A Novel Inhaled Formulation of Melatonin to Treat Adults With Insomnia: Efficacy Study

Inclusion Criteria:

• Diagnosis of insomnia disorder as defined by the DSM-5 (difficulty initiating ormaintaining sleep or waking up too early for at least 3 nights per week, for atleast 3 months, with adequate opportunity and circumstances for sleep and at leastone daytime impairment related to the sleep difficulty) and a score ≥15 on the ISI.

• History of subjective sleep onset latency (sSOL) ≥30 minutes on at least 3 nightsper week in the previous 4 weeks.

• Able to provide informed electronic consent.

• Fluent English literacy.

• Adults aged 55+ years old.

Exclusion Criteria:

• People highly dependent on medical care as determined by a medical officer.

• Untreated moderate-severe sleep apnoea as diagnosed using in-home wrist oximetry (oxygen desaturation index>15, ongoing effectively treated sleep apnoea withinsomnia will be allowed).

• Circadian disorders, narcolepsy, severe restless legs syndrome, and REM sleepbehaviour disorder or uncontrolled psychiatric disorders.

• History of attempted suicide or current suicide ideation (indicated by a score >0 onQ9 of the Patient Health Questionnaire-9) at pre-screening.

• Objective cognitive decline measured by scoring ≤26 on the Montreal CognitiveAssessment (MoCA)

• Regular shift work, jet lag or trans-meridian travel (over 2h time difference) inthe past week before randomisation.

• Pregnancy or lactation. Female participants of childbearing potential with a fertilesexual partner must have a negative serum pregnancy test result at the screeningvisit. Women will be advised to use contraception for the duration of the study.

• Any other condition that would, in the Investigator's judgment, contraindicate thepatient's participation in the clinical trial due to safety concerns or compliancewith clinical study procedures.

• Currently participating in or has participated in a research study of aninvestigational agent or device within 4 weeks of enrolment.

• Ongoing use of anti-psychotic medication, bosentan, efavirenz, etravirine,modafinil, rifampin, carbamazepine or illicit stimulants.

• Regular use of hypnotics (including melatonin, valerian, kava, benzodiazepines andZ-drugs), and other medications that can cause additive sedation (e.g. sedatingantihistamines, tricyclic antidepressants, antipsychotics) within 14 days or 4-5half-lives (whichever is longer) of starting the clinical trial.

• Regular use of psychostimulants (e.g., dexamfetamine, lisdexamfetamine,methylphenidate) or non-amphetamine psychostimulants (e.g., armodafinil, modafinil,atomoxetine) within 14 days or 4-5 half-lives (whichever is longer) of starting theclinical trial.

• Use of antidepressant medications for treatment of low mood for less than one yearor dose changes (escalation or tapering) or change in antidepressant medicationswithin the past year.

• Regular use opioids within 14 days or 4-5 half-lives (whichever is longer) ofstarting the clinical trial.

• Ongoing use of THC- or CBD-containing products within 14 days prior to the start ofthe trial.

• Dependence or any other drug or alcohol dependence within the past two years (alcohol to be limited to no more than 2 standard drinks per day during trialperiod).

• Regular use of drugs that are CYP1A2 inhibitors (e.g. amiodarone, cimetidine,ciprofloxacin, fluvoxamine) or CYP1A2 inducers (e.g. carbamazepine, phenobarbital,rifampin, tobacco).