficiency, wake time after persistent sleep, number of awakenings after persistent sleep as determined by PSG. Subjective assessment of treatment outcomes will be captured using PSQ-IVRS, sSL, sTST, subjective sleep quality, subjective awake time, subjective number of awakenings, and subjective ease of falling back to sleep as determined by PSQ/sleep diary. Additional parameters will be recorded using the digit symbol substitution test, memory recall test, and visual analog scale. Measures of LPS will be used to assess rebound insomnia upon single-blind placebo run-out period. The subjective morning alertness and ability to concentrate will be captured via PSQ. The Tyrer Benzodiazepine Withdrawal Symptom Questionnaire will be used to assess subjective effects of withdrawal from study medication. Sleep architecture variables include percentage of TST in rapid eye moment (REM) sleep, stage 1, 2 and 3/4 nonrapid eye movement sleep, and latency to REM as determined by PSG. Safety variables will include adverse events, laboratory tests, vital signs, electrocardiogram results, and physical exam findings. | — |
Countries
Austria, Finland, France, Germany, United Kingdom
Outcome results
None listed