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    The EU Clinical Trials Register currently displays   37554   clinical trials with a EudraCT protocol, of which   6160   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2004-004350-91
    Sponsor's Protocol Code Number:TAK-375/EC301
    National Competent Authority:Austria - BASG
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2005-11-24
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedAustria - BASG
    A.2EudraCT number2004-004350-91
    A.3Full title of the trial
    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
    A.4.1Sponsor's protocol code numberTAK-375/EC301
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorTakeda Global R&D Centre (Europe)
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Information not present in EudraCT
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameramelteon
    D.3.2Product code TAK-375
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeTAK-375
    D.3.10 Strength
    D.3.10.1Concentration unit % percent
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number90- to 110
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product Information not present in EudraCT
    D.3.11.8Extractive medicinal product Information not present in EudraCT
    D.3.11.9Recombinant medicinal product Information not present in EudraCT
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D.3.11.13.1Other medicinal product typesmall molecule melatonin agonist
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Information not present in EudraCT
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namezopiclone
    D.3.4Pharmaceutical form Capsule*
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNZopiclone
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number7.5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product Information not present in EudraCT
    D.3.11.8Extractive medicinal product Information not present in EudraCT
    D.3.11.9Recombinant medicinal product Information not present in EudraCT
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D.3.11.13.1Other medicinal product typesmall molecule sedative
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCapsule*
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    chronic insomnia
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 8
    E.1.2Level LLT
    E.1.2Classification code 10053851
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of this study is to evaluate the near maximum 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.
    E.2.2Secondary objectives of the trial
    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 and withdrawal effect 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.
    E.2.3Trial contains a sub-study Information not present in EudraCT
    E.3Principal 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.

    * Based on sleep history, the subject uses pharmacological assistance to sleep 0 to 4 times per week in the last 3 months. Subject must agree to discontinue use of all pharmacological sleep aids beginning one week prior to the dose of single-blind study medication and throughout the entire duration of the study.
    E.4Principal 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 paraoxysmal positional vertigo (BPPV).

    • The subject has ever had a history of seizures; sleep apnoea, COPD, Restless Leg Syndrome (RLS), Periodic Leg Movement Syndrome (PLMS), 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.

    * The subject has participated in a weight loss program or has substantially altered their exercise routine witihin 30 days prior to the first night of single-blind study medication.

    * The subject intends to continue taking any disallowed medication or any prescription medication, over-the-counter (OTC) or herbal 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, OTC or herbal medications taken in the 3 weeks prior to screening.

    * The subject has any clinically important abnormal finding as determined by a medical history, physical examination, ECG, or clinical laboratory tests, as determined by the investigator. European responsible medical officer must approve subjects with clinically significant abnormal laboratory values being considered for the study with Takeda Europe R&D Centre Ltd and the Principal Investigator.
    E.5 End points
    E.5.1Primary end point(s)
    The primary variable for this study is the calculated area of centre of pressure (COP) recorded on the balance platform.

    The secondary variables for this study will include the efficacy varaiables mean LPS, subjective sleep latency (sSL), sbjective total sleep time (sTST), number of awakenings, sWASO, subjective quality sleep, restorative nature of sleep, morning alertness and ability to concentrate; the residual pharmacological effect variables digit symbol substitution test (DSST) and memory recall tests; the sleep architecture variables percentage of total sleep time in REM sleep, Stage 1, 2 and 3, 4 NREM sleep and latency of REM as determined by PSG screening, as well as subject's ability to stand on balance platform Night 14.

    The safety variables for this study will include adverse events, laboratory tests, vital signs and physical examination findings.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Information not present in EudraCT
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    with reference arm
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    double dummy
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    zopiclone vs placebo
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.5The trial involves multiple Member States Yes
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    E.8.7Trial has a data monitoring committee Information not present in EudraCT
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    14 nights of single blind placebo medication with 28 nights of double blind treatment
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months2
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Information not present in EudraCT
    F.2.2Male Information not present in EudraCT
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Information not present in EudraCT
    F.3.3.1Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2005-11-24. Yes
    F.3.3.2Women of child-bearing potential using contraception Information not present in EudraCT
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state18
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 184
    F.4.2.2In the whole clinical trial 275
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2005-12-29
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2005-12-29
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2006-09-25
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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