Efficacy and Safety Study of Org 50081 (Esmirtazapine) in Elderly Participants (P05709)

Insomnia is a common complaint or disorder throughout the

world. About one third of the population in the industrial

countries reports difficulty initiating or maintaining sleep,

resulting in a non-refreshing or non-restorative sleep. The

majority of the insomniacs suffer chronically from their

complaints.

The maleic acid salt of Org 4420, code name Org 50081, known as Esmirtazapine, was

selected for development in the treatment of insomnia. The

first clinical trial with Esmirtazapine was a proof-of-concept trial

with a four-way cross-over design. All 3 Esmirtazapine dose

groups showed a statistically significant positive effect on

TST (objective and subjective) and WASO, as compared to

placebo.

The current study is designed to assess the efficacy and safety

of Esmirtazapine in a double-blind, placebo-controlled, parallel,

randomized trial in elderly participants suffering from chronic

primary insomnia.

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;