Clinical trial NCT05672667: A Pharmacokinetic Study of Intravenous and Intranasal Oxytocin in Healthy Subjects
Official title: A Pharmacokinetic Study of Intravenous and Intranasal Oxytocin in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer Study
Keywords: Acute Pain
Chronic Pain
Intravenous Oxytocin
Intranasal Oxytocin
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2023-01-05
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Each subject will receive 14 micrograms of oxytocin intravenously over 30 minutes and 102 micrograms of oxytocin intranasally.
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Plasma Oxytocin Concentration 2 Minutes After Infusion Initiated
timeFrame: 2 minutes after oxytocin infusion initiated
measure: Plasma Oxytocin Concentration 5 Minutes After Infusion Initiated
timeFrame: 5 minutes after oxytocin infusion initiated
measure: Plasma Oxytocin Concentration 10 Minutes After Infusion Initiated
timeFrame: 10 minutes after oxytocin infusion initiated
measure: Plasma Oxytocin Concentration 20 Minutes After Infusion Initiated
timeFrame: 20 minutes after oxytocin infusion initiated
measure: Plasma Oxytocin Concentration 30 Minutes After Infusion Initiated
timeFrame: 30 minutes after oxytocin infusion initiated
measure: Plasma Oxytocin Concentration 40 Minutes After Infusion Initiated
timeFrame: 40 minutes after oxytocin infusion initiated
measure: Plasma Oxytocin Concentration 50 Minutes After Infusion Initiated
timeFrame: 50 minutes after oxytocin infusion initiated
measure: Plasma Oxytocin Concentration 65 Minutes After Infusion Initiated
timeFrame: 65 minutes after oxytocin infusion initiated
measure: Plasma Oxytocin Concentration 90 Minutes After Infusion Initiated
timeFrame: 90 minutes after oxytocin infusion initiated
measure: Plasma Oxytocin Concentration 120 Minutes After Infusion Initiated
timeFrame: 120 minutes after oxytocin infusion initiated
measure: Plasma Oxytocin Concentration 1 Minute After First Intranasal Puffs
timeFrame: 1 minute after intranasal oxytocin administration
measure: Plasma Oxytocin Concentration 2 Minutes After First Intranasal Puffs
timeFrame: 2 minutes after intranasal oxytocin administration
measure: Plasma Oxytocin Concentration 5 Minutes After First Intranasal Puffs
timeFrame: 5 minutes after intranasal oxytocin administration
measure: Plasma Oxytocin Concentration 7 Minutes After First Intranasal Puffs
timeFrame: 7 minutes after intranasal oxytocin administration
measure: Plasma Oxytocin Concentration 10 Minutes After First Intranasal Puffs
timeFrame: 10 minutes after intranasal oxytocin administration
measure: Plasma Oxytocin Concentration 15 Minutes After First Intranasal Puffs
timeFrame: 15 minutes after intranasal oxytocin administration
measure: Plasma Oxytocin Concentration 20 Minutes After First Intranasal Puffs
timeFrame: 20 minutes after intranasal oxytocin administration
measure: Plasma Oxytocin Concentration 25 Minutes After First Intranasal Puffs
timeFrame: 25 minutes after intranasal oxytocin administration
measure: Plasma Oxytocin Concentration 35 Minutes After First Intranasal Puffs
timeFrame: 35 minutes after intranasal oxytocin administration
measure: Plasma Oxytocin Concentration 45 Minutes After First Intranasal Puffs
timeFrame: 45 minutes after intranasal oxytocin administration
measure: Plasma Oxytocin Concentration 60 Minutes After First Intranasal Puffs
timeFrame: 60 minutes after intranasal oxytocin administration
Secondary outcomes:
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: James C Eisenach, MD
role: PRINCIPAL_INVESTIGATOR
References: