RecruitingEarly Phase 1NCT06801379

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

A Novel Inhaled Formulation of Melatonin to Treat Adults With Insomnia Disorder: a Randomised Open-Label Crossover Trial

Sponsor

Woolcock Institute of Medical Research

Enrollment

5 participants

Start Date

Jul 1, 2025

Study Type

INTERVENTIONAL

Conditions

Insomnia

Summary

The goal of this clinical trial is to explore the potential benefits of an inhaled version of melatonin compared to oral melatonin tablets on adults with insomnia. The main question the trial aims to answer: is the time required for inhaled melatonin to reach peak concentration in the blood and then be eliminated from body different to that of oral melatonin tablets, in adults with insomnia? 5 participants will: * Visit the research institute for a screening visit and for a daytime visit to take a melatonin treatment then provide blood samples over the course of 8 hours for each study drug treatment (3 visits in total) * Take 100 μg of inhaled melatonin (2 inhaler puffs) once * Take a 4 mg of oral melatonin (2 tablets) once

Eligibility

Min Age: 55 Years

Inclusion Criteria5

Diagnosis of insomnia disorder as defined by the DSM-5 (difficulty initiating or maintaining sleep or waking up too early for at least 3 nights per week, for at least 3 months, with adequate opportunity and circumstances for sleep and at least one 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 nights per week in the previous 4 weeks.
Able to provide informed electronic consent.
Fluent English literacy.
Adults aged 55+ years old.

Exclusion Criteria17

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 with insomnia will be allowed).
Circadian disorders, narcolepsy, severe restless legs syndrome, and REM sleep behaviour disorder or uncontrolled psychiatric disorders.
History of attempted suicide or current suicide ideation (indicated by a score >0 on Q9 of the Patient Health Questionnaire-9) at pre-screening.
Objective cognitive decline measured by scoring ≤26 on the Montreal Cognitive Assessment (MoCA)
Regular shift work, jet lag or trans-meridian travel (over 2h time difference) in the past week before randomisation.
Pregnancy or lactation. Female participants of childbearing potential with a fertile sexual partner must have a negative serum pregnancy test result at the screening visit. Women will be advised to use contraception for the duration of the study.
Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical trial due to safety concerns or compliance with clinical study procedures.
Currently participating in or has participated in a research study of an investigational 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 and Z-drugs), and other medications that can cause additive sedation (e.g. sedating antihistamines, tricyclic antidepressants, antipsychotics) within 14 days or 4-5 half-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 the clinical trial.
Use of antidepressant medications for treatment of low mood for less than one year or dose changes (escalation or tapering) or change in antidepressant medications within the past year.
Regular use opioids within 14 days or 4-5 half-lives (whichever is longer) of starting the clinical trial.
Ongoing use of THC- or CBD-containing products within 14 days prior to the start of the 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 trial period).
Regular use of drugs that are CYP1A2 inhibitors (e.g. amiodarone, cimetidine, ciprofloxacin, fluvoxamine) or CYP1A2 inducers (e.g. carbamazepine, phenobarbital, rifampin, tobacco).

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Interventions

DRUGInhaled Melatonin (100 μg)

An orally inhaled formulation of melatonin delivered by pressurised metered dose inhaler (pMDI) to be taken before bedtime. The pMDI will deliver a total of 100 μg of inhaled melatonin (2 x 50 μg/actuation). The investigational product is produced under Good Manufacturing Practice by Ab Initio Pharma Pty Ltd, a GMP certified manufacturer of pharmaceutical products.

DRUGOral Melatonin (4 mg)

Two orally ingested tablets each containing 2 mg of melatonin (4 mg total) to be taken before bedtime. The investigational product is manufactured under Good Manufacturing Practice and is compliant with the TGA Therapeutic Order #101 that stipulates quality control requirements for capsule and pill-based products used in Australia.