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

NCT ID: NCT00873886

Last Updated: 2015-09-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE1

Study Classification

INTERVENTIONAL

Study Start Date

2009-04-30

Study Completion Date

2010-09-30

Brief Summary

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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?

Detailed Description

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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.

Conditions

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Pregnancy Influenza

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Oseltamivir (Tamiflu)

Group Type EXPERIMENTAL

Oseltamivir (Tamiflu)

Intervention Type DRUG

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

Group Type OTHER

Blood Draws

Intervention Type PROCEDURE

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

Interventions

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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.

Intervention Type DRUG

Blood Draws

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

Intervention Type PROCEDURE

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

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

NIH

Sponsor Role collaborator

University of Pittsburgh

OTHER

Sponsor Role lead

Responsible Party

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Richard Beigi

Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Richard H. Beigi, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

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Magee-Womens Hospital of University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 16874296 (View on PubMed)

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. doi: 10.1093/oxfordjournals.aje.a009587.

Reference Type BACKGROUND
PMID: 9850132 (View on PubMed)

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. doi: 10.1111/j.1471-0528.2000.tb11621.x.

Reference Type BACKGROUND
PMID: 11028582 (View on PubMed)

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. doi: 10.1097/01.AOG.0000218702.92005.bb.

Reference Type BACKGROUND
PMID: 16738158 (View on PubMed)

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. doi: 10.1089/jwh.2006.15.891.

Reference Type BACKGROUND
PMID: 17087611 (View on PubMed)

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. doi: 10.1093/aje/kwj095. Epub 2006 Mar 22.

Reference Type BACKGROUND
PMID: 16554352 (View on PubMed)

ACOG Committee on Obstetric Practice. ACOG committee opinion number 305, November 2004. Influenza vaccination and treatment during pregnancy. Obstet Gynecol. 2004 Nov;104(5 Pt 1):1125-6.

Reference Type BACKGROUND
PMID: 15516422 (View on PubMed)

Garcia-Sastre A, Whitley RJ. Lessons learned from reconstructing the 1918 influenza pandemic. J Infect Dis. 2006 Nov 1;194 Suppl 2:S127-32. doi: 10.1086/507546.

Reference Type BACKGROUND
PMID: 17163385 (View on PubMed)

Webster RG, Govorkova EA. H5N1 influenza--continuing evolution and spread. N Engl J Med. 2006 Nov 23;355(21):2174-7. doi: 10.1056/NEJMp068205. No abstract available.

Reference Type BACKGROUND
PMID: 17124014 (View on PubMed)

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. doi: 10.1038/nature04017. Epub 2005 Aug 3.

Reference Type BACKGROUND
PMID: 16079797 (View on PubMed)

Moscona A. Neuraminidase inhibitors for influenza. N Engl J Med. 2005 Sep 29;353(13):1363-73. doi: 10.1056/NEJMra050740. No abstract available.

Reference Type BACKGROUND
PMID: 16192481 (View on PubMed)

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. doi: 10.2165/00002018-200326110-00004.

Reference Type BACKGROUND
PMID: 12908848 (View on PubMed)

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.)

Reference Type BACKGROUND

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.

Reference Type BACKGROUND
PMID: 8544269 (View on PubMed)

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. doi: 10.1177/00912700022009567.

Reference Type BACKGROUND
PMID: 10934667 (View on PubMed)

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. doi: 10.1093/jac/dki018.

Reference Type BACKGROUND
PMID: 15709056 (View on PubMed)

Other Identifiers

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5U10HD047905-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB #PRO07080362

Identifier Type: -

Identifier Source: org_study_id

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