Clinical trial NCT01203527: A Study of the Pharmacology of Tamiflu in Pregnancy
Official title: A Study of the Pharmacology of Oseltamivir (Tamiflu-Roche) in Pregnancy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: H1N1 Influenza Treatment During Pregnancy
Keywords: H1N1 influenza
Swine flu
Oseltamivir
Tamiflu
Pregnancy
Lead sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Sponsor class: NIH
First posted: 2010-09-16
Enrollment: 63
Sex: FEMALE
Minimum age (years): 14
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Pregnant and non-pregnant women

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.

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:

1. collect biological fluids (plasma and urine) to further characterize the pharmacology of the drug;
2. collect a check swab for DNA to allow study of the impact of single nucleotide polymorphisms on drug handing and disease expression;
3. develop an assay or partner with others to develop an assay for oseltamivir and the primary metabolite, oseltamivir carboxylate;
4. 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;
5. assess the impact of fetal number on the drug's pharmacokinetics;
6. 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
7. 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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

1. Unable to take medication orally
2. Renal failure - creatinine \> 1.5
3. Hct \<28

Primary outcomes:
measure: Apparent oral clearance of oseltamivir in singletons
timeFrame: At the time of treatment
Secondary outcomes:
measure: Apparent oral clearance of oseltamivir in twins
timeFrame: At the time of treatment
measure: Apparent renal clearance of oseltamivir carboxylate in non-pregnant women (ancillary study)
timeFrame: At the time of treatment
measure: Concentration of oseltamivir carboxylate and oseltamivir at times 0 and 12h to ascertain steady state status
timeFrame: At the time of treatment
measure: Plasma esterase activity. (ancillary study)
timeFrame: At the time of treatment
measure: Maternal side effects -GI upset, pregnancy loss, neuropsychiatric disorder
timeFrame: At the time of treatment
measure: Maternal and cord blood oseltamivir and oseltamivir carboxylate concentrations
timeFrame: At delivery
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: University of Pittsburgh
name: Richard Beigi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh
name: Steve Caritis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh
name: Raman Venkataramanan, PhD
role: PRINCIPAL_INVESTIGATOR
References: