Efficacy and Safety Study of Org 50081 (Esmirtazapine) in Elderly Participants (P05709)
Condition: Insomnia; Sleep Initiation and Maintenance Disorders; Mental Disorders; Dyssomnias; Sleep Disorders
MeSH terms: Sleep Initiation and Maintenance Disorders; Sleep Wake Disorders; Dyssomnias; Mental Disorders
Intervention: Esmirtazapine; Placebo
Intervention description: one tablet daily; one tablet daily
Intervention MeSH terms: Mirtazapine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 538.0
Sex: All
Minimum age: 65 Years
Healthy volunteers: No
Keywords: elderly; randomized; placebo controlled

Summary:

      This study was conducted to investigate the efficacy of treatment with Org 50081
      (Esmirtazapine)

      compared to placebo in elderly participants with chronic primary

      insomnia. Primary efficacy variable is Wake time After Sleep

      Onset (WASO), averaged over all in-treatment time points

      and measured by polysomnography (PSG).
    

Eligibility criteria:

        Inclusion Criteria:

          -  are at least 65 years of age at screening;

          -  sign written informed consent after the scope and

        nature of the investigation have been explained to

        them, before screening evaluations;

          -  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;

          -  have demonstrated capability to independently

        complete the LogPad questionnaires and have

        completed the questionnaires at least 6 out of 7 days of

        the week preceding randomization;

          -  have a regular sleep pattern, meaning bedtime regularly

        occurs between 2100 hours and 2400 hours, with no more variation

        from these boundaries than 2 times/ week, with 5-8.5

        hours in bed;

          -  have a documented diagnosis of chronic primary

        insomnia, defined as fulfillment of the Diagnostic and Statistical Manual of Mental
        Disorders IV - Text Revision (DSM-IV-TR) criteria

        for primary insomnia (DSM-IV-TR 307.42) with a duration

        of >= 1 month; fulfill the following PSG criteria on the

        two screening/baseline PSG nights:

          -  average Total Sleep Time (TST) < 6.5 h (and each night greater than or

        equal to 3 h and < 7 h),

          -  average WASO greater than or equal to 45 minutes

        (and each night greater than or equal to 30 min),

          -  average Latency to Persistent Sleep (LPS) 15 min (and each night greater than or

        equal to 10 min).

        Exclusion Criteria:

          -  have other sleep disorders (DSM-IV-TR), such as sleep

        related breathing disorders Apnea-Hypopnea Index (AHI) greater than or equal

        to 15), Periodic Leg Movements with Arousals Index (PLMAI)

        greater than or equal to 10), restless leg syndrome,

        narcolepsy, circadian sleep wake rhythm disorders,

        Rapid Eye Movement (REM) behavioral disorder or any parasomnia;

          -  have any significant medical or DSM-IV-TR

        psychiatric illness causing the sleep disturbances;

          -  currently meet diagnostic criteria for DSM-IV-TR

        depression Major Depressive Disorder (MDD) or have been diagnosed and treated

        for MDD within the last 2 years;

          -  have a history of bipolar disorder, a history of suicide attempt or a 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);

          -  have a history or signs of dementia or other serious

        cognitive impairment, as defined by a score of less than

        26 on the Mini-Mental State Examination;

          -  have a significant, unstable medical illness e.g. acute or

        chronic pain, hepatic, renal, metabolic or cardiac

        disease;

          -  had serious head injury or stroke within the past year,

        or a history of (non-febrile) seizures;

          -  have clinically relevant electrocardiogram (ECG) abnormalities at

        screening, as judged by the investigator;

          -  have clinically relevant abnormal hematology or

        biochemistry values at screening, as judged by the

        investigator;

          -  have DSM-IV-TR substance abuse or DSM-IV-TR

        addiction within the last year;

          -  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);

          -  are routinely sleeping during daytime (napping) for more than 20 minutes per day, 3
             days or more per week;

          -  are night workers or rotating shift workers currently, or in the past 6 months

          -  use of psychotropic drugs affecting sleep within two weeks prior to randomization
             (fluoxetine: five weeks);

          -  use of concomitant medication affecting sleep (e.g. anxiolytics, sedatives,
             antidepressants, antipsychotics, centrally active sedating antihistamines, central
             nervous system (CNS)

        stimulants, alpha-2-antagonists, respiratory stimulants and decongestants);

          -  smoke > 15 cigarettes per day and/or can not abstain from smoking during the night;

          -  drink excessive amounts of caffeinated beverages/day (more than 500 mg caffeine per
             day);

          -  have a body mass index (BMI) >= 36;

          -  have a positive urine drug screen at screening or at baseline;

          -  have a known hypersensitivity to mirtazapine or to any of the excipients;