Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Study of Pharmacology of 17-OHPC in Pregnancy

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00409825
First received: December 8, 2006
Last updated: July 1, 2014
Last verified: July 2014

December 8, 2006
July 1, 2014
March 2006
April 2008   (final data collection date for primary outcome measure)
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 ]
Change in the area under the concentration vs. time curve in the second and third trimesters of pregnancy.
Complete list of historical versions of study NCT00409825 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Maternal Secondary Outcomes include: non-compartmental model analysis for Cmax, Tmax, Cl/F, Clr,V/F, MRT and t ½;
  • 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.
  • Fetal and Neonatal Outcomes include: cord 17-OHPC and metabolite concentrations; maternal:fetal drug ratios
Not Provided
Not Provided
 
Study of Pharmacology of 17-OHPC in Pregnancy
A Study of the Pharmacology of 17-Hydroxyprogesterone Caproate in Pregnancy

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

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.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Pregnancy
  • Drug: 17-OHPC
    Intra-muscular injection of 250 mg 17-OHPC administered weekly between the second and third trimesters of pregnancy, until time of delivery.
    Other Name: 17-alpha-hydroxyprogesterone caproate
  • 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.
Experimental: Part 1
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 4, 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 3: 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.
Interventions:
  • Drug: 17-OHPC
  • Procedure: Blood Draws

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
61
February 2014
April 2008   (final data collection date for primary outcome measure)

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)
Female
18 Years to 45 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00409825
IRB #0603056, 5U10HD047905-02
Yes
University of Pittsburgh
University of Pittsburgh
  • National Institutes of Health (NIH)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Principal Investigator: Steve N. Caritis, MD University of Pittsburgh
University of Pittsburgh
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP