Efficacy and Safety of Circadin® 2 mg in the Treatment of Primary Insomnia Patients

Study Overview
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Brief Summary
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This is a randomised, placebo controlled study to evaluate the efficacy of a 3 week treatment period with Circadin® 2 mg in shortening sleep latency in patients with primary insomnia aged 18-80 with melatonin deficiency.

Detailed Description
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Studies throughout the world have shown that insomnia is a common complaint that occurs in 10-50% of the population depending on age, sex and country. Among the wide variety of available treatments of sleep disturbances, the most commonly prescribed hypnotics are the benzodiazepines (BZD) and non-BZD hypnotics. However, these hypnotics were often associated with rebound, dependency, tolerance, higher risk of falls mainly in the elderly population, anterograde memory disturbances and increased risk for motor accidents the next day. In response to the unmet clinical need for a safe and efficacious alternative treatment for primary insomnia, that in addition to treating quantitative sleep problems, would improve sleep quality and daytime functioning, a clinical development program on melatonin for the treatment of primary insomnia was initiated. This study is conducted using a randomised, double-blind, placebo controlled parallel group design, after a single-blind placebo period. Primary insomnia patients aged 18-80 will be screened for entry into the study. After the initial 3 weeks double-blind treatment period, patients will be given the option to enter a six-month double-blind continuation study. Primary parameter is sleep latency, secondary parameter is sleep maintenance. Exploratory parameters are total sleep time, sleep quality, morning alertness and quality of life.

Official Title
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A Double-blind, Parallel Group, Randomised, Placebo Controlled Study of Efficacy and Safety of Circadin® 2 mg in the Treatment of Insomnia Patients With Low Endogenous Melatonin

Conditions
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Primary Insomnia

Intervention / Treatment
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* Drug: Circadin
* Drug: placebo circadin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female and aged 18-80 years. Are willing to take a 6-SMT level evaluation test. Suffering from primary insomnia according to DSM-IV. criteria (307.42 primary insomnia, Appendix 24.3) . Sleep latency of at least 20 minutes. Have not been using benzodiazepines (BZD) and non-BZD hypnotics for the past 2 weeks or more. Have not been using psychotropic treatments for the past 3 months or more. Are stabilized on non-psychotropic treatments for more than 1 month. Are willing to sign a written informed consent to participate in the study. Exclusion Criteria: Use of benzodiazepines or other hypnotics (including psychotropic treatments) during the study and preceding two weeks. Alcohol intake more than 30 g of pure alcohol per day and any intake after lunch-time. Pharmacological immunosuppression. Participation in a clinical trial with any investigational agent within two months prior to study enrollment. According to DSM IV, subjects belonging to the following groups are excluded: 780.59 (breathing related sleep disorder); 307.45 (circadian rhythm sleep disorder); 307.47 (dyssomnia not otherwise specified); 780.xx (sleep disorder due to general medical condition). Severe neurological, psychiatric disorders (especially psychosis, anxiety and depression) and alcoholism. Other serious diseases that could interfere with patient assessment. Pregnant or breast feeding women.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Circadin<br> | Drug: Circadin<br>* Prolonged release melatonin 2 mg<br>* Other names: ATC code: N05CH01;|
| Placebo Comparator: placebo<br> | Drug: placebo circadin<br>* placebo circadin tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Change From Baseline in Subjective Sleep Latency. | Sleep latency (SL) after 3 weeks of treatment was assessed by Patient Daily Sleep Diary (National sleep foundation sleep diary). The patients reported subjectively of their SL. The Sleep Diary question 3 (SL) was summarised at baseline (end of the two-week run-in period) and after three weeks double-blind treatment (actual and change from baseline) for each treatment group using descriptive statistics. At each visit, the mean of the seven days prior to the visit were used. For each treatment group, the mean score at visit 3 was compared, adjusting for the visit 2 score. An ANCOVA model was used. Lower score indicates reduction in sleep latency and thus considered improvement | Baseline and 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Change From Baseline in Subjective Sleep Maintenance. | Sleep maintenance as measured by number of awakening (NOA) after 3 weeks of treatment was assessed by Patient Daily Sleep Diary (National sleep foundation sleep diary). The patients reported subjectively of their NOA. The Sleep Diary question 4 (NOA) was summarized at baseline (end of the two-week run-in period) and after three weeks double-blind treatment (actual and change from baseline) for each treatment group using descriptive statistics. At each visit, the mean of the seven days prior to the visit were used. For each treatment group, the mean score at visit 3 was compared, adjusting for the visit 2 score. An ANCOVA model was used. Lower score indicates less awakenings and thus considered improvement. | 3 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary insomnia as defined by DSM IV criteria