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    The EU Clinical Trials Register currently displays   32439   clinical trials with a EudraCT protocol, of which   5226   are clinical trials conducted with subjects less than 18 years old.
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    EudraCT Number:2006-004025-28
    Sponsor's Protocol Code Number:HTA 05-14-02
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2007-05-16
    Trial results
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    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2006-004025-28
    A.3Full title of the trial
    MENDS: The use of MElatonin in children with Neuro-developmental Disorders and impaired Sleep; a randomised, double-blind, placebo-controlled, parallel study
    A.3.2Name or abbreviated title of the trial where available
    A.4.1Sponsor's protocol code numberHTA 05-14-02
    A.5.1ISRCTN (International Standard Randomised Controlled Trial) Number5534585
    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 SponsorRoyal Liverpool Children’s NHS Trust
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing support
    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 No
    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 nameMelatonin
    D.3.2Product code APL-510
    D.3.4Pharmaceutical form Capsule, hard
    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 INNmelatonin
    D.3.9.2Current sponsor codeAPL-510
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number0.5, 2.0 to 6.0, 12.0
    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. cell therapy medicinal product No
    D. therapy medical product No
    D. Engineered Product Information not present in EudraCT
    D. ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D. 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 No
    D.3.11.8Extractive medicinal product No
    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 No
    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 placeboCapsule, hard
    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
    children with neuro-developmental disorders and impaired sleep
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level PT
    E.1.2Classification code 10064062
    E.1.2Term Neurodevelopmental disorder
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level PT
    E.1.2Classification code 10040984
    E.1.2Term Sleep disorder
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The objective of this trial is to confirm (or refute) that immediate release melatonin is beneficial when compared to placebo in improving total duration of night-time sleep and in reducing sleep latency (the time taken to fall asleep) in children with neuro-developmental problems.

    At randomisation, each patient will be allocated their own ‘individual patient package’ containing either melatonin or placebo. Each child will be given the first dose and kept on that dose for a minimum of seven days. For the next three weeks and at each one-week interval during this time, the child’s sleep disorder will be reviewed (using subjective and objective) and the medication either left unchanged or increased to the next dose increment. There are a maximum of 3 dose increments after the starting dose of 0.5 mg, through 2, 6 and up to a maximum of 12 mg. Each child will remain on whichever dose is felt to have been the most effective.
    E.2.2Secondary objectives of the trial
    Total night time sleep calculated using actigraphy data
    Sleep efficiency calculated from the actigraphy
    Composite sleep disturbance index scores
    Daily global measure of parental perception of child’s sleep quality
    Behavioural problems assessed using Aberrant Behaviour Checklist
    Quality of Life of the care-giver assessed using the Family Impact Module of the PedsQL
    Level of daytime sleepiness of caregiver assessed using the Epworth Sleepiness Scale
    Number and severity of seizures evaluated using seizure diaries throughout trial follow-up
    Adverse effects of melatonin treatment assessed weekly between weeks T0W to T12W using ‘TESS’ (Treatment Emergent Signs and Symptoms)
    Salivary melatonin concentrations
    Associations between genetic variants and abnormal melatonin production
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    “Processes in Recruitment to Randomised Controlled Trials (RCT’s) of medicines for children (RECRUIT)”. RECRUIT was approved in its own right by the North West MREC at its meeting on 2 March 2007 (REF 07/MRE08/6).
    RECRUIT will be examining communication processes in the recruitment of participants to MENDS with the aim of identifying strategies for subsequent trials of medicines for children to improve trial recruitment and conduct. RECRUIT will involve:
    a) Routine audio-recording of MENDS discussions (consultations) between families and practitioners (trial recruiters).
    b) Follow-up interviews with up to 8 families (parents and children where aged 7 or over) who agree to participate in MENDS.
    c) Follow-up interviews with up to 8 families (parents and children where aged 7 or over) who decline participation in MENDS.
    d) Follow-up interviews with up to 8 trial recruiters involved in approaching families to take part in MENDS.
