Almorexant in Primary Insomnia

Study Overview
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Brief Summary
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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.

Official Title
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Multi-center, Multiple-stage, Double-blind, Randomized, Placebo-controlled, Two-way Crossover, Single-dose Study to Investigate the Effects of ACT-078573 on Sleep Measured by Polysomnography in Patients With Primary Insomnia

Conditions
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Insomnia, Primary Insomnia

Intervention / Treatment
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* Drug: almorexant
* Drug: almorexant
* Drug: almorexant
* Drug: almorexant
* Drug: almorexant


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: almorexant<br>* 1 dose of 400 mg in two treatment sequences<br>* Other names: ACT-078573;|
| Experimental: 2<br> | Drug: almorexant<br>* 1 dose of 200 mg in two treatment sequences<br>* Other names: ACT-078573;|
| Experimental: 3<br> | Drug: almorexant<br>* 1 dose of 100 mg in two treatment sequences<br>* Other names: ACT-078573;|
| Experimental: 4<br> | Drug: almorexant<br>* 1 dose of 50 mg mg in two treatment sequences<br>* Other names: ACT-078573;|
| Experimental: 5<br> | Drug: almorexant<br>* 1 dose of 1000 mg in two treatment sequences<br>* Other names: ACT-078573;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sleep efficiency (%) assessed by PSG (polysomnography) |  | Between 10pm-12am (=lights out) until 480 minutes thereafter (=lights on) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LPS (Latency to Persistent Sleep) [min] assessed by PSG (polysomnography) |  | Time from start of recording to the beginning of the first continuous 20 epochs of non-wake |