Oxytocin Pharmacokinetics and Pharmacodynamics

NCT05488457 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IRB24-0480
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

Brief Summary

Oxytocin is the first-line drug to promote contraction of the uterus and prevent atony immediately after delivery. Nonetheless, unpredictable uterine atony refractory to oxytocin affects roughly 250,000 parturients annually in the U.S. and rates are increasing. This two-part study will measure the action of oxytocin at cesarean delivery. The first part will measure the pharmacokinetics of a single intravenous (IV) dose of deuterium-labeled oxytocin. The second part will measure the pharmacodynamics of all plasma oxytocin to see how concentrations correspond to the contractile effect on the uterus. After delivery of the fetus, study subjects will receive a bolus of IV deuterated oxytocin followed by an unlabeled oxytocin infusion. Venous blood samples drawn at multiple time points (within 1 hour after delivery) will be analyzed for plasma concentrations of labeled and unlabeled (endogenous + exogenous infused) oxytocin over time. Plasma concentrations will be compared with 0-10 uterine tone scores measuring uterine contraction strength, to describe the concentration-effect relationship. The goal of this study is to define both the pharmacokinetics and pharmacodynamics of oxytocin in parturients to help identify the cause(s) of failed first-line oxytocin therapy.

Conditions

Post Partum Hemorrhage; Cesarean Section Complications; Blood Loss

Keywords

Oxytocin; pharmacokinetics and Pharmacodynamics; Uterine Tone; Postpartum; Elective C-Section; Parturients

Outcome Measures

Primary Outcomes (20)

• Baseline plasma concentrations of deuterated oxytocin

  The plasma concentration of deuterium labelled oxytocin at baseline

  Intraoperatively (prior to delivery)

• Plasma concentrations of deuterated oxytocin at 1 minute

  The plasma concentration of deuterium labelled oxytocin at 1 minute post-study drug

  Intraoperatively (1 minute following study drug administration)

• Plasma concentrations of deuterated oxytocin at 2.5 minutes

  The plasma concentration of deuterium labelled oxytocin at 2.5 minutes post-study drug

  Intraoperatively (2.5 minutes following study drug administration)

• Plasma concentrations of deuterated oxytocin at 5 minutes

  The plasma concentration of deuterium labelled oxytocin at 5 minutes post-study drug

  Intraoperatively (5 minutes following study drug administration)

• Plasma concentrations of deuterated oxytocin at 10 minutes

  The plasma concentration of deuterium labelled oxytocin at 10 minutes post-study drug

  Intraoperatively (10 minutes following study drug administration)

• Plasma concentrations of deuterated oxytocin at 15 minutes

  The plasma concentration of deuterium labelled oxytocin at 15 minutes post-study drug

  Intraoperatively (15 minutes following study drug administration)

• Plasma concentrations of deuterated oxytocin at 20 minutes

  The plasma concentration of deuterium labelled oxytocin at 20 minutes post-study drug

  Intraoperatively (20 minutes following study drug administration)

• Plasma concentrations of deuterated oxytocin at 30 minutes

  The plasma concentration of deuterium labelled oxytocin at 30 minutes post-study drug

  Intraoperatively (30 minutes following study drug administration)

• Plasma concentrations of deuterated oxytocin at 45 minutes

  The plasma concentration of deuterium labelled oxytocin at 45 minutes post-study drug

  Intraoperatively (45 minutes following study drug administration)

• Plasma concentrations of deuterated oxytocin at 60 minutes

  The plasma concentration of deuterium labelled oxytocin at 60 minutes post-study drug

  Intraoperatively (60 minutes following study drug administration)

• 0-10 Uterine Tone Score

  Uterine tone will be ranked by the obstetrician on a 0-10 scale by palpation of the uterus. A score of 0 will represent 'no tone' and a score of 10 will represent 'perfect tone'. The relationship between plasma concentrations and clinical effect will be determined for pharmacodynamic modeling.

  Intraoperatively (at the time of study drug administration)

• 0-10 Uterine Tone Score

  Uterine tone ranked by the obstetrician on a 0-10 scale by palpation of the uterus. A score of 0 will represent 'no tone' and a score of 10 will represent 'perfect tone'. The relationship between plasma concentrations and clinical effect will be determined for pharmacodynamic modeling.

  Intraoperatively (1 minute following study drug administration)

• 0-10 Uterine Tone Score

  Uterine tone ranked by the obstetrician on a 0-10 scale by palpation of the uterus. A score of 0 will represent 'no tone' and a score of 10 will represent 'perfect tone'. The relationship between plasma concentrations and clinical effect will be determined for pharmacodynamic modeling.

