Phase IV 3-Way Double-blind, Randomized, Crossover Study to Compare the Awakening Threshold Effects (responsivity) of Belsomra 10 mg and 20 mg to Placebo in non-elderly Insomniacs

The study is an interventional single site study using a double blind, randomized 3-way crossover design with Belsomra 10 mg and 20 mg compared to a placebo. The total number of enrolled patients proposed is 12. A cross-over design is utilized so participants will be exposed to all treatment conditions in a controlled order (Belsomra 10 mg, 20 mg and placebo). Both men and women with insomnia will be utilized as the study population to improve the generalizability of outcome data. Subjects with other sleep disorders or unstable medical/psychiatric disorders will be excluded from the trial. Inclusion criteria will be men and women >18 and < 65 years of age.

Subjects will be randomly assigned to treatment sequences using a Latin square design. After a subject has qualified for the study, the next sequentially available randomization number will be assigned. The subject will be administered study drug corresponding with this assigned number.

During the night of each respective Polysomnography (PSG) assessments, subjects will be awoken at the approximate T-max of the active drug (2.5 hrs), with a matching placebo condition at the same time point using an identical responsivity protocol for each condition. The rationale for this is that t-max represents the time of greatest potential risk for a hypnotic in terms of balance, responsivity, and memory. Responsivity will be assessed using the Auditory Awakening Threshold test (AAT) and will be measured at 2.5 hours post dose for the Belsomra 10 and 20 mg (BEL), and placebo (PBO) conditions. Responsivity will be assessed at the approximate time above immediately after 5 minutes of consolidated (without arousals) NREM ( Non- rapid eye movement) stage 2 sleep has occurred.

Inclusion Criteria

• Meets DSM-5 ( Diagnostic and statistical manual) diagnostic criteria for insomnia disorder
• ISI ( Insomnia Severity Index) > 10
• Age >18 and < 65
• Negative audiological screening exam

Exclusion Criteria:

• BMI >35 kg/m2
• Have symptoms consistent with the diagnosis of any sleep disorder other than insomnia (e.g., sleep apnea, narcolepsy, periodic leg movements, or restless leg syndrome).
• Have a known or suspected diagnosis of Acquired Immune Deficiency Syndrome (AIDS), or have tested seropositive for human immunodeficiency virus (HIV) antibody or antigen previously.
• Have any clinically significant abnormal finding in physical examination, neurological assessment, vital signs, elevated body temperature, or clinical laboratory tests, as determined by the Investigator.
• Have a known or exaggerated pharmacological sensitivity, hypersensitivity, or intolerance to Belsomra.
• Currently taking CYP3A inhibitors.
• Positive breathalyzer test for alcohol at Screening, PSG Screening or any Treatment night, or a positive urine drug screen (for amphetamines, barbiturates, benzodiazepines, cocaine, opiates, or cannabinoids) at Screening;
• History of hearing difficulty (e.g., use of a hearing aid).
• Intends to use any medication including over-the-counter (OTC) medications that would interfere with normal sleep architecture (such as systemic steroids, beta-adrenergic blockers, amphetamines, modafinil, etc.);
• Self-reports use of products containing nicotine of greater than 15 cigarettes daily, or cannot avoid products containing nicotine during the normal sleep periods;
• Self report consumption of more than five alcoholic beverages on any one day or > 14 alcoholic beverages weekly over the past week;
• Have a history of epilepsy or serious head injury
• Average Time in Bed < 6.5 hrs.
• Have used prescribed or OTC medications within 7 days of screening (Day 0) or intend to use any prescription or OTC medication during the study that may interfere with the evaluation of the study drug. This restriction includes taking medications that affect the Central nervous system. Any chronic maintenance therapy should have been maintained at a stable dosing regimen for at least 30 days before screening and subjects must continue this regimen throughout the study.
• Have used an investigational drug within 30 days or five half lives (whichever is longer) before screening, or plans to use an investigational drug during the study or have used belsomra or zolpidem

2 weeks

Adverse Event were collected before and after every overnight. In addition, a Safety Follow-up 2 weeks after either study completion or study withdrawal was performed.

Study is double blinded. Investigator, participant, or care provider will be blinded to watch drug the subject receives during each treatment week.