A Non-inferiority Study With Two Treatment Arms Eszopiclone 3 mg Versus Zopiclone 7.5 mg - for the Treatment of Insomnia

A Phase III, Non-inferiority, Double-blind, Unicenter Clinical Trial With Two Treatment Arms - Test Group With Eszopiclone 3 mg Versus Zopiclone 7.5 mg - for the Treatment of Insomnia

The primary objective of the study is to determine whether eszopiclone (Eurofarma) is non-inferior to the reference drug zopiclone (Imovane®, Sanofi-Aventis) in the treatment of insomnia.

The primary objective of the study is to determine whether eszopiclone (Eurofarma) is non-inferior to the reference drug zopiclone (Imovane®, Sanofi-Aventis) in the treatment of insomnia. To that end, the latency to persistent sleep (LPS) will be used as a primary endpoint at the end of the treatment, measured by polysomnography.

The secondary objectives and endpoints of this study are as follows:

• To evaluate the efficiency of eszopiclone compared to zopiclone by means of the patient's clinical history, using as secondary endpoints:
• Variables of the sleep diary of the Associação Fundo de Incentivo à Psicofarmacologia (see Appendix A), namely:
• Latency time to the beginning of the sleep;
• Frequency of night wake-ups;
• Time awake during bedtime;
• Early morning awakening;
• Total time in bed;
• Sleep efficiency;
• Sleep variables measured by actigraph;
• Insomnia Severity Index (see Appendix B);45
• Pittsburgh Sleep Quality Index (see Appendix C);46
• To evaluate the safety of eszopiclone compared to zopiclone by means of adverse events in each study arm.

Inclusion Criteria:

• Sign the informed consent form for the study;
• Be ≥ 20 to ≥ 64 years old;
• Have diagnosis of symptomatic primary insomnia for at least 3 months;
• Have polysomnography conducted at least 90 days before the inclusion in the study with sleep time less than 6.5 hours and sleep latency ≥ 20 minutes;
• Be able not to take any insomnia medication for 14 days before randomization to the study (washout period).

Exclusion Criteria:

• Diagnosis of other sleep disorder by polysomnography conducted 90 days before the inclusion in the study;
• Use of any medication affecting the sleep, such as psychotropic, hypnotic or antihistamine agents for at least 15 days before the inclusion in the study;
• Use of any herbal supplement for insomnia or melatonin during the 14 days before entering the study;
• Current use of liver metabolized medication, especially those metabolized through the cytochrome P450 enzyme complex, especially through the CYP3A4 and/or CYP2E1 routes;
• History of daily use of alcohol beverages in quantities equivalent - from the ethanol standpoint - to two cans of beer a day (35 g of alcohol/day);
• History of substance abuse or dependence;
• Patients with severe co-morbidities (at the investigator's opinion);
• Presence of liver disorders, cirrhosis or liver failure;
• Presence of psychiatric disorders diagnosed at the adult life or currently under treatment;
• Pregnant and breastfeeding women and women who want to become pregnant during the study period and who refuse to use a proper contraceptive methods during the study.