A Study to Investigate the Pharmacokinetics of Prolonged-release Melatonin Compared to Standard, Immediate-release Melatonin in Healthy Adults

Study Overview
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Brief Summary
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A study comparing the pharmacokinetics of prolonged-release melatonin versus standard, immediate-release melatonin. Multiple blood draws over a 10-hour period will be analysed to determine the area under the curve, time to peak concentration, peak concentration, absorption rate constant, elimination rate constant, absorption half-life, and elimination half-life. Vital signs, hematology parameters, clinical chemistry parameters, and incidence of adverse events are also analysed.

Official Title
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A Randomized, Double-blind, Comparator-controlled, Cross-over Study to Investigate the Pharmacokinetics of Prolonged-release Melatonin Compared to Standard, Immediate-release Melatonin in Healthy Adults

Conditions
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Healthy

Intervention / Treatment
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* Dietary Supplement: Prolonged-Release Melatonin
* Dietary Supplement: Immediate-Release Melatonin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females and males between 18 and 65 years of age at screening BMI between 18.5 to 29.9 kg/m2, inclusive Female participant is not of child-bearing potential, defined as females who have undergone a sterilization procedure (e.g. hysterectomy, bilateral oophorectomy, bilateral tubal ligation, total endometrial ablation) or have been post-menopausal (natural or surgically) for at least 1 year prior to screening Or, Females of child-bearing potential must have a negative baseline urine pregnancy test and agree to use a medically approved method of birth control for the duration of the study. Acceptable methods of birth control include: e. Non-hormonal intrauterine devices f. Double-barrier method g. Non-heterosexual lifestyle or agrees to use contraception if planning on changing to heterosexual partner(s) h. Vasectomy of partner at least 6 months prior to screening Male participants must agree to the use of condoms unless partner is using an acceptable form of female contraception as defined in Inclusion #3 or a form of hormonal birth control during the study treatment period and for at least 7 days after completion of the study Have a regular sleep-wake cycle with a bedtime between 9:00 pm and 12:00 am and receive between 7 and 8 hours of sleep for at least 3 weeks Agrees to maintain current sleep schedule throughout study Agrees to maintain current level of physical activity and diet throughout the study Agrees to comply with all study procedures Agrees to consume standardized meals during Visits 2 and 3 Agrees to avoid caffeine intake 24 hours prior to Visits 2 and 3 Agrees to avoid alcohol intake 24 hours prior to Visits 2 and 3 Healthy as determined by medical history, laboratory results, and physical exam as assessed by QI Agrees to provide informed written consent Exclusion Criteria: Women who are pregnant, breastfeeding or planning to become pregnant during the course of the trial Allergy, sensitivity, or intolerance to the investigational product's active or inactive ingredients, or the ingredients in the standardized meals Current use of hormonal contraceptives Previous diagnosis of a sleep disorder or use of continuous positive air pressure (C-PAP) Registered with the Canadian National Institute for the Blind (CNIB) and considered as legally blind Current employment that calls for rotating shift work or shift work that will disrupt normal circadian rhythm or have worked shift work in the last 3 weeks Travel across 1 or more time zones in the last 2 weeks and/or is anticipating more travel Currently experiencing vivid nightmares or sleepwalking Diagnosis of any pineal gland abnormalities or have undergone pinealectomy Current or history of any significant diseases of the gastrointestinal tract Unstable metabolic disease or chronic diseases as assessed by the QI Verbal confirmation of current or pre-existing thyroid condition. Treatment on a stable dose of medication for at least 3 months will be considered by the QI Type I or Type II diabetes Significant cardiovascular event in the past 6 months. Participants with no significant cardiovascular event on stable medication may be included after assessment by the QI on a case-by-case basis Cancer, except skin cancers completely excised with no chemotherapy or radiation with a follow up that is negative. Volunteers with cancer in full remission for more than 5 years after diagnosis are acceptable Individuals with an autoimmune disease or are immune-compromised Verbal confirmation of medical or neuropsychological condition and/or cognitive impairment that, in the QI's opinion, could interfere with study participation Verbal confirmation of an HIV-, Hepatitis B- and/or C-positive diagnosis History of or current diagnosis with kidney and/or liver diseases as assessed by the QI on a case-by-case basis, with the exception of history of kidney stones symptom-free for 6 months Major surgery in the past 3 months or individuals who have planned surgery, that may impact the outcomes of the study, during the course of the trial. Participants will be considered on a case-by-case basis by the QI Blood/bleeding disorders as determined by laboratory results An acute gout attack within the past 3 months Current use of prescribed medications listed in the con meds section Current use of over-the-counter medications, supplements, foods and/or drinks listed in the con meds section Use of medical marijuana Use of recreational marijuana unless willing to undergo 1-month washout Use of tobacco products within 1-year of baseline Alcohol or drug abuse within the last 12 months High alcohol intake (average of >2 standard drinks per day or >10 standard drinks per week) Clinically significant abnormal laboratory results at screening as assessed by the QI Blood donation within the past 6 months will be assessed on a case by case basis by the QI depending on volume and frequency of donation, and laboratory parameters Plans to donate blood during the study or within 56 days for males and 84 days for females, the last study visit Participation in other clinical research trials 30 days prior to randomization Individuals who are unable to give informed consent Any other active or unstable medical condition, that, in the opinion of the QI, may adversely affect the participant's ability to complete the study or its measures or pose a significant risk to the participant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prolonged-Release melatonin then Immediate-release melatonin<br> | Dietary Supplement: Prolonged-Release Melatonin<br>* 4.47 mg melatonin in a bi-layer prolonged-release capsule<br>Dietary Supplement: Immediate-Release Melatonin<br>* 4.47 mg melatonin in a standard release bi-layer capsule<br>|
| Experimental: Immediate-Release Melatonin then Prolonged-Release Melatonin<br> | Dietary Supplement: Prolonged-Release Melatonin<br>* 4.47 mg melatonin in a bi-layer prolonged-release capsule<br>Dietary Supplement: Immediate-Release Melatonin<br>* 4.47 mg melatonin in a standard release bi-layer capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the pharmacokinetics of prolonged-release melatonin and immediate-release melatonin by evaluating the area under the curve (AUC 0-10h) |  | 7 days | 
| Comparison of the pharmacokinetics of prolonged-release melatonin and immediate-release melatonin by evaluating the time to peak concentration (tmax) |  | 7 days | 
| Comparison of the pharmacokinetics of prolonged-release melatonin and immediate-release melatonin by evaluating the peak concentration (Cmax) |  | 7 days | 
| Comparison of the pharmacokinetics of prolonged-release melatonin and immediate-release melatonin by evaluating the absorption rate constant |  | 7 days | 
| Comparison of the pharmacokinetics of prolonged-release melatonin and immediate-release melatonin by evaluating the elimination rate constant |  | 7 days | 
| Comparison of the pharmacokinetics of prolonged-release melatonin and immediate-release melatonin by evaluating the absorption half-life |  | 7 days | 
| Comparison of the pharmacokinetics of prolonged-release melatonin and immediate-release melatonin by evaluating the elimination half-life |  | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy, Adult, Melatonin, Pharmacokinetic, Absorption, prolonged-release, immediate-release