Combination pharmacotherapy for co-morbid insomnia and obstructive sleep apnea (COMISA)

Exclusion Criteria41

• Participants are excluded from the study if any of the following criteria apply:
• Medical Conditions
• Presence of an acutely active or currently uncontrolled/unstable medical condition
• Clinically significant cardiac disease (e.g., rhythm disturbances, coronary artery disease or cardiac failure)
• Clinically significant neurological disorder, including epilepsy/convulsions
• Clinically significant cognitive dysfunction
• Respiratory disorders other than sleep disordered breathing: chronic hypoventilation/hypoxemia (awake SaO2 < 92% by oximetry) due to chronic obstructive pulmonary disease or other respiratory conditions
• Conditions likely to affect obstructive sleep apnea physiology: heart failure, neuromuscular disease, uncontrolled hypertension or other major neurological disorder
• Diagnosed circadian or sleep disorders, excluding insomnia and OSA (e.g. delayed sleep phase disorder, periodic limb movements, narcolepsy, restless leg syndrome or parasomnias)
• Presence of schizophrenia, schizoaffective disorder, generalized anxiety disorder, PTSD acute unmanaged depression, or bipolar disorder according to Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5).
• Acute history of, or planned, circadian disruption (e.g. night or early morning shift work in the past year or trans meridian travel [>/= 2 time zones] in the past 2 months)
• A significant illness or infection requiring medical treatment in the past 30 days
• Allergies to sulfonamides (e.g. hydrochlorothiazide, furosemide, sulfasalazine, celecoxib, sumatriptan, and zonisamide)
• Adrenocortical insufficiency
• Electrolyte disturbance (hyponatremia, hypokalaemia, hypomagnesemia)
• Hyperchloremic acidosis
• Positive screen for drugs of abuse or history of substance use disorder as defined in DSM-V within 24 months prior to Screening Visit
• Long QT syndrome or a family history of Long QT syndrome
• Prolonged QT interval (>450 ms in men or >470 ms in women)
• Women who are pregnant, or planning pregnancy during the study period, or nursing
• Prior/Concomitant Therapy
• Current use of the medications under investigation to treat different conditions (sulthiame for epilepsy or trazodone for depression). For trazodone used as hypnotic, see 25
• Current use of acetazolamide or any other carbonic anhydrase inhibitor
• Current enrolment in a cognitive behavioural intervention for insomnia
• Current use of treatment for OSA or snoring – Participant may enrol as long as treatment is discontinued 5 days prior to commencement of trial procedures and continues to abstain for the duration of the trial
• Current use of devices to affect participant sleeping position for the treatment of OSA or snoring, e.g. to discourage supine sleeping position – Participant may enrol as long as treatment is discontinued 5 days prior to commencement of trial procedures and continues to abstain for the duration of the trial
• Use of medications expected to stimulate or depress respiration (including opioids, barbiturates, doxapram, almitrine, theophylline, 4-hydroxybutanoic acid)
• Current use of hypnotic medications (e.g. trazodone, eszopiclone, benzodiazepines) or melatonin. If patients are utilizing medications to treat their insomnia, they must agree to abstain from treatment for at least 2 weeks prior to the baseline study, with no plans to recommence treatment for the duration of the trial.
• Use more than 500 mg/day of Aspirin, due to the potential for an interaction with sulthiame
• Concurrent use of drugs with clinically significant QT-interval prolonging effects
• GLP1 receptor agonists for weight loss, unless reached stable dose for 3+ months
• Prior/Concurrent Clinical Study Experience
• Use of another investigational agent within 30 days or 5 half-lives prior to dosing, whichever is longer
• Other Exclusions
• Any condition that in the investigator’s opinion would present an unreasonable risk to the participant, or which would interfere with their participation in the study or confound study interpretation.
• Participant considered by the investigator, for any reason, an unsuitable candidate to receive the investigational treatment or unable or unlikely to understand or comply with the dosing schedule or study evaluations.
• Employment as a commercial driver or operator of heavy or hazardous equipment.
• Typically smoking more than 10 cigarettes or 2 cigars per day, or inability to abstain from smoking during overnight PSG visits.
• History of regular alcohol consumption of more than 14 standard units per week (males) or more than 7 standard units per week (females), or unwillingness to limit alcohol consumption to no greater than 2 units/day (males), 1 unit per day (females). Alcohol is not to be consumed within 3 hours of bedtime or on PSG nights.
• Inability to refrain from > 400mg/day of caffeine consumption for study duration
• History of attempted suicide within 1 year prior to screening, or current suicidal ideation.