A Study of the Pharmacology of Tamiflu in Pregnancy

Sponsor

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)

Overall Status

Completed

CT.gov ID

NCT01203527

Collaborator

(none)

Enrollment

Locations

67.1

Duration (Months)

15.8

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the pharmacokinetics (PK) of the anti-flu medication, Tamiflu during pregnancy and to determine to what extent pregnancy may affect the currently recommended dosage of this medication.

Condition or Disease	Intervention/Treatment	Phase
H1N1 Influenza Treatment During Pregnancy

Detailed Description

The emergence of the novel H1N1 influenza virus has raised concern among public health officials and the public alike. Although initial reports suggested that the risk of serious disease or death was less than initially feared, continued experience suggests that the disease will have a major impact on the public's health. To address this urgent public health challenge, the centers of the Obstetric-Fetal Pharmacology Research Units Network (OPRU) will recruit a total of 75 pregnant women (25 per trimester with singletons pregnancies) who are receiving oseltamivir for supposed influenza infection. When possible, we will recruit women with twin gestation to determine if fetal number affects the drugs pharmacokinetics. We do not anticipated a significant number of multi-fetal gestations (< 10) but even limited data might prove useful in this population given the tremendous change in renal drug clearance that is normally seen in this group of women. An additional 25 healthy non-pregnant women will be studied to define pregnancy- related changes in the PK of oseltamivir and the carboxylate.

We will study each woman once during therapy, performing steady state pharmacokinetic analyses. This study will be performed after 3 days of oral therapy to optimize the possibility that steady state concentrations have been achieved.

We will:

collect biological fluids (plasma and urine) to further characterize the pharmacology of the drug;
collect a check swab for DNA to allow study of the impact of single nucleotide polymorphisms on drug handing and disease expression;
develop an assay or partner with others to develop an assay for oseltamivir and the primary metabolite, oseltamivir carboxylate;
compare the pharmacokinetics of oseltamivir and its metabolite in each trimester of pregnancy to evaluate whether gestational age has an impact on the drug's pharmacokinetics;
assess the impact of fetal number on the drug's pharmacokinetics;
ask all participants about GI tolerance to the drug and any side effects they may be experiencing, especially related to mood and psychiatric well being; and
on all pregnant subjects studied, when possible, we will obtain at delivery maternal and umbilical cord blood to evaluate placental transport especially in those who deliver proximate (within 3 days) to drug treatment.

Study Design

Study Type:

Observational

Actual Enrollment :

63 participants

Observational Model:

Cohort

Official Title:

A Study of the Pharmacology of Oseltamivir (Tamiflu-Roche) in Pregnancy

Study Start Date :

Mar 1, 2007

Actual Primary Completion Date :

Oct 1, 2012

Actual Study Completion Date :

Oct 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Tamiflu use during first trimester This group will consist of twenty-five pregnant women who are being treated with Oseltamivir for clinical indications during the first trimester of their pregnancy.
Tamiflu use during second trimester This group will consist of twenty-five pregnant women who are being treated with Oseltamivir for clinical indications during the second trimester of their pregnancy.
Tamiflu use during third trimester This group will consist of twenty-five pregnant women who are being treated with Oseltamivir for clinical indications during the first trimester of their pregnancy.
Tamiflu use in non-pregnant women This group will consist of twenty-five non-pregnant healthy female volunteers who are being treated with Oseltamivir.

Outcome Measures

Primary Outcome Measures

Apparent oral clearance of oseltamivir in singletons [At the time of treatment]

Secondary Outcome Measures

Apparent oral clearance of oseltamivir in twins [At the time of treatment]
Apparent renal clearance of oseltamivir carboxylate in non-pregnant women (ancillary study) [At the time of treatment]
Concentration of oseltamivir carboxylate and oseltamivir at times 0 and 12h to ascertain steady state status [At the time of treatment]
Plasma esterase activity. (ancillary study) [At the time of treatment]
Maternal side effects -GI upset, pregnancy loss, neuropsychiatric disorder [At the time of treatment]
Maternal and cord blood oseltamivir and oseltamivir carboxylate concentrations [At delivery]

Eligibility Criteria

Criteria

Ages Eligible for Study:

14 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Taking or about to start oral oseltamivir for presumed influenza viral infection or for prophylaxis
Able to give informed consent
Pregnant female with singleton or multifetal gestation or healthy non-pregnant female (ancillary study)

Exclusion Criteria:

Unable to take medication orally
Renal failure - creatinine > 1.5
Hct <28

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Indiana University School of Medicine	Indianapolis	Indiana	United States	46202
2	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
3	University of Texas Medical Branch	Galveston	Texas	United States	77555
4	University of Washington	Seattle	Washington	United States	98195