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

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

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.

Study Overview

• Status: Completed
• Conditions: Pharmacokinetics; Safety; Melatonin
• Intervention / Treatment: Drug: Melatonin 25 mg

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Herlev, Denmark, 2000
    • Herlev Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Dennis Bregner Zetner
• Collaborators: Herlev Hospital; Copenhagen University Hospital, Denmark; RepoCeuticals ApS
• Investigators: Principal Investigator: Dennis B Zetner, MD, Center for Perioperative Optimization, Department of Surgery, Herlev Hospital, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2018
• Primary Completion (Actual): February 21, 2019
• Study Completion (Actual): February 21, 2019

Study Registration Dates

• First Submitted: April 16, 2018
• First Submitted That Met QC Criteria: May 8, 2018
• First Posted (Actual): May 9, 2018

Study Record Updates

• Last Update Posted (Actual): April 30, 2019
• Last Update Submitted That Met QC Criteria: April 29, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Safety; Melatonin; Pharmacokinetics
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Protective Agents; Antioxidants; Melatonin
• Other Study ID Numbers: 2017-000997-13

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No