Clinical trial NCT04067791: A Study to Investigate the Pharmacokinetics of Prolonged-release Melatonin Compared to Standard, Immediate-release Melatonin in Healthy Adults
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy
Adult
Melatonin
Pharmacokinetic
Absorption
prolonged-release
immediate-release
Lead sponsor: Pharmavite LLC
Sponsor class: INDUSTRY
Collaborators: name: KGK Science Inc.
First posted: 2019-08-26
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Females and males between 18 and 65 years of age at screening
2. BMI between 18.5 to 29.9 kg/m2, inclusive
3. 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
4. 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
5. 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
6. Agrees to maintain current sleep schedule throughout study
7. Agrees to maintain current level of physical activity and diet throughout the study
8. Agrees to comply with all study procedures
9. Agrees to consume standardized meals during Visits 2 and 3
10. Agrees to avoid caffeine intake 24 hours prior to Visits 2 and 3
11. Agrees to avoid alcohol intake 24 hours prior to Visits 2 and 3
12. Healthy as determined by medical history, laboratory results, and physical exam as assessed by QI
13. Agrees to provide informed written consent

Exclusion Criteria:

1. Women who are pregnant, breastfeeding or planning to become pregnant during the course of the trial
2. Allergy, sensitivity, or intolerance to the investigational product's active or inactive ingredients, or the ingredients in the standardized meals
3. Current use of hormonal contraceptives
4. Previous diagnosis of a sleep disorder or use of continuous positive air pressure (C-PAP)
5. Registered with the Canadian National Institute for the Blind (CNIB) and considered as legally blind
6. 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
7. Travel across 1 or more time zones in the last 2 weeks and/or is anticipating more travel
8. Currently experiencing vivid nightmares or sleepwalking
9. Diagnosis of any pineal gland abnormalities or have undergone pinealectomy
10. Current or history of any significant diseases of the gastrointestinal tract
11. Unstable metabolic disease or chronic diseases as assessed by the QI
12. 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
13. Type I or Type II diabetes
14. 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
15. 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
16. Individuals with an autoimmune disease or are immune-compromised
17. Verbal confirmation of medical or neuropsychological condition and/or cognitive impairment that, in the QI's opinion, could interfere with study participation
18. Verbal confirmation of an HIV-, Hepatitis B- and/or C-positive diagnosis
19. 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
20. 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
21. Blood/bleeding disorders as determined by laboratory results
22. An acute gout attack within the past 3 months
23. Current use of prescribed medications listed in the con meds section
24. Current use of over-the-counter medications, supplements, foods and/or drinks listed in the con meds section
25. Use of medical marijuana
26. Use of recreational marijuana unless willing to undergo 1-month washout
27. Use of tobacco products within 1-year of baseline
28. Alcohol or drug abuse within the last 12 months
29. High alcohol intake (average of \>2 standard drinks per day or \>10 standard drinks per week)
30. Clinically significant abnormal laboratory results at screening as assessed by the QI
31. 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
32. Plans to donate blood during the study or within 56 days for males and 84 days for females, the last study visit
33. Participation in other clinical research trials 30 days prior to randomization
34. Individuals who are unable to give informed consent
35. 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

