A 6-Month Efficacy and Safety Study of Org 50081 in Adult Patients With Chronic Primary Insomnia (21106/P05701/MK-8265-002)

Study Overview
=================
Brief Summary
-----------------
To investigate the long-term efficacy and safety of treatment with esmirtazapine (Org 50081, SCH 900265, MK-8265) compared to placebo, in participants with chronic primary insomnia. Primary efficacy variable is Total Sleep Time (TST).

Detailed Description
-----------------
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 (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 Wake Time After Sleep Onset (WASO), as compared to placebo. The current study is designed to assess the long-term efficacy and safety of esmirtazapine in a double-blind, randomized, placebo-controlled, parallel group outpatient trial in participants suffering from chronic primary insomnia. During the 6-month treatment period, participants are randomly assigned to receive either esmirtazapine or placebo. Then, during the 7-day discontinuation period, participants who received esmirtazapine in the 6-month treatment period are randomly assigned to receive either esmirtazapine or placebo, while participants who received placebo in the 6-month treatment period continue to receive placebo.

Official Title
-----------------
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

Conditions
-----------------
Sleep Initiation and Maintenance Disorders, Mental Disorders, Dyssomnias, Sleep Disorders, Sleep Disorder, Intrinsic

Intervention / Treatment
-----------------
* Drug: Esmirtazapine
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: are at least 18 and less than 65 years; sign written informed consent after the scope and nature of the investigation have been explained; have shown capability to complete the LogPad questionnaires; have difficulty falling asleep, maintaining sleep or have early morning awakening; Exclusion Criteria: Significant medical or psychiatric illness causing sleep disturbances. Have a history of bipolar disorder or attempted suicide or have a family (immediate family) history of suicide. Have a sleep disorder such as sleep-related breathing disorder, restless leg syndrome, narcolepsy. Significant other medical illness such as acute or chronic pain, heart-, kidney-, or liver disease within the last year. Currently diagnosed or meet the criteria for Major Depressive Disorder (MDD) or have been treated for MDD in the last 2 years. Substance abuse, excessive use of alcohol (determined by the physician) or drug addiction within the last year. Are night workers or rotating shift workers or plan to travel through more than 3 time-zones. Routinely nap during the day. Have a Body Mass Index (BMI) of 36 or more.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Esmirtazapine 4.5 mg<br>Participants receive esmirtazapine 4.5 mg tablets, administered once a day for 6 months | Drug: Esmirtazapine<br>* One esmirtazapine 4.5 mg tablet once a day<br>|
| Placebo Comparator: Placebo<br>Participants receive placebo tablets, administered once a day for 6 months | Drug: Placebo<br>* One placebo tablet once a day<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Sleep Time (TST) - 6-Month Treatment Period | TST was defined as the time recorded for sleep diary question 6 How much time did you actually spend sleeping? as reported by participants using a LogPad (hand-held electronic data capture device). Baseline was defined as the mean TST from the Placebo Run-in Period. Change from Baseline was calculated as the mean of combined data from Weeks 14 through 26, using a last observation carried forward (LOCF) approach. | Baseline and the Mean of Weeks 14-26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experienced Adverse Events (AEs) | An AE is defined as any unfavorable and unintended change in the structure, function or chemistry of the body whether or not considered related to study drug. The number of participants who experienced AEs is combined for the 6-Month Treatment Period and the 7-Day Discontinuation Period. | Up to 31 weeks | 
| Number of Participants Who Discontinued Study Drug Due to an AE | An AE is defined as any unfavorable and unintended change in the structure, function or chemistry of the body whether or not considered related to study drug. The number of participants who discontinued study drug due to an AE is combined for the 6-Month Treatment Period and the 7-Day Discontinuation Period. | Up to 27 weeks | 
| Change From Baseline in Sleep Latency (SL) - 6-Month Treatment Period | SL was defined as the time recorded for sleep diary question 3 How long did it take you to fall asllep?, as reported by participants using a LogPad. Baseline was defined as the mean SL from the Placebo Run-in Period. Change from Baseline was calculated as the mean of combined data from Weeks 14 through 26, using an LOCF approach. | Baseline and the Mean of Weeks 14-26 | 
| Change From Baseline in Wake Time After Sleep Onset (WASO) - 6-Month Treatment Period | WASO was defined as the time recorded for sleep diary question 5 How much time were you awake, after falling asleep initially?, as reported by participants using a LogPad. Baseline was defined as the mean WASO from the Placebo Run-in Period. Change from Baseline was calculated as the mean of combined data from Weeks 14 through 26, using an LOCF approach. | Baseline and the Mean of Weeks 14-26 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
randomized, placebo controlled, double blind