Pharmacological Treatment of Insomnia in Palliative Care

The clinical trial is a randomized, double-blind, placebo controlled, parallel-group, multicenter trial investigating the short time effectiveness of zopiclone on self-reported sleep quality in patients with advanced cancer who use opioids and who report insomnia. Patients with advanced cancer who use opioids and who report insomnia are randomized to either a hypnotic, zopiclone (Arm A) or placebo (Arm B) for six nights. For this study zopiclone Actavis 3.75 mg, 5 mg and 7.5 mg (active comparator) and placebo are defined as Investigational Medicinal Products. The initial dose is zopiclone/placebo 3.75 mg/day. Evaluation of sleep quality is performed in the morning after night 2 and 4 with evaluation of sleep quality by using a numerical rating scale 0-10 with the question "Please circle the number that best describes how you feel now" 0= Best sleep, 10= Worst possible sleep.

Inclusion criteria

• Histologically verified malignant disease
• Presence of metastatic / disseminated disease
• Presence of insomnia syndrome defined as:

• Self-reported difficulty with initiating sleep (greater than 30 minutes to sleep onset) and/or difficulty maintaining sleep (greater than 30 minutes nocturnal waking time); and
• Sleep difficulty at least 3 nights per week; and
• Sleep difficulty that causes significant impairment of daytime functioning (The patient will be asked if sleep difficulty result in altered daytime function i.e. feeling tired, lack of energy)
• Able to comply with all study procedures
• Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to ICH GCP, and national/local regulations.

Exclusion criteria

• On-going treatment or previous treatment (within last 4 weeks) for more than consecutive 3 days with medications given for insomnia
• Adverse reactions to zopiclone
• History of substance abuse
• Concomitant use of rifampicin and erythromycin
• Any other contraindication listed on the summary of product characteristics of the investigated medicinal product:

• Myasthenia gravis
• An established diagnosis of Severe impairment of respiratory function
• An established diagnosis of Severe hepatic insufficiency.(Child-Pugh grade B or C)
• An established diagnosis of sleep apnea
• Known hypersensitivity to the drug or to any component in its formulation: Lactose monohydrate, Calcium hydrogen phosphate, Maize starch, Croscarmellose sodium, Magnesium stearate, Titanium dioxide (E 171), Hypromellose, Iron oxide yellow/Iron oxide red (E 172) and Macrogol
• Unfit for participation for any reason as judged by the investigator
• Pregnancy or lactation
• Women of reproductive age not willing or unable to employ an effective method of contraception (sterilization, using IUD or oral contraception)
• Scheduled surgery within the next week
• In the need of change in scheduled opioid dose at baseline (study visit 1)
• Scheduled intravenous administration of chemotherapy during the study period (from baseline to day 8) or intravenous administration of chemotherapy during the last week
• Change in corticosteroid dose last week before baseline or planned dose change in corticosteroid dose within 7 days from baseline