Study of Pharmacology of 17-OHPC in Pregnancy

Study Overview
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Brief Summary
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We are examining the pharmacology of 17-OHPC in pregnancy, specifically between the second and third trimesters.

Detailed Description
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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.

Official Title
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A Study of the Pharmacology of 17-Hydroxyprogesterone Caproate in Pregnancy

Conditions
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Pregnancy

Intervention / Treatment
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* Drug: 17-OHPC
* Procedure: Blood Draws


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Singleton gestation prior to 20 0/7 weeks gestation Planning to receive or receiving 17-OHPC (250 mg IM weekly) Previous history of preterm birth Able to give consent Exclusion Criteria: Fetal demise, anomaly, or growth restriction Hepatic or renal dysfunction Placental previa or abruptio placenta Polyhydramnios/oligohydramnios Short cervix or planned cerclage Chronic use of steroids, antiepileptics, antihypertensives, SSRS, street drugs Participation in another interventional study that influences gestational age at delivery Heparin treatment of known platelet count <100,000/mm3 (because of contraindication to intra-muscular injections)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1<br>Part 1 done after 4 weekly 17-OHPC injections completed, between 20 6/7 to 24 6/7 weeks gestation. 10 cc blood drawn pre-5th injection. 10 cc blood drawn 12 hours post-dose and 7 consecutive days. 24-hour urine collected days 4-5 within 7 days post-injection. Part 2 done 31 0/7 to 34 6/7 or at 35 0/7 weeks. 10 cc blood drawn pre weekly injection, 12 hours post-dose, and 7 consecutive days. 24-hour urine collected between days 4-5 within 7 days post-injection. A subject in whom Part 2 is performed during the last scheduled injection of 17-OHPC (at or around 35 0/7 weeks) will have the option to participate in Part 3, in which 10 cc of blood will be drawn serially over 21 days after completing Part 2. Blood will be drawn on days 9, 11, 14, 17, 20, 24, 28 after the last injection. Part 4: At the time of labor and delivery, subject will have 10cc of blood removed from a maternal peripheral vein. 10cc of blood will be collected from the placenta/umbilical cord after delivery. | Drug: 17-OHPC<br>* Intra-muscular injection of 250 mg 17-OHPC administered weekly between the second and third trimesters of pregnancy, until time of delivery.<br>* Other names: 17-alpha-hydroxyprogesterone caproate;Procedure: Blood Draws<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Area Under the Concentration vs. Time Curve in the Second and Third Trimesters of Pregnancy. | Change in the area under the concentration vs. time curve in the second and third trimesters of pregnancy. We compared AUC at each PK study visit. Measurements were obtained at 0, 1, 2, 3, 4, 5, 6, 7 days. | Second and third trimesters of pregnancy |