Almorexant in Primary Insomnia

The aim of the study is to determine the minimum effective dose of ACT-078573 on sleep efficiency and to assess the effects of different doses of ACT-078573 on other PSG parameters.


Eligibility Criteria:
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.