  Intraoperatively (2.5 minutes following study drug administration)

• 0-10 Uterine Tone Score

  Uterine tone ranked by the obstetrician on a 0-10 scale by palpation of the uterus. A score of 0 will represent 'no tone' and a score of 10 will represent 'perfect tone'. The relationship between plasma concentrations and clinical effect will be determined for pharmacodynamic modeling.

  Intraoperatively (5 minutes following study drug administration)

• 0-10 Uterine Tone Score

  Uterine tone ranked by the obstetrician on a 0-10 scale by palpation of the uterus. A score of 0 will represent 'no tone' and a score of 10 will represent 'perfect tone'. The relationship between plasma concentrations and clinical effect will be determined for pharmacodynamic modeling.

  Intraoperatively (10 minutes following study drug administration)

• 0-10 Uterine Tone Score

  Uterine tone ranked by the obstetrician on a 0-10 scale by palpation of the uterus. A score of 0 will represent 'no tone' and a score of 10 will represent 'perfect tone'. The relationship between plasma concentrations and clinical effect will be determined for pharmacodynamic modeling.

  Intraoperatively (15 minutes following study drug administration)

• 0-10 Uterine Tone Score

  Uterine tone ranked by the obstetrician on a 0-10 scale by palpation of the uterus. A score of 0 will represent 'no tone' and a score of 10 will represent 'perfect tone'. The relationship between plasma concentrations and clinical effect will be determined for pharmacodynamic modeling.

  Intraoperatively (20 minutes following study drug administration)

• 0-10 Uterine Tone Score

  Uterine tone ranked by the obstetrician on a 0-10 scale by palpation of the uterus. A score of 0 will represent 'no tone' and a score of 10 will represent 'perfect tone'. The relationship between plasma concentrations and clinical effect will be determined for pharmacodynamic modeling.

  Intraoperatively (30 minutes following study drug administration)

• 0-10 Uterine Tone Score

  Uterine tone ranked by the obstetrician on a 0-10 scale by palpation of the uterus. A score of 0 will represent 'no tone' and a score of 10 will represent 'perfect tone'. The relationship between plasma concentrations and clinical effect will be determined for pharmacodynamic modeling.

  Intraoperatively (45 minutes following study drug administration)

• 0-10 Uterine Tone Score

  Uterine tone ranked by the obstetrician on a 0-10 scale by palpation of the uterus. A score of 0 will represent 'no tone' and a score of 10 will represent 'perfect tone'. The relationship between plasma concentrations and clinical effect will be determined for pharmacodynamic modeling.

  Intraoperatively (60 minutes following study drug administration)

Study Arms (1)

Oxytocin PK/PD Arm

EXPERIMENTAL

Eligible subjects will receive a single, 1 IU bolus of deuterated oxytocin (d5OT) intra-operatively, followed by an infusion of standard therapeutic d0 oxytocin immediately after placental delivery.

Drug: deuterated oxytocin (d5OT)

Interventions

deuterated oxytocin (d5OT) DRUG

Subjects will receive a 1 IU bolus of deuterated oxytocin (d5OT) intraoperatively during their nonemergent cesarean delivery.

Also known as: Deuterium-labeled oxytocin

Oxytocin PK/PD Arm

Eligibility Criteria

• Age: 18 Years - 50 Years
• Gender Eligibility Details: Women undergoing non-emergent cesarean delivery
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• years old
• intrauterine pregnancy
• term (\>39 weeks gestation or 37-39 weeks gestation with fetal or maternal medical indication for delivery) pregnancy
• non-emergent (scheduled or unscheduled) cesarean delivery

You may not qualify if:

• allergy or contraindication to oxytocin
• inability to provide informed consent

Sponsors & Collaborators

• University of Chicago: lead
• Stanford University: collaborator

Study Sites (2)

Stanford University

Stanford, California, 94305, United States

NOT YET RECRUITING

University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

MeSH Terms

Conditions

Postpartum Hemorrhage; Hemorrhage

Condition Hierarchy (Ancestors)

Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Puerperal Disorders; Uterine Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Naida M Cole, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Naida M Cole, MD

CONTACT

773-702-6700; nmcole@bsd.uchicago.edu

Somayeh Mohammadi

CONTACT

17738343274; mohammadis@bsd.uchicago.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All subjects will receive a 1 IU bolus of deuterated oxytocin (d5OT) intraoperatively during their cesarean delivery.

Study Record Dates

• First Submitted: July 19, 2022
• First Posted: August 4, 2022
• Study Start: January 1, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: October 3, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)