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

Information source: University of Pittsburgh
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Pregnancy; Influenza

Intervention: Oseltamivir (Tamiflu) (Drug); Blood Draws (Procedure)

Phase: Phase 1

Status: Withdrawn

Sponsored by: University of Pittsburgh

Official(s) and/or principal investigator(s):
Richard H. Beigi, MD, Principal Investigator, Affiliation: University of Pittsburgh

Summary

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?

Clinical Details

Official title: A Study of the Pharmacology of Oseltamivir (Tamiflu) in Pregnancy

Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Primary outcome: 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.

Secondary outcome:

Non-compartmental model analysis for Cmax, Tmax, Cl/F, Clr,V/F, MRT and t ½.

Plasma concentrations of oseltamivir after single-dosing.

Evaluation of carboxy-esterase levels and activity in all trimesters of pregnancy with comparison to the post-partum internal controls.

Tolerance (side effect profile) of single-dose oseltamivir in pregnancy.

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

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Female.

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.

Locations and Contacts

Magee-Womens Hospital of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, United States
Additional Information

Related publications:

Advisory Committee on Immunization Practices, Smith NM, Bresee JS, Shay DK, Uyeki TM, Cox NJ, Strikas RA. Prevention and Control of Influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006 Jul 28;55(RR-10):1-42. Erratum in: MMWR Morb Mortal Wkly Rep. 2006 Jul 28;55(29):800.

Neuzil KM, Reed GW, Mitchel EF, Simonsen L, Griffin MR. Impact of influenza on acute cardiopulmonary hospitalizations in pregnant women. Am J Epidemiol. 1998 Dec 1;148(11):1094-102.

Irving WL, James DK, Stephenson T, Laing P, Jameson C, Oxford JS, Chakraverty P, Brown DW, Boon AC, Zambon MC. Influenza virus infection in the second and third trimesters of pregnancy: a clinical and seroepidemiological study. BJOG. 2000 Oct;107(10):1282-9.

Cox S, Posner SF, McPheeters M, Jamieson DJ, Kourtis AP, Meikle S. Hospitalizations with respiratory illness among pregnant women during influenza season. Obstet Gynecol. 2006 Jun;107(6):1315-22.

Cox S, Posner SF, McPheeters M, Jamieson DJ, Kourtis AP, Meikle S. Influenza and pregnant women: hospitalization burden, United States, 1998-2002. J Womens Health (Larchmt). 2006 Oct;15(8):891-3.

Lindsay L, Jackson LA, Savitz DA, Weber DJ, Koch GG, Kong L, Guess HA. Community influenza activity and risk of acute influenza-like illness episodes among healthy unvaccinated pregnant and postpartum women. Am J Epidemiol. 2006 May 1;163(9):838-48. Epub 2006 Mar 22.

Influenza vaccination and treatment during pregnancy. ACOG Committee Opinion No. 305. American College of Obstetricians and Gynecologists. Obstet Gynecol 2004;104:1125-6.

Garcia-Sastre A, Whitley RJ. Lessons learned from reconstructing the 1918 influenza pandemic. J Infect Dis. 2006 Nov 1;194 Suppl 2:S127-32.

Webster RG, Govorkova EA. H5N1 influenza--continuing evolution and spread. N Engl J Med. 2006 Nov 23;355(21):2174-7.

Ferguson NM, Cummings DA, Cauchemez S, Fraser C, Riley S, Meeyai A, Iamsirithaworn S, Burke DS. Strategies for containing an emerging influenza pandemic in Southeast Asia. Nature. 2005 Sep 8;437(7056):209-14. Epub 2005 Aug 3.

Moscona A. Neuraminidase inhibitors for influenza. N Engl J Med. 2005 Sep 29;353(13):1363-73. Review.

Dutkowski R, Thakrar B, Froehlich E, Suter P, Oo C, Ward P. Safety and pharmacology of oseltamivir in clinical use. Drug Saf. 2003;26(11):787-801. Review.

Health Sciences Authority. Product Safety Alert: new preclinical findings on Oseltamivir. March 2004. (Accessed November 27, 2006 at: http://www.hsa.gov.sg/docs/safetyalert_oseltamivir_March04.pdf.)

Hayden FG, Treanor JJ, Betts RF, Lobo M, Esinhart JD, Hussey EK. Safety and efficacy of the neuraminidase inhibitor GG167 in experimental human influenza. JAMA. 1996 Jan 24-31;275(4):295-9.

Massarella JW, He GZ, Dorr A, Nieforth K, Ward P, Brown A. The pharmacokinetics and tolerability of the oral neuraminidase inhibitor oseltamivir (Ro 64-0796/GS4104) in healthy adult and elderly volunteers. J Clin Pharmacol. 2000 Aug;40(8):836-43.

Ward P, Small I, Smith J, Suter P, Dutkowski R. Oseltamivir (Tamiflu) and its potential for use in the event of an influenza pandemic. J Antimicrob Chemother. 2005 Feb;55 Suppl 1:i5-i21. Review.

Starting date: April 2009
Last updated: November 2, 2010

Page last updated: August 23, 2015

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