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

NCT06801379 | Recruiting Early Phase 1

• 1 other identifier: 520241811859849
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Insomnia

Keywords

Melatonin; Insomnia; Pharmacokinetics; Inhaled Therapy

Outcome Measures

Primary Outcomes (1)

• Time to maximum Melatonin concentration

  Time to peak concentration (Tmax) of blood-based melatonin, analysed by melatonin ELISA.

  0-8 hours post-treatment.

Secondary Outcomes (4)

• Melatonin area under the curve

  0-8 hours post-treatment.

• Maximum blood-based melatonin concentration

  0-8 hours post-treatment.

• Melatonin half-life

  0-8 hours post-treatment.

• Daytime sleepiness

  Collected at t0 then every fifteen minutes during the first hour post-treatment, then once hourly until 8 hours post-treatment.

Study Arms (2)

Inhaled Melatonin Arm

EXPERIMENTAL

100 µg daily of inhaled melatonin delivered by pressurized metered dose inhaler for two weeks before habitual bedtime.

Drug: Inhaled Melatonin (100 μg)

Oral Melatonin Arm

ACTIVE COMPARATOR

4 mg daily of orally delivered melatonin tablets for two weeks before habitual bedtime.

Drug: Oral Melatonin (4 mg)

Interventions

Inhaled Melatonin (100 μg) DRUG

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.

Also known as: Melatonin, N-Acetyl-5-methoxytryptamine

Inhaled Melatonin Arm

Oral Melatonin (4 mg) DRUG

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.

Also known as: N-Acetyl-5-methoxytryptamine, Circadin, Melatonin

Oral Melatonin Arm

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Woolcock Institute of Medical Research: lead

Study Sites (1)

Woolcock Institute of Medical Research

Macquarie Park, New South Wales, 2113, Australia

RECRUITING

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Hui Xin Ong, PhD

  Woolcock Institute of Medical Research

  PRINCIPAL INVESTIGATOR

• Ron Grunstein, MBBS MD PhD FRACP

  Woolcock Institute of Medical Research

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hui Xin Ong, PhD

CONTACT

0298053094; huixin.ong@mq.edu.au

Darren Zhao, PhD

CONTACT

0298053094; mat.leslie@woolcock.org.au

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: As this trial is open-label, all study staff and participants will not be blinded.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Scientific Officer, Principal Investigator, Senior Research Fellow

Model Details: Randomised, open-label, crossover trial

Study Record Dates

• First Submitted: January 24, 2025
• First Posted: January 30, 2025
• Study Start: July 1, 2025
• Primary Completion: December 31, 2025
• Study Completion: May 1, 2026
• Last Updated: July 18, 2025

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Time Frame: Non-identifiable IPD will become available one year after the Actual Study Completion Date and will remain available for fifteen years.
• Access Criteria: Following Macquarie University access terms, access restrictions will be limited to appropriate permission, project proposal and approved from the investigator team and data custodian. Any Recipients of the data must obtain project and HREC approval prior to mediated access. The Coordinating Principal Investigator, Dr. Hui Xin Ong, will be retain access the de-identified data, stored on the Macquarie University Research Data Repository (RDR).

Locations

AU (1)