Almorexant in Primary Insomnia

Inclusion Criteria:

• Men or women 18 - 65 years of age (inclusive).
• Women of childbearing potential must have a negative urine pregnancy test at the screening visit, the screening adaptation night, and pre-treatment and use a reliable method of contraception during the entire study duration and for at least 3 months after study drug intake.

Reliable methods of contraception are:

• Barrier type devices (e.g., female condom, diaphragm, contraceptive sponge) only in combination with a spermicide.
• Intra-uterine devices.

• Oral, injectable, implantable or transdermal contraceptives only in combination with a barrier method.

  • Abstention, rhythm method, and contraception by the partner alone are not acceptable methods of contraception.

Women not of childbearing potential are defined as prepubescent, postmenopausal (i.e., amenorrhea for at least 1 year), or surgically or naturally sterile.

• Body mass index (BMI) between 18 and 30 kg/m2 (limits included) at screening visit.
• 12-lead ECG without clinically relevant abnormalities at screening visit.
• Hematology and biochemistry test results not deviating from the normal range to a clinically relevant extent at screening visit and following the screening/adaptation night.
• Primary insomnia by DSM-IV-TR criteria based on medical history and the assessments performed at screening visit.

• History of the following for at least 3 months prior to the screening visit:

  • Usual reported subjective total sleep time (TST) 3 - 6 hours.
  • Usual sleep disturbance with a subjective sleep onset latency of > 30 min.
  • Daytime complaints associated with poor sleep (e.g., fatigue, irritability, difficulty concentrating).
• Polysomnography (PSG) at screening/adaptation night confirming TST < 6 h and LPS ≥ 20 min.
• Willingness to refrain from CNS-active drugs for 5 half-lives of the respective drug (but at least 1 week) prior to the screening/adaptation night and up to the end of treatment period 2. The usage of short-acting hypnotics (defined as hypnotics with a half-life of up to and including 10 hours) is allowed up to 48 hours prior to each PSG night, i.e., prior to the screening/adaptation night and prior to the treatment PSG nights.
• Urine drug test negative for barbiturates, cannabinoids, amphetamines, and cocaine at screening visit 1, screening/adaptation PSG night and pre-treatment. Urine drug test negative for benzodiazepines and opiates at screening/adaptation PSG night and pre-treatment.
• Signed informed consent prior to any study-mandated procedure.

Exclusion Criteria:

• Symptom assessment questionnaire (SBB) for diagnosis of apnea resulting in a score > 2 at screening visit.
• Zung self-rating depression scale (SDS) and/or Zung self-rating anxiety scale (SAS) resulting in a raw score ≥ 50 at screening visit.
• Restless legs syndrome and/or meeting all four essential diagnostic criteria for RLS (see Appendix 10).

• Insomnia due to sleep apnea or periodic limb movement disorder as assessed by PSG at screening/adaptation night:

  • apnea/hypopnea index (AHI) > 10/h
  • periodic limb movement arousal index > 10/h
• Major depressive disorder, severe psychosis, or significant anxiety disorder.
• Pregnancy or breast-feeding.
• Systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg at screening visit.
• Within the 2-month period prior to the screening visit, clinical evidence of alcoholism or drug abuse.
• Any known factor or disease that might interfere with treatment compliance, study conduct or interpretation of the results such as psychiatric disease or a disease which may affect the pharmacokinetics of the study drug.
• Treatment with strong inhibitors of CYP3A4 (e.g., azole derivatives, ritonavir, clarithromycin) within 1 week prior to the screening/adaptation PSG night and up to the end of treatment period 2.
• Excessive caffeine consumption (regular caffeine consumption of > 7 units per day).
• Night shift workers.
• Known hypersensitivity to any excipients of the drug formulation.
• Planned treatment or treatment with another investigational drug within 1 month prior to randomization and up to the end of treatment period 2.
• Known concomitant life-threatening disease with a life expectancy < 24 months.
• Unstable medical abnormality, significant medical disorder or acute illness.
• Recruitment of the same patient twice to the same dose level. Patients may be recruited to a lower dose level, provided that there are at least 28 days between last study drug administration and screening/adaptation PSG night.