Primary outcomes:
measure: Comparison of the pharmacokinetics of prolonged-release melatonin and immediate-release melatonin by evaluating the area under the curve (AUC 0-10h)
timeFrame: 7 days
measure: Comparison of the pharmacokinetics of prolonged-release melatonin and immediate-release melatonin by evaluating the time to peak concentration (tmax)
timeFrame: 7 days
measure: Comparison of the pharmacokinetics of prolonged-release melatonin and immediate-release melatonin by evaluating the peak concentration (Cmax)
timeFrame: 7 days
measure: Comparison of the pharmacokinetics of prolonged-release melatonin and immediate-release melatonin by evaluating the absorption rate constant
timeFrame: 7 days
measure: Comparison of the pharmacokinetics of prolonged-release melatonin and immediate-release melatonin by evaluating the elimination rate constant
timeFrame: 7 days
measure: Comparison of the pharmacokinetics of prolonged-release melatonin and immediate-release melatonin by evaluating the absorption half-life
timeFrame: 7 days
measure: Comparison of the pharmacokinetics of prolonged-release melatonin and immediate-release melatonin by evaluating the elimination half-life
timeFrame: 7 days
Secondary outcomes:
Other outcomes:
measure: Change in blood pressure after an acute administration of either prolonged-release melatonin or immediate-release melatonin
timeFrame: 7 days
measure: Change in heart rate after an acute administration of either prolonged-release melatonin or immediate-release melatonin
timeFrame: 7 days
measure: Change in weight after an acute administration of either prolonged-release melatonin or immediate-release melatonin
timeFrame: 7 days
measure: Change in body mass index (BMI) after an acute administration of either prolonged-release melatonin or immediate-release melatonin
timeFrame: 7 days
measure: Change in Red Blood Cell (RBC) count after an acute administration of either prolonged-release melatonin or immediate-release melatonin
timeFrame: 7 days
measure: Change in Mean Corpuscular Volume (MCV) after an acute administration of either prolonged-release melatonin or immediate-release melatonin
timeFrame: 7 days
measure: Change in Mean Corpuscular Hemoglobin (MCH) after an acute administration of either prolonged-release melatonin or immediate-release melatonin
timeFrame: 7 days
measure: Change in Mean Corpuscular Hemoglobin Concentration (MCHC) after an acute administration of either prolonged-release melatonin or immediate-release melatonin
timeFrame: 7 days
measure: Change in Hematocrit after an acute administration of either prolonged-release melatonin or immediate-release melatonin
timeFrame: 7 days
measure: Change in Red Cell Distribution Width (RDW) after an acute administration of either prolonged-release melatonin or immediate-release melatonin
timeFrame: 7 days
measure: Change in Hemoglobin (Hb) after an acute administration of either prolonged-release melatonin or immediate-release melatonin
timeFrame: 7 days
measure: Change in neutrophils after an acute administration of either prolonged-release melatonin or immediate-release melatonin
timeFrame: 7 days
measure: Change in lymphocytes after an acute administration of either prolonged-release melatonin or immediate-release melatonin
timeFrame: 7 days
measure: Change in monocytes after an acute administration of either prolonged-release melatonin or immediate-release melatonin
timeFrame: 7 days
measure: Change in eosinophils after an acute administration of either prolonged-release melatonin or immediate-release melatonin
timeFrame: 7 days
measure: Change in basophils after an acute administration of either prolonged-release melatonin or immediate-release melatonin
timeFrame: 7 days
measure: Change in alanine aminotransferase (ALT) after an acute administration of either prolonged-release melatonin or immediate-release melatonin
timeFrame: 7 days
measure: Change in aspartate aminotransferase (AST) after an acute administration of either prolonged-release melatonin or immediate-release melatonin
timeFrame: 7 days
measure: Change in creatinine after an acute administration of either prolonged-release melatonin or immediate-release melatonin
timeFrame: 7 days
measure: Change in electrolytes after an acute administration of either prolonged-release melatonin or immediate-release melatonin
timeFrame: 7 days
measure: Change in estimated glomerular filtration rate (eGFR) after an acute administration of either prolonged-release melatonin or immediate-release melatonin
timeFrame: 7 days
measure: Change in total bilirubin after an acute administration of either prolonged-release melatonin or immediate-release melatonin
timeFrame: 7 days
measure: Change in adverse events after an acute administration of either prolonged-release melatonin or immediate-release melatonin
timeFrame: 7 days
Locations:
city: London
country: Canada
facility: KGK Science Inc.
state: Ontario
Study officials:
affiliation: KGK Science Inc.
name: David Crowley, MD
role: PRINCIPAL_INVESTIGATOR
References: