Pharmacokinetics of Intravenous, Rectal, Intravesical, Vaginal, and Transdermal Melatonin in Healthy Female Volunteers

Study Overview
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Brief Summary
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We will investigate the safety and pharmacokinetics of melatonin, when administered rectally, intravesically, vaginally and transdermally. We will recruit 10 healthy female volunteers. The volunteers will have melatonin administered over 5 days; intravenously, rectally, intravesically, vaginally and transdermally. The participants will be followed for 24-48 hours with blood samples and questions about adverse events. There will be a wash-out between each session of a minimum of 7 days.

Official Title
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Pharmacokinetics of Intravenous, Rectal, Intravesical, Vaginal, and Transdermal Administration of Exogenous Melatonin in Healthy Female Volunteers: a Crossover Study

Conditions
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Melatonin, Pharmacokinetics, Safety

Intervention / Treatment
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* Drug: Melatonin 25 mg


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Healthy female 20-40 years old BMI 18-30 Exclusion criteria: Inability to understand Danish, written or spoken. Current use of melatonin or other hypnotics/sedatives Current pregnancy (a positive urine-HCG; the subjects will be tested prior to each study session) Breast feeding Current alcohol or drug abuse (defined as over 5 units of alcohol per day, or any usage of illegal drugs) Mental illness (defined as being in medical treatment) Serious comorbidity (American Society of Anesthesiologists (ASA) physical status 3-4) Participation in other clinical trials less than 1 month prior to current study Night-shift work within the last 14 days prior to study Planned night-shift work within the study period Known and diagnosed sleep-disorder (defined as being in current medical treatment) Plasma hemoglobin <7.8 mmol/L (measured when screening participants)

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

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: Non-Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Each volunteer will have melatonin administered through all five routes of administration, and will have a wash-out of a minimum of 7 days between each administration.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intravenous melatonin<br>Intravenous administration, making it possible to calculate bioavailability for other routes of administration | Drug: Melatonin 25 mg<br>* 24-48 hour monitoring of plasma melatonin as well as adverse events.<br>|
| Experimental: Rectal melatonin<br>Rectal administration of melatonin | Drug: Melatonin 25 mg<br>* 24-48 hour monitoring of plasma melatonin as well as adverse events.<br>|
| Experimental: Intravesical melatonin<br>Intravesical administration of melatonin | Drug: Melatonin 25 mg<br>* 24-48 hour monitoring of plasma melatonin as well as adverse events.<br>|
| Experimental: Vaginal melatonin<br>Vaginal administration of melatonin | Drug: Melatonin 25 mg<br>* 24-48 hour monitoring of plasma melatonin as well as adverse events.<br>|
| Experimental: Transdermal melatonin<br>Transdermal administration of melatonin | Drug: Melatonin 25 mg<br>* 24-48 hour monitoring of plasma melatonin as well as adverse events.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of melatonin | Plasma concentration of melatonin | Baseline, 0 minutes, 10 minutes, 20 minutes, 30 minutes, 40 minutes, 50 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 24 hours | 
| Plasma concentration of melatonin | Plasma concentration of melatonin | Baseline, 0 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Karolinska Sleepiness Scale | Scale which evaluates tiredness of participants | 0 minutes, once hourly for 8 hours, and again at 24 hours | 
| Simple Reaction Time Test | A simple reaction time test which measures the participants' reaction time; they are looking at a red lamp, and need to react when it changes to green. | 0 minutes, once hourly for 8 hours, and again at 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Melatonin, Safety, Pharmacokinetics