17OHP-C Dosing Among Obese Pregnant Women

Impact of a Higher Dose on the Pharmacokinetics of 17-alpha Hydroxyprogesterone Caproate in Obese Women

Emergency data suggest 17OHP-C may be less efficacious in obese women. Since obesity is associated with lower levels of plasma 17OHP-C, the investigator hypothesize that higher doses of 17OHP-C may help to prevent spontaneous PTB among obese women. The study aims to compare the pharmacokinetics of 17 OHP-C in obese compared with non-obese women.

Study Overview

• Status: Completed
• Conditions: Premature Birth; Absorption; Chemicals
• Intervention / Treatment: Drug: 17-Hydroxyprogesterone Capronate

Detailed Description

Prospective three arm study of women with a prior spontaneous PTB. Non-obese women will receive the standard 250 mg weekly dose of 17 OHP-C while obese women will be randomly assigned to the standard (250 mg) or higher dose (500 mg). The resulting three groups will consist of:

1. Normal weight women on 250mg 17OHPC
2. Obese women on 250mg 17OHPC
3. Obese women on 500mg of 17OHPC

Initial Enrollment: Pregnant patients receiving prenatal care at one of the USF affiliated sites or Washington University in St. Louis sites who report a history of a PTB will be approached by the research nurse. The research nurse will explain the study, review inclusion/exclusion criteria with the patient, and invite interested potential study candidates to sign a medical records release so that records from the previous PTB can be reviewed. If the medical records confirm the birth of a previous PTB was of a live born singleton gestation between the gestational ages of 20 weeks and 36 weeks and 6 days then the patient will be invited to participate in the study. At that time the informed consent form will be thoroughly reviewed with the patient, and if the patient desires to enroll, the patient will provide informed consent to enroll in the study. Consecutive women with normal BMI or obese women meeting the inclusion criteria will be approached to avoid selection bias.

Randomization: will occur at the time of enrollment. The randomization will be computer generated. Randomization envelopes indicating the randomization arm will be prepared ahead of time and the next consecutive envelope will be used at time of enrollment.

Pharmacokinetic studies: Sampling schedule in order to investigate the pharmacokinetics of 250 mg 17OHP-C weekly as compared to 500 mg 17OHP-C weekly in obese women as well as 250 mg in non-obese women will be performed as follows:

- Using principles described by Caritis et al., four completed weeks of 17OHP-C therapy is required prior to sampling anticipating that steady state will be achieved by this time point.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33606
      • University of South Florida
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University in St Louis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• - Pregnant women, with a singleton gestation
• Ages 18 - 55
• Able to read and write in English and / or Spanish
• History of spontaneous PTB
• Obesity (≥ 30 kg / m2 ) vs non-obese groups (18 - 29.9 kg / m2 ) defined by first documented body mass index at an office visit
• Gestational age between 12 weeks, 0 days and 24 weeks, 6 days of gestation
• An ultrasound before 24 + 6 weeks gestation to confirm dating and to rule out major fetal anomalies
• Willing to have weekly injections at the physician's office
• The newborn will be enrolled on the mothers consent for chart review only

https://register.clinicaltrials.gov/prs/html/definitions.html?popup=true#Eligibility

Exclusion Criteria:

• - Multifetal gestation
• Known fetal anomaly
• Current progesterone treatment
• Known or suspected breast cancer, other hormone-sensitive cancer, or history of these conditions
• Current or history of thrombosis or thromboembolic disorder
• Current anticoagulation
• Undiagnosed abnormal vaginal bleeding unrelated to pregnancy
• Cholestatic jaundice of pregnancy
• Liver tumors, benign or malignant, or active liver disease
• uncontrolled hypertension (controlled hypertension is eligible)
• A seizure disorder
• Current or planned cervical cerclage
• Plan to deliver elsewhere

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: non obese; 250mg 17 OHP-C	Drug: 17-Hydroxyprogesterone Capronate; 17-Hydroxyprogesterone Capronate 250mg versus 500mg
OTHER: obese - control; 250mg 17 OHP-C	Drug: 17-Hydroxyprogesterone Capronate; 17-Hydroxyprogesterone Capronate 250mg versus 500mg
EXPERIMENTAL: obese; 500mg 17 OHP-C	Drug: 17-Hydroxyprogesterone Capronate; 17-Hydroxyprogesterone Capronate 250mg versus 500mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mean Trough Levels of 17-OHPC in the Three Groups at 20-22 Weeks, 27-29 Weeks and 34-36 Weeks.	Blood levels	From enrollment to 36 weeks of pregnancy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gestational Age at Delivery	Gestational age at delivery in weeks . Too few to dichotomize to <37, 34 and 32 weeks as previously planned.	Up to 37 weeks

Collaborators and Investigators

• Sponsor: University of South Florida
• Collaborators: Washington University School of Medicine
• Investigators: Principal Investigator: Anthony O Odibo, MD, University of South Florida

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 23, 2017
• Primary Completion (ACTUAL): June 1, 2021
• Study Completion (ACTUAL): July 14, 2021

Study Registration Dates

• First Submitted: August 28, 2017
• First Submitted That Met QC Criteria: February 7, 2018
• First Posted (ACTUAL): February 14, 2018

Study Record Updates

• Last Update Posted (ACTUAL): January 12, 2022
• Last Update Submitted That Met QC Criteria: December 17, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Estrogen Antagonists; Progestins; 17 alpha-Hydroxyprogesterone Caproate; 11-hydroxyprogesterone
• Other Study ID Numbers: 00026055

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