A Pharmacokinetic Study of Intravenous and Intranasal Oxytocin in Healthy Subjects

The main purpose of this study is to sample blood and model the plasma pharmacokinetics (PK) of a single dose of intravenous (IV) oxytocin and a single dose of intranasal (i.n.) oxytocin.

This is an unblinded study of subjects, all of whom will receive an intravenous (IV) infusion and intranasal (i.n.) dose of oxytocin (a naturally occurring hormone that is made in the brain) with blood samples taken thereafter in order to create a formula to describe the concentrations of oxytocin in the blood over time (pharmacokinetics).

In this study healthy volunteers and people are recruited for a two day study. Each study participant will have 2 IV catheters placed (one in each arm) for the day of IV oxytocin dosing and 1 IV catheter on the day of i.n. oxytocin dosing. After placement of the IV catheters, an infusion of oxytocin will be given over a 30 minute period. Blood samples will be taken after the infusion begins and several times during and after the infusion. The blood will be drawn through the IV catheter not used for the oxytocin infusion. For the intranasal oxytocin administration day, 1 IV catheter will be placed and several blood samples will be taken after administration.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer Study
• Intervention / Treatment: Drug: intravenous oxytocin; Drug: intranasal oxytocin

Detailed Description

This is an unblinded, sequential study of subjects; all participants will receive an infusion of oxytocin and intranasal administration of oxytocin with blood samples taken thereafter in order to create a formula to describe the concentrations of oxytocin in the blood over time (pharmacokinetics). In this study healthy volunteers. Participants will come to the Clinical Research Unit (CRU) on study day 1 and have two IVs inserted; one in each arm. Participants will get a 30 minute infusion through one of the IV catheters of oxytocin and blood will be taken several times over the next 120 minutes, plasma separated, and the amount of oxytocin measured in the plasma samples. Participants will come to the CRU on study day 2 and have one IV inserted; in the arm. Participants will self administer intranasal oxytocin and blood will be taken several times over the next 60 minutes and the amount of oxytocin measured in the plasma samples. This information will be analyzed by another group at Stanford University under a data sharing agreement between the institutions and funded by a grant from the National Institutes of Health. Compartmental modeling will be performed using NONMEM to describe the change in oxytocin concentrations over time. The effect of subject age, sex, race, ethnicity and weight on the pharmacokinetics of oxytocin will be examined, since these factors can affect pharmacokinetics and are important to better adjust the dose of drug to the individual.

The main purpose of this study is to determine the amount of oxytocin in plasma after IV and i.n. administration.

The research participants will not benefit from this study, but the knowledge investigators get will be important to adjust oxytocin dose to individuals, and to be able to calculate plasma oxytocin concentrations after various doses in the future. The sample size chosen is needed to get an accurate estimate for the parameters in the pharmacokinetic model for the population, not just the subjects in this study.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male or female > 18 and < 75 years of age, Body Mass Index (BMI) <40.
• Generally in good health as determined by the Principal Investigator based on prior medical history, American Society of Anesthesiologists physical status 1 or 2.
• For healthy volunteers, normal blood pressure (systolic 100-140 mmHg; diastolic 60-90 mmHg) resting heart rate 45-90 beats per minute) without medication. For those with hypertension, blood pressure controlled with anti-hypertensive medication and with a resting heart rate 45-100 beats per minute.
• Female subjects of child-bearing potential and those < 1 year post-menopausal, must be practicing highly effective methods of birth control such as hormonal methods (e.g., combined oral, implantable, injectable, or transdermal contraceptives), double barrier methods (e.g., condoms, sponge, diaphragm, or vaginal ring plus spermicidal jellies or cream), or total abstinence from heterosexual intercourse for a minimum of 1 full cycle before study drug administration.

