A Study of the Pharmacology of Tamiflu in Pregnancy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT01203527
First received: September 15, 2010
Last updated: October 8, 2013
Last verified: August 2013
  Purpose

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
H1N1 Influenza Treatment During Pregnancy

Study Type: Observational
Study Design: Observational Model: Cohort
Official Title: A Study of the Pharmacology of Oseltamivir (Tamiflu-Roche) in Pregnancy

Resource links provided by NLM:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:
  • Apparent oral clearance of oseltamivir in singletons [ Time Frame: At the time of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Apparent oral clearance of oseltamivir in twins [ Time Frame: At the time of treatment ] [ Designated as safety issue: No ]
  • Apparent renal clearance of oseltamivir carboxylate in non-pregnant women (ancillary study) [ Time Frame: At the time of treatment ] [ Designated as safety issue: No ]
  • Concentration of oseltamivir carboxylate and oseltamivir at times 0 and 12h to ascertain steady state status [ Time Frame: At the time of treatment ] [ Designated as safety issue: No ]
  • Plasma esterase activity. (ancillary study) [ Time Frame: At the time of treatment ] [ Designated as safety issue: No ]
  • Maternal side effects -GI upset, pregnancy loss, neuropsychiatric disorder [ Time Frame: At the time of treatment ] [ Designated as safety issue: No ]
  • Maternal and cord blood oseltamivir and oseltamivir carboxylate concentrations [ Time Frame: At delivery ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Blood and urine


Enrollment: 63
Study Start Date: March 2007
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts
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.

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

Ages Eligible for Study:   14 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Pregnant and non-pregnant women

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01203527

Locations
United States, Indiana
Indiana University School of Medicine
Indianapolis, Indiana, United States, 46202
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
University of Texas Medical Branch
Galveston, Texas, United States, 77555
United States, Washington
University of Washington
Seattle, Washington, United States, 98195
Sponsors and Collaborators
Investigators
Principal Investigator: Richard Beigi, MD University of Pittsburgh
Principal Investigator: Steve Caritis, MD University of Pittsburgh
Principal Investigator: Raman Venkataramanan, PhD University of Pittsburgh
  More Information

No publications provided

Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier: NCT01203527     History of Changes
Other Study ID Numbers: OPRU Tamiflu
Study First Received: September 15, 2010
Last Updated: October 8, 2013
Health Authority: United States: Federal Government

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
H1N1 influenza
Swine flu
Oseltamivir
Tamiflu
Pregnancy

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Oseltamivir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 23, 2014