Clinical trial NCT00631657: A 6-Month Efficacy and Safety Study of Org 50081 in Adult Patients With Chronic Primary Insomnia (21106/P05701/MK-8265-002)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Sleep Initiation and Maintenance Disorders
Mental Disorders
Dyssomnias
Sleep Disorders
Sleep Disorder, Intrinsic
Keywords: placebo controlled
randomized
double blind
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2008-03-10
Enrollment: 460
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change From Baseline in Total Sleep Time (TST) - 6-Month Treatment Period
timeFrame: Baseline and the Mean of Weeks 14-26
Secondary outcomes:
measure: Number of Participants Who Experienced Adverse Events (AEs)
timeFrame: Up to 31 weeks
measure: Number of Participants Who Discontinued Study Drug Due to an AE
timeFrame: Up to 27 weeks
measure: Change From Baseline in Sleep Latency (SL) - 6-Month Treatment Period
timeFrame: Baseline and the Mean of Weeks 14-26
measure: Change From Baseline in Wake Time After Sleep Onset (WASO) - 6-Month Treatment Period
timeFrame: Baseline and the Mean of Weeks 14-26
Other outcomes:
measure: Change From Baseline in Number of Awakenings (NAW) - 6-Month Treatment Period
timeFrame: Baseline and the Mean of Weeks 14-26
measure: Change From Baseline in Sleep Quality - 6-Month Treatment Period
timeFrame: Baseline and the Mean of Weeks 14-26
measure: Change From Baseline in Satisfaction With Sleep Duration - 6-Month Treatment Period
timeFrame: Baseline and the Mean of Weeks 14-26
measure: Change From Baseline in Two Aggregate Measures of Short Form 36 (SF-36) Health Survey Score - 6-Month Treatment Period
timeFrame: Baseline and Week 26
measure: Change From Baseline in Investigator Global Rating (IGR) - 6-Month Treatment Period
timeFrame: Baseline and Week 26
measure: Change From Baseline in Investigator Global Rating (IGR) - 7-Day Discontinuation Period
timeFrame: Baseline and End of 7-day Discontinuation Period
Locations:
Study officials:
References:
citation: Ivgy-May N, Hajak G, van Osta G, Braat S, Chang Q, Roth T. Efficacy and safety of esmirtazapine in adult outpatients with chronic primary insomnia: a randomized, double-blind placebo-controlled study and open-label extension. J Clin Sleep Med. 2020 Sep 15;16(9):1455-1467. doi: 10.5664/jcsm.8526.