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

This study has been withdrawn prior to enrollment.
(We will focus on our other research studies that involve Tamiflu. Zero subjects were enrolled in this study.)
Sponsor:
Collaborator:
Information provided by:
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00873886
First received: April 1, 2009
Last updated: November 2, 2010
Last verified: November 2010
  Purpose

The primary research question of this study is: Does the pharmacokinetics of oseltamivir after a single oral dose differ between the pregnant and non-pregnant women?


Condition Intervention Phase
Pregnancy
Influenza
Drug: Oseltamivir (Tamiflu)
Procedure: Blood Draws
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: A Study of the Pharmacology of Oseltamivir (Tamiflu) in Pregnancy

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Change in the area under the concentration vs. time curve (AUC 0-7 d) in the first and second trimesters of pregnancy with comparisons to the post-termination non-pregnant follow-up data on these enrollees and historical non-pregnant data. [ Time Frame: Less than 9 weeks for subjects planning termination; up to 5 months for subjects enrolled during their 3rd trimester. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Non-compartmental model analysis for Cmax, Tmax, Cl/F, Clr,V/F, MRT and t ½. [ Time Frame: Less than 9 weeks for subjects planning termination; up to 5 months for subjects enrolled during their 3rd trimester. ] [ Designated as safety issue: No ]
  • Plasma concentrations of oseltamivir after single-dosing. [ Time Frame: Less than 9 weeks for subjects planning termination; up to 5 months for subjects enrolled during their 3rd trimester. ] [ Designated as safety issue: No ]
  • Evaluation of carboxy-esterase levels and activity in all trimesters of pregnancy with comparison to the post-partum internal controls. [ Time Frame: Less than 9 weeks for subjects planning termination; up to 5 months for subjects enrolled during their 3rd trimester. ] [ Designated as safety issue: No ]
  • Tolerance (side effect profile) of single-dose oseltamivir in pregnancy. [ Time Frame: Less than 9 weeks for subjects planning termination; up to 5 months for subjects enrolled during their 3rd trimester. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 39
Study Start Date: April 2009
Estimated Study Completion Date: September 2010
Estimated Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oseltamivir (Tamiflu) Drug: Oseltamivir (Tamiflu)

The following procedures will be performed on two occasions: once at least three days prior to the scheduled pregnancy termination procedure and again about eight weeks after the termination procedure.

A) Subject will take 75 mg of oseltamivir pill by mouth

B) Multiple blood draws (1 teaspoon each) over the next 48 hours after taking oseltamivir. Urine samples also will be collected.

Esterase Procedure: Blood Draws
Two blood draws (1 teaspoon each) will be performed: once during third trimester of pregnancy and again about eight weeks after delivery.

Detailed Description:

With the pending threat of pandemic avian influenza, the disproportionate morbidity and mortality documented in previous 20th century pandemics among pregnant women, and the lack of any data for use of these vital antiviral drugs in pregnancy, study of the pharmacology of oseltamivir in pregnancy is imperative. If and when the next pandemic occurs, a better understanding of this drug's safety and pharmacologic profiles for use in pregnancy is critical given the fact that it will be used in this vulnerable patient population.

This is a pilot study of the use of oseltamivir in pregnancy. This data will be combined with data from the parallel Pediatric Pharmacology Research Unit (PPRU) studies to put together a portfolio for use in understudied populations. This will allow for a re-thinking of the current status and potentially allow for small trials to be performed with patients who are suffering from influenza in pregnancy, to assess efficacy. The relevance with the pandemic strain and its corresponding Minimum Inhibitory Concentration (MIC) may have direct implications for dosing in pregnancy if lower levels of drug are documented. In addition, depending on the findings from the esterase component of the investigation, future investigation into mechanistic bases for changes in enzyme activity are possible.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • For Oseltamivir (Tamiflu) arm:
  • Singleton gestation prior to 24 0/7 weeks gestation
  • Planning to undergo a termination procedure for the incident pregnancy
  • Willingness to take the single-dose medication and to follow study procedures
  • Able to undergo informed consent.
  • For Esterase arm:
  • Singleton gestation greater than 32 completed weeks and less than 40 completed weeks of gestation
  • Absence of severe pregnancy complication that could affect body volume and or metabolism (i.e., preeclampsia, renal dysfunction, hepatic dysfunction [defined as serum creatinine clearance of < 30 ml/min or a known ALT/AST> 2x facility normal value], etc.)
  • Willingness to follow study procedures
  • Able to undergo informed consent
  • The use of medications that may affect renal metabolism is not a contraindication to participation since these subjects are only undergoing PK sampling.

Exclusion Criteria:

  • For Oseltamivir (Tamiflu) arm:
  • Known current in utero fetal death
  • Significant medical history and/or medication use as determined by the investigator that has the potential to affect results of the study or put the patient at risk from the single-dosing
  • Known hypersensitivity to the components of the study drug
  • Known hepatic or renal dysfunction (defined as serum creatinine clearance of < 30 ml/min or a known ALT/AST> 2x facility normal value)
  • Chronic use of street drugs (obtained via subject interview and/or medical history)
  • Participation in any other concurrent interventional study.
  • We will ask if they have a history of depression in the past requiring treatment or if they are currently actively depressed. If either of these questions yields a positive response, we will not consider the patient eligible and will not enroll the subject.
  • For Esterase arm:
  • Known current in utero fetal death
  • Significant medical history as determined by the investigator to potentially affect results of the study
  • Chronic use of street drugs (obtained via subject interview and/or medical history
  • Participation in any other concurrent interventional study.
  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: NCT00873886

Locations
United States, Pennsylvania
Magee-Womens Hospital of University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: Richard H. Beigi, MD University of Pittsburgh
  More Information

Publications:
Influenza vaccination and treatment during pregnancy. ACOG Committee Opinion No. 305. American College of Obstetricians and Gynecologists. Obstet Gynecol 2004;104:1125-6.
Moscona A. Neuraminidase inhibitors for influenza. N Engl J Med 2005;353:1363-73.

Responsible Party: Richard H. Beigi, MD, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00873886     History of Changes
Other Study ID Numbers: IRB #PRO07080362, NIH Grant #5U10HD047905-02
Study First Received: April 1, 2009
Last Updated: November 2, 2010
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Oseltamivir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014