Exclusion Criteria:

• Hypersensitivity, allergy, or significant reaction to any ingredient of Pitocin®
• Any disease, diagnosis, or condition (medical or surgical) that, in the opinion of the Principal Investigator, would place the subject at increased risk (active gynecologic disease in which increased tone would be detrimental e.g., uterine fibroids with ongoing bleeding), compromise the subject's compliance with study procedures, or compromise the quality of the data
• Women who are pregnant (positive result for urine pregnancy test at visit 1), women who are currently nursing or lactating, women that have been pregnant within 2 years
• Subjects with neuropathy, chronic pain (being treated on a daily basis), diabetes mellitus, or taking benzodiazepines or pain medications on a daily basis.
• Subjects with current or history of ventricular tachycardia, atrial fibrillation or prolonged QT interval.
• Subjects with past or current history of hyponatremia or at risk for hyponatremia; anyone taking thiazide diuretics, loop diuretics, combination diuretics, lithium, carbamazepine, enalapril, Ramipril, celecoxib, temazepam, gliclazide, glimepiride, glibenclamide, glipizide, omeprazole, pantoprazole, desmopressin, Selective serotonin reuptake inhibitors (SSRI's) , Monoamine oxidase inhibitors (MAOI), or the recreational drug ecstasy.
• Subjects with a known latex allergy.
• History of chronic nasal obstruction or local pathology in nostril pathway which, in the opinion of the investigator, would prevent appropriate nasal administration of the study drug.
• Use of over the counter nasal products (ie. Saline spray, Neti-Pot, etc.) or intranasal corticosteroid medications during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oxytocin Administration (Intravenous, then Intranasal); Oxytocin 14 micrograms infusion over 30 minutes on first study day. Oxytocin 102 micrograms by intranasal spray on second study day.	Drug: intravenous oxytocin; Oxytocin given by intravenous route; Other Names: Pitocin; Drug: intranasal oxytocin; Oxytocin given by intranasal administration; Other Names: TNX-1900

