Study of Pharmacology of 17-OHPC in Pregnancy
We are examining the pharmacology of 17-OHPC in pregnancy, specifically between the second and third trimesters.
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
|Official Title:||A Study of the Pharmacology of 17-Hydroxyprogesterone Caproate in Pregnancy|
- Change in the area under the concentration vs. time curve in the second and third trimesters of pregnancy. [ Time Frame: Second and third trimesters of pregnancy ] [ Designated as safety issue: No ]
- Maternal Secondary Outcomes include: non-compartmental model analysis for Cmax, Tmax, Cl/F, Clr,V/F, MRT and t ½; [ Time Frame: Second and third trimesters of pregnancy ] [ Designated as safety issue: No ]
- plasma concentrations of 17-OHPC prior to each injection; metabolites of 17-OHPC in maternal blood and urine; genotype of 17-OHPC metabolizing enzymes; CRP, CRH, and other progestational biomarkers; plasma progesterone, 17 hydroxyprogesterone, estradiol. [ Time Frame: Second and third trimesters of pregnancy ] [ Designated as safety issue: No ]
- Fetal and Neonatal Outcomes include: cord 17-OHPC and metabolite concentrations; maternal:fetal drug ratios [ Time Frame: Post-partum ] [ Designated as safety issue: No ]
|Study Start Date:||March 2006|
|Primary Completion Date:||April 2008 (Final data collection date for primary outcome measure)|
Experimental: Part 1
Part 1 of the study can be done after 4 weekly injections have been completed (so that plasma concentrations will be at or near steady state) and the fifth injection is about to be given; hence Part 1 will be done at a gestation of 20 6/7 to 24 6/7 weeks. Prior to receiving the fifth weekly injection of 17-OHPC, 10 cc of blood will be drawn from a vein in subject's arm. After the fifth injection, 10 cc of blood will be drawn from a vein in subject's arm 12 hours post-dose and daily for seven consecutive days (subjects already enrolled in the study will be asked to sign a new consent form in order to obtain the additional sample at 12 hours post-dose). Each daily collection should occur at similar times of the day, within 4 hours of the injection time of the fifth injection. In addition to the blood draws, subject will be asked to collect a 24-hour urine between days 4 and 5 of the 7-day post-injection period.
Intra-muscular injection of 250 mg 17-OHPC administered weekly between the second and third trimesters of pregnancy, until time of delivery.Procedure: Blood Draws
10 cc of blood will be drawn prior to the fifth weekly administration of 17-OHPC during second trimester of pregnancy, and then once daily for seven consecutive days post-dose. 10 cc of blood also will be drawn prior to weekly administration of 17-OHPC from sixth weekly dose in the second trimester until the last scheduled dose in the third trimester. Prior to this last scheduled dose, 10 cc of blood will be drawn, as well as once daily for seven consecutive days post-dose.
The recently completed trial by the National Institute of Child Health and Human Development (NICHD)-sponsored Maternal-Fetal Medicine Units (MFMU) Network has demonstrated that intramuscular 17-alpha-hydroxyprogesterone caproate (17-OHPC) substantially reduces the rate of preterm birth in women at high risk for preterm delivery because of a prior spontaneous preterm birth. No other strategy or treatment for prevention of preterm birth has proven to be effective. Consequently, the American College of Obstetricians and Gynecologists has cautiously supported this treatment but points out that much more information about this therapy and alternative therapies is required. Although a large body of evidence exists about the safety of this treatment, almost nothing is known about the pharmacology of this agent, especially in pregnancy. The purpose of this study is to define the pharmacology of 17-hydroxyprogesterone caproate in pregnancy. This protocol will focus on pharmacokinetics and placental transport and provide preliminary data on the pharmacoepidemiology of 17-OHPC. The primary research question of this study is: Do the pharmacokinetics of 17-OHPC as represented by area under the concentration vs. time curve after IM injection of 250 mg 17-OHPC differ between the second and third trimesters of pregnancy? We will obtain blood samples prior to and daily for one week after injection of 17-OHPC (8 samples total) for each of two parts of the study, with an optional third part for eligible subjects. Additionally, blood samples will be collected prior to each weekly injection of the study drug and at time of delivery. Approximately 60 subjects (ages 18-45) will be accrued at one of the Obstetrical Fetal Pharmacology Research Units (OPRU) Network sites, with 15 at Magee-Womens Hospital of the University of Pittsburgh Medical Center. Study treatment will be administered until delivery. The total duration of this multi-center study is 2-3 years.
|United States, District of Columbia|
|Washington, District of Columbia, United States, 20010|
|United States, Pennsylvania|
|Magee-Womens Hospital of University of Pittsburgh Medical Center|
|Pittsburgh, Pennsylvania, United States, 15213|
|United States, Texas|
|University of Texas|
|Galveston, Texas, United States, 77555|
|United States, Washington|
|University of Washington|
|Seattle, Washington, United States, 98195|
|Principal Investigator:||Steve N. Caritis, MD||University of Pittsburgh|