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    Summary
    EudraCT Number:2007-005236-92
    Sponsor's Protocol Code Number:21106
    National Competent Authority:Hungary - National Institute of Pharmacy
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2007-12-29
    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 ConcernedHungary - National Institute of Pharmacy
    A.2EudraCT number2007-005236-92
    A.3Full title of the trial
    A 6-month, double-blind, randomized, placebo-controlled, parallel group outpatient trial, investigating the efficacy and safety of Org 50081 in adult patients with chronic primary insomnia.
    A.3.2Name or abbreviated title of the trial where available
    AQUAMARINE
    A.4.1Sponsor's protocol code number21106
    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 SponsorNV Organon
    B.1.3.4CountryNetherlands
    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 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 nameOrg 50081
    D.3.2Product code Org 50081
    D.3.4Pharmaceutical form Film-coated 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.3.8INN - Proposed INNesmirtazapine
    D.3.9.1CAS number 680993-85-5
    D.3.9.2Current sponsor codeOrg 50081
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number4.5
    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 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 Yes
    D.3.11.13.1Other medicinal product typea medicinal product with an active substance of chemical origin
    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 placeboFilm-coated tablet
    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
    Primary insomnia
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10036701
    E.1.2Term Primary insomnia
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    • To demonstrate the long-term efficacy of treatment with Org 50081, as compared to placebo, on sleep maintenance in patients with chronic primary insomnia as measured by the subjective Total Sleep Time. Primary efficacy endpoint is the average of subjective Total Sleep Time (TST) during month 4 to month 6, as recorded daily in the sleep diary.
    E.2.2Secondary objectives of the trial
    • To demonstrate the long-term efficacy of Org 50081 in improving sleep latency (SL),
    • To investigate the long term efficacy of Org 50081 on other sleep maintenance parameters WASO, NAW
    and on sleep quality and satisfaction with sleep duration.
    • To investigate the long-term safety and tolerability of Org 50081, as compared to placebo.
    • To investigate the effects of discontinuation of Org 50081 after long-term treatment.
    • To explore the effect of Org 50081 on functional and quality of life outcomes as compared to placebo.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Subjects are eligible to participate in the trial, if they:
    1. are at least 18 and less than 65 years of age;
    2. sign written informed consent after the scope and nature of the investigation have been explained to them, before screening evaluations;
    3. are able to speak, read and understand the language of the investigator, study staff (including raters) and the informed consent form, and possess the ability to respond to questions, follow instructions and complete questionnaires;
    4. have demonstrated capability to independently complete the LogPad questionnaires and have completed the daily morning questionnaires at least 6 out of 7 days in the week preceding randomization;
    5. have a documented diagnosis of chronic primary insomnia, defined as fulfillment of the DSM-IV-TR criteria for primary insomnia (DSM-IV-TR 307.42) with a duration of ≥ 1 month;
    6. Fulfill the following criteria based on medical history. Each of these criteria should be present for at least 3 nights per week for at least one month;
    TST ≤ 6.5 hours
    WASO ≥ 60 minutes
    SL ≥ 30 minutes
    7. Normal bedtime should be within the 21:00 hours – 01:00 hour range, with no more variation than 2 hours for 5 nights out of 7.
    E.4Principal exclusion criteria
    Potential participants will be excluded if they:
    8. have other sleep disorders (DSM-IV-TR) e.g. rapid eye movement (REM) behavioral disorders, sleep related breathing disorders, periodic leg movement disorder, restless leg syndrome, narcolepsy, circadian sleep wake rhythm disorders, or any parasomnia;
    9. have any significant medical or DSM-IV-TR psychiatric illness causing the sleep disturbances;
    10. currently meet diagnostic criteria for DSM-IV-TR depression (MDD) or have been diagnosed and treated for MDD within the last 2 years;
    11. have a history of bipolar disorder, a history of suicide attempt or family history of suicide. A family history of suicide is defined as any history of suicide in the first and second degree family (parents, siblings, grandparents, or offspring), or a pattern of completed suicides (more than one) in the third degree family (aunts, uncles, nieces, and nephews);
    12. are night workers or rotating shift workers;
    13. are traveling, or have plans to travel through more than 3 time zones, more than 2 times during the trial (from Screening onwards);
    14. are routinely sleeping during daytime (napping) for more than 60 minutes per day, 3 times/week;
    15. have a significant, unstable medical illness e.g. acute or chronic pain, hepatic, renal, metabolic or cardiac disease;
    16. have clinically relevant ECG abnormalities at screening, as judged by the investigator;
    17. have clinically relevant abnormal hematology, biochemistry or urinalysis values at screening, as judged by the investigator;
    18. have DSM-IV-TR substance abuse or addiction within the last year;
    19. drink more than 2 alcoholic drinks in a day. One drink is approximately equal to: 12 oz or 360 ml of beer (regular or light), or 4 oz or 120 ml of red or white wine, or 2 oz or 60 ml of desert wine (e.g. port, sherry), or 12 oz or 360 ml of wine cooler (regular or light), or 1 oz or 30 ml or spirits (80 to 100 proof, e.g. whiskey, vodka);
    20. had serious head injury or stroke within the past year, or a history of (non-febrile) seizures;
    21. use of psychotropic drugs affecting sleep within 2 weeks prior to baseline (fluoxetine: 5 weeks);
    22. use of concomitant medication affecting sleep (see Protocol Section 3.4, Concomitant medication);
    23. smoke > 15 cigarettes per day and/or can not abstain from smoking during the night;
    24. drink excessive amounts of caffeinated beverages (more than 500 mg caffeine per day);
    25. have a positive urine drug screen at screening;
    26. are pregnant, lactating or females of childbearing potential not practicing a reliable doublebarrier method of contraception as judged by the investigator;
    27. have a body mass index (BMI) ≥ 36;
    28. have a known hypersensitivity to mirtazapine or to any of the exipients;
    29. participated in another clinical trial within the last 30 days prior to screening;
    30. participated in another clinical trial using esmirtazapine (Org 50081).
    E.5 End points
    E.5.1Primary end point(s)
    The average of the subjective Total Sleep Time (TST, response to question #6) week scores from Week 14 up to and including Week 26 (LOCF) based on the daily sleep diary.
    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 No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    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.7.1.3.1Other trial type description
    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 Yes
    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 concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA27
    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 No
    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 months6
    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 months6
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    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 2007-12-29. 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 No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state32
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 252
    F.4.2.2In the whole clinical trial 440
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Subjects who have completed Trial 21106 and are willing to receive treatment with Org 50081 for the following 6 months, will be asked to participate in the long-term safety extension trial 176003. In this extension trial, subjects will receive open label treatment with 4.5 mg of Org 50081.
    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 Decision2008-03-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2008-03-12
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
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