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Oxytocin Concentration 2 Minutes After Infusion Initiated	Blood will be sampled at specified intervals during and after the infusion. Plasma will be separated, rapidly frozen, and later analyzed for oxytocin concentration	2 minutes after oxytocin infusion initiated
Plasma Oxytocin Concentration 5 Minutes After Infusion Initiated	Blood will be sampled at specified intervals during and after the infusion. Plasma will be separated, rapidly frozen, and later analyzed for oxytocin concentration	5 minutes after oxytocin infusion initiated
Plasma Oxytocin Concentration 10 Minutes After Infusion Initiated	Blood will be sampled at specified intervals during and after the infusion. Plasma will be separated, rapidly frozen, and later analyzed for oxytocin concentration	10 minutes after oxytocin infusion initiated
Plasma Oxytocin Concentration 20 Minutes After Infusion Initiated	Blood will be sampled at specified intervals during and after the infusion. Plasma will be separated, rapidly frozen, and later analyzed for oxytocin concentration	20 minutes after oxytocin infusion initiated
Plasma Oxytocin Concentration 30 Minutes After Infusion Initiated	Blood will be sampled at specified intervals during and after the infusion. Plasma will be separated, rapidly frozen, and later analyzed for oxytocin concentration	30 minutes after oxytocin infusion initiated
Plasma Oxytocin Concentration 40 Minutes After Infusion Initiated	Blood will be sampled at specified intervals during and after the infusion. Plasma will be separated, rapidly frozen, and later analyzed for oxytocin concentration	40 minutes after oxytocin infusion initiated
Plasma Oxytocin Concentration 50 Minutes After Infusion Initiated	Blood will be sampled at specified intervals during and after the infusion. Plasma will be separated, rapidly frozen, and later analyzed for oxytocin concentration	50 minutes after oxytocin infusion initiated
Plasma Oxytocin Concentration 65 Minutes After Infusion Initiated	Blood will be sampled at specified intervals during and after the infusion. Plasma will be separated, rapidly frozen, and later analyzed for oxytocin concentration	65 minutes after oxytocin infusion initiated
Plasma Oxytocin Concentration 90 Minutes After Infusion Initiated	Blood will be sampled at specified intervals during and after the infusion. Plasma will be separated, rapidly frozen, and later analyzed for oxytocin concentration	90 minutes after oxytocin infusion initiated
Plasma Oxytocin Concentration 120 Minutes After Infusion Initiated	Blood will be sampled at specified intervals during and after the infusion. Plasma will be separated, rapidly frozen, and later analyzed for oxytocin concentration	120 minutes after oxytocin infusion initiated
Plasma Oxytocin Concentration 1 Minute After First Intranasal Puffs	Blood will be sampled at specified intervals after the intranasal administration of oxytocin. Plasma will be separated, rapidly frozen, and later analyzed for oxytocin concentration	1 minute after intranasal oxytocin administration
Plasma Oxytocin Concentration 2 Minutes After First Intranasal Puffs	Blood will be sampled at specified intervals after the intranasal administration of oxytocin. Plasma will be separated, rapidly frozen, and later analyzed for oxytocin concentration	2 minutes after intranasal oxytocin administration
Plasma Oxytocin Concentration 5 Minutes After First Intranasal Puffs	Blood will be sampled at specified intervals after the intranasal administration of oxytocin. Plasma will be separated, rapidly frozen, and later analyzed for oxytocin concentration	5 minutes after intranasal oxytocin administration
Plasma Oxytocin Concentration 7 Minutes After First Intranasal Puffs	Blood will be sampled at specified intervals after the intranasal administration of oxytocin. Plasma will be separated, rapidly frozen, and later analyzed for oxytocin concentration	7 minutes after intranasal oxytocin administration
Plasma Oxytocin Concentration 10 Minutes After First Intranasal Puffs	Blood will be sampled at specified intervals after the intranasal administration of oxytocin. Plasma will be separated, rapidly frozen, and later analyzed for oxytocin concentration	10 minutes after intranasal oxytocin administration
Plasma Oxytocin Concentration 15 Minutes After First Intranasal Puffs	Blood will be sampled at specified intervals after the intranasal administration of oxytocin. Plasma will be separated, rapidly frozen, and later analyzed for oxytocin concentration	15 minutes after intranasal oxytocin administration
Plasma Oxytocin Concentration 20 Minutes After First Intranasal Puffs	Blood will be sampled at specified intervals after the intranasal administration of oxytocin. Plasma will be separated, rapidly frozen, and later analyzed for oxytocin concentration	20 minutes after intranasal oxytocin administration
Plasma Oxytocin Concentration 25 Minutes After First Intranasal Puffs	Blood will be sampled at specified intervals after the intranasal administration of oxytocin. Plasma will be separated, rapidly frozen, and later analyzed for oxytocin concentration	25 minutes after intranasal oxytocin administration
Plasma Oxytocin Concentration 35 Minutes After First Intranasal Puffs	Blood will be sampled at specified intervals after the intranasal administration of oxytocin. Plasma will be separated, rapidly frozen, and later analyzed for oxytocin concentration	35 minutes after intranasal oxytocin administration
Plasma Oxytocin Concentration 45 Minutes After First Intranasal Puffs	Blood will be sampled at specified intervals after the intranasal administration of oxytocin. Plasma will be separated, rapidly frozen, and later analyzed for oxytocin concentration	45 minutes after intranasal oxytocin administration
Plasma Oxytocin Concentration 60 Minutes After First Intranasal Puffs	Blood will be sampled at specified intervals after the intranasal administration of oxytocin. Plasma will be separated, rapidly frozen, and later analyzed for oxytocin concentration	60 minutes after intranasal oxytocin administration

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: James C Eisenach, MD, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2023
• Primary Completion (Actual): November 1, 2023
• Study Completion (Actual): November 1, 2023

Study Registration Dates

• First Submitted: December 20, 2022
• First Submitted That Met QC Criteria: December 20, 2022
• First Posted (Actual): January 5, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 24, 2025
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Chronic Pain; Acute Pain; Intravenous Oxytocin; Intranasal Oxytocin
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: IRB00089938; 1P01NS119159-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Plan Description: Statistical programs in the data analysis will be written in R. The software and anonymized data will be included both as digital supplements in the published papers and will be posted on GitHub under github.com/StevenLShafer. Interested investigators will be able to reproduce the published analyses from these files. Consistent with the posting of software and data to the OpenTCI initiative, the software and de-identified data will be made available with "no strings attached," enabling investigators to freely use the data to inform or supplement additional research without restriction. Data to be made available are oxytocin dose, times of sampling (relative to the start of dosing), plasma oxytocin concentrations at those times for each subject, and age, weight, and sex for each subject.
• IPD Sharing Time Frame: Data will become available upon publication or upon posting results in ClinicalTrials.gov, whichever comes first, with no expiration.
• IPD Sharing Access Criteria: These data are freely shared to all and will be posted at the URL below
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No