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

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

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.

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.

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.