    If permission for audio-recording is declined by a family the recruitment consultation will not be recorded. If permission is given the recruiter will activate an audio-recorder. At the end of the MENDS recruitment consultation the recruiter will discuss RECRUIT with the family and seek their permission to pass their details to one of the RAs employed on RECRUIT, who will then make contact with families and obtain written informed consent for participation in the RECRUIT study. Recordings from families who decline RECRUIT will be erased as soon as practicable. All families who express an interest in RECRUIT but are not selected for follow-up interview will be contacted by letter to thank them and inform them that their recordings have been erased. Audio-recordings of the recruitment consultations will only be released to the RECRUIT RAs after the consent of participants has been obtained.
    E.3Principal inclusion criteria
    1. Children aged 3 years to 15 years 8 months at screening.
    2. Diagnosis of a neuro-developmental disorder that has been made by a community paediatrician, paediatric neurologist or paediatric neurodisability consultant, categorised as:
    a. developmental delay alone
    b. developmental delay and epilepsy*
    c. developmental delay and autistic spectrum disorder* (ASD)
    d. developmental delay with ‘other’ (‘other’ is defined as the child having a specific genetic/chromosomal disorder).
    or any combination of the above.
    3. Adaptive Behaviour Assessment System (ABAS) questionnaire score with a percentile rank below 7.
    4. Minimum 5 months history of impaired sleep at screening as defined by:
    a. not falling asleep within one hour of 'lights off' or 'snuggling down to sleep' at age-appropriate times for the child**, and/or:
    b. less than 6 hours of continuous sleep in three nights out of five
    5. Children whose parents are likely to be able to use the actigraph and complete sleep diaries
    6. Children who are able to comply with taking the study drug
    7. English speaking
    8. Children whose parents have completed sleep diaries for an average of 5 out of 7 nights at T0W.

    * In coding the presence of epilepsy and ASD diagnoses, we will require sight of documentation from relevant services that demonstrate appropriate diagnostic assessments and investigations have been used
    ** This will be the child’s usual bedtime (recorded in the sleep diary) based upon the family’s normal routine
    E.4Principal exclusion criteria
    1. Children treated with melatonin within 5 months prior to screening
    2. Any plans to commence the following medication:
    • any benzodiazepines
    • amisulpride (Solian)
    • chlorpromazine (Largactil)
    • haloperidol (Haldol)
    • olanzapine (Zyprexa)
    • risperidone (Risperdal)
    • sertindole (Serdolect)
    • sulpiride (Sulpidil, Sulpor)
    • thioridazine (Melleril)
    • trifluoperazine (Stelazine)
    3. Current use of beta blockers (minimum of 7 days washout required)
    4. Current use of sedative or hypnotic drugs, including Choral hydrate, Triclofos and alimemazine tartrate (Vallergan) (minimum of 14 days washout required)
    5. Children with a known allergy to melatonin
    6. Regular consumption of alcohol (> 3 times per week)
    7. Children for whom there are suggestive symptoms of Obstructive Sleep Apnoea Syndrome (OSAS) (such as combinations of snoring, gasping, excessive sweating or stopping breathing during sleep), physical signs supportive of OSAS (such as very large tonsils/very small chin), or results of investigations suggesting OSAS (such as overnight pulse oximetry or polysomnography) for which the child should be referred to appropriate respiratory or ENT colleagues for specific assessment and treatment
    8. Girls or young women who are pregnant at the time of screening (T– 4W)
    9. Currently participating in a conflicting clinical study or participation in a clinical study involving a medicinal product within the last 3 months
    E.5 End points
    E.5.1Primary end point(s)
    1. Total duration of night-time sleep.
    2. Sleep onset latency (the time taken to fall asleep).
    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 Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    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 No
    E. trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    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 No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    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.8.4.1Number of sites anticipated in Member State concerned12
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.7Trial has a data monitoring committee Yes
    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
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months9
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months9
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    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) Yes
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    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 2007-05-16. Yes
    F.3.3.2Women of child-bearing potential using contraception Yes
    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 Yes
    F. of subjects incapable of giving consent
    children <16 years
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state172
    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 Decision2007-06-26
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2007-05-26
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2011-04-04
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