Kinetic of Melatonin Subsequent to the Consumption of Melatonin-rich Food Supplements

Study Overview
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Brief Summary
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This study is conducted to clinically document the melatonin bioavailability of two dietary supplements containing melatonin : one prolonged release tablet dosed at 1.9mg and one spray dosed at 1mg for 2 oral sprays.

Official Title
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Randomized, Open-label Bioavailability Study of the Kinetics of Plasma, Urinary and Salivary Concentrations of Melatonin and 6-sulfatoxymelatonin Subsequent to the Consumption of Melatonin-rich Food Supplements With Different Galenic Forms

Conditions
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Melatonin Bioavailability

Intervention / Treatment
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* Dietary Supplement: a prolonged release tablet and a spray containing melatonin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male between the ages of 18 and 45, In good general health, i.e., free of chronic conditions and not taking medication at the time of inclusion and/or long-term, Over 70 kg and with a body mass index between 18.5 and 24.9, Able and willing to participate in the research by complying with the procedures of the protocol, in particular concerning the taking of the product under study and the performance of sequential blood tests, Having freely signed the consent form after adequate information on the proposed study, in accordance with Good Clinical Practice and after submission of the information leaflet, Affiliated to a social security scheme or similar. Exclusion Criteria: Smoker, Drug addict, Subject with an alcohol consumption of more than 2 glasses per day, Taking a drug treatment or melatonin or a product containing melatonin within 48 hours prior to a kinetics visit, Known organic or functional abnormality of the urinary tree, Any medical condition that would involve a change in melatonin metabolism: Drug intake: Fluvoxamine, 5- or 8-methoxypsoralen, cimetidine, carbamazepine and rifampicin, analgesics, Liver abnormality known or detected at the screening visit and judged to be clinically significant by the investigator, Known autoimmune disease, Subject assessed as moderately or definitely evening type, Known hypertension (>140/90), Diagnosis of migraine by a health professional according to the International Headache Society (IHS) criteria revised in 2004, Wuth a sleep disorder, Thyroid dysfunction, hyperglycemia or anemia judged to be clinically significant by the investigator, Blood donation within one month prior to inclusion, A known organic or psychological abnormality (including a history of severe depression) that may bias the results of the study as judged by the investigator, Workers with atypical working hours (night work, staggered working hours), Known allergy or intolerance to any of the components of the product, Psychological or linguistic inability to understand and sign informed consent, Participant in another interventional clinical trial or during a period of exclusion from a previous clinical trial, Under legal protection (guardianship, curatorship) or deprived of his rights as a result of the administrative or judicial decision, Subject who has reached the maximum threshold for compensation for research provided for in the regulations.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: spray before tablet<br> | Dietary Supplement: a prolonged release tablet and a spray containing melatonin<br>* prolonged release tablet is dosed at 1.9mg and spray is dosed at 1mg for 2 oral sprays.<br>|
| Experimental: tablet before spray<br> | Dietary Supplement: a prolonged release tablet and a spray containing melatonin<br>* prolonged release tablet is dosed at 1.9mg and spray is dosed at 1mg for 2 oral sprays.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| evolution of the plasma melatonin concentration | the change in plasma melatonin concentration | over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| evolution of the plasma concentration of 6-sulfatoxymelatonin | the change in plasma 6-sulfatoxymelatonin concentration | over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray. | 
| evolution of the urinary concentration of 6-sulfatoxymelatonin | the change in urinary 6-sulfatoxymelatonin concentration | over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray. | 
| evolution of the salivary concentration of melatonin | the change in salivary melatonin concentration | over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray. | 
| adverse events | adverse events | during study participation, maximum 45 days | 
| plasma melatonin AUC | Area Under the Curve of plasma melatonin | over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray. | 
| plasma 6-sulfatoxymelatonin AUC | Area Under the Curve of plasma 6-sulfatoxymelatonin | over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray. | 
| urinary 6-sulfatoxymelatonin AUC | Area Under the Curve of urinary 6-sulfatoxymelatonin | over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray. | 
| salivary melatonin AUC | Area Under the Curve of salivary melatonin | over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray. | 
| plasma melatonin Cmax | Peak concentration of plasma melatonin | over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray. | 
| plasma 6-sulfatoxymelatonin Cmax | Peak concentration of plasma 6-sulfatoxymelatonin | over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray. | 
| urinary 6-sulfatoxymelatonin Cmax | Peak concentration of urinary 6-sulfatoxymelatonin | over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray. | 
| salivary melatonin Cmax | Peak concentration of salivary melatonin | over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray. | 
| plasma melatonin Tmax | Time take to reach Cmax of plasma melatonin | over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray. | 
| plasma 6-sulfatoxymelatonin Tmax | Time take to reach Cmax of plasma 6-sulfatoxymelatonin | over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray. | 
| urinary 6-sulfatoxymelatonin Tmax | Time take to reach Cmax of urinary 6-sulfatoxymelatonin | over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray. | 
| salivary melatonin Tmax | Time take to reach Cmax of salivary melatonin | over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray. | 
| plasma melatonin half life | time required for the concentration of plasma melatonin to decrease to half of its starting dose | over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray. | 
| plasma 6-sulfatoxymelatonin half life | time required for the concentration of plasma 6-sulfatoxymelatonin to decrease to half of its starting dose | over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray. | 
| urinary 6-sulfatoxymelatonin half life | time required for the concentration of urinary 6-sulfatoxymelatonin to decrease to half of its starting dose | over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray. | 
| salivary melatonin half life | time required for the concentration of salivary melatonin to decrease to half of its starting dose | over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray. |