Pharmacokinetics of Antiretroviral Agents in HIV-infected Pregnant Women. (PANNA)

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ClinicalTrials.gov Identifier: NCT00825929

Recruitment Status : Recruiting

First Posted : January 21, 2009

Last Update Posted : January 23, 2019

See Contacts and Locations

Sponsor:

Collaborators:

PENTA Foundation

Merck Sharp & Dohme Corp.

Bristol-Myers Squibb

Janssen Pharmaceutica

ViiV Healthcare

Information provided by (Responsible Party):

Radboud University

Study Description

Brief Summary:

Due to the potential for pregnancy-induced changes in the pharmacokinetics of medication, one cannot assume that the currently licensed doses of the medication to be tested under this protocol lead to adequate exposure in an HIV-infected pregnant woman. For the agents under study no or limited pharmacokinetic data during pregnancy are available. As the changes in pharmacokinetics during pregnancy are most prominent in the third trimester a pharmacokinetic curve will be recorded in the third trimester after attaining steady state.

Condition or disease
HIV Infections

Detailed Description:

The following agents will be studied:

Etravirine, Intelence, TMC125; Emtricitabine, Emtriva or FTC; Tenofovir, Viread, TDF; Atazanavir, Reyataz; Fosamprenavir, Telzir, FPV; Darunavir, Prezista, TMC114; Tipranavir, Aptivus, TPV; Indinavir, Crixivan; abacavir; raltegravir, Isentress; Enfuvirtide, Fuzeon; Maraviroc, Celsentri; dolutegravir; elvitegravir/cobicistat; rilpivirine, TAF, darunavir/cobicistat

Study Design

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Study Type :	Observational
Estimated Enrollment :	176 participants
Observational Model:	Case-Crossover
Time Perspective:	Prospective
Official Title:	Study on Pharmacokinetics of Newly Developed ANtiretroviral Agents in HIV-infected pregNAnt Women (PANNA)
Study Start Date :	February 2009
Estimated Primary Completion Date :	December 2020
Estimated Study Completion Date :	December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

U.S. FDA Resources

Groups and Cohorts

Group/Cohort
1 Treated with one of the antiretroviral agents under study, PK parameters during pregnancy will be compared with PK parameters after pregnancy (within the same woman)

Outcome Measures

Primary Outcome Measures :

Plasma concentrations of the compounds during pregnancy compared to the concentrations after delivery [ Time Frame: PK curve in Week 33 of pregnancy and 4-6 weeks after delivery ]

Secondary Outcome Measures :

Pharmacokinetics in the neonate, in case of post-exposure prophylaxis with one of the agents under study. [ Time Frame: Week 1, 3 and between 4 and 6 ]
Safety of antiretrovirals during pregnancy [ Time Frame: GA Week 33 until end of trial ]
viral load response and prevention of mother to child transmission of the virus [ Time Frame: GA Week 3 and at delivery ]

Biospecimen Retention: Samples Without DNA

Plasma samples will be collected in Week 33 of the pregnancy and at 4-6 weeks after delivery. At the following time points samples will be collected: T=0 (prior to dosing), and T=1, 2, 3, 4, 6, 8, 12 and 24h (24h sample only in case of QD regimen) post-dosing (8 or 9 samples).

In case the infant needs post-exposure prophylaxis with at least one of the agents sparse PK sampling is optional.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

HIV-infected pregnant women using at least one of the following antiretroverial agents: Etravirine, Intelence, TMC125; Emtricitabine, Emtriva or FTC; Tenofovir, Viread, TDF; Atazanavir, Reyataz; Fosamprenavir, Telzir, FPV; Darunavir, Prezista, TMC114; Tipranavir, Aptivus, TPV; Indinavir, Crixivan; Raltegravir, Isentress; Enfuvirtide, Fuzeon; Maraviroc, Celsentri; Abacavir; Rilpivirine

Criteria

Inclusion Criteria:

HIV-infected as documented by positive HIV antibody test and confirmed by Western Blot.
Subject is at least 18 years of age at screening.
Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
Treated with an HAART regimen containing at least one agent which is mentioned in Appendix 1 of the protocol; this agent has been taken for at least 2 weeks before the day of first PK curve evaluation.
Duration of pregnancy not longer than 33 weeks at the day of screening
Subject is able to adhere to food intake recommendations.

Exclusion Criteria:

Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
Inability to understand the nature and extent of the study and the procedures required.
Presence of grade III/IV anemia (i.e. Hb <4.6 mmol/L or <7.4 g/dL)

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00825929

Contacts

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Contact: David M Burger, PharmD PhD	++31 24 3616405	dadvid.burger@radboudumc.nl
Contact: Angela Colbers, MSc	++31 24 3616405	angela.colbers@radboudumc.nl

Locations

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Belgium
Saint-Pierre University Hospital; Department of Infectious Diseases	Recruiting
Brussels, Belgium
Contact: D Konopnicki
Principal Investigator: D Konopnicki, MD
Germany
CHARITÉ Berlin	Recruiting
Berlin, Germany
Contact: Katharina von Weizsaecker katharina.weizsaecker@charite.de
Principal Investigator: Katharina von Weizsaecker, MD
University of Bonn	Recruiting
Bonn, Germany
Principal Investigator: Juergen Rockstroh, MD, PhD
University of Cologne	Recruiting
Cologne, Germany
Principal Investigator: Gerd Faetkenheuer, MD, PhD
Johann Wolfgang Goethe-Universität	Recruiting
Frankfurt am Main, Germany
Contact: Anette Haberl Annette.Haberl@hivcenter.de
Principal Investigator: Annette Haberl, MD
University München	Recruiting
München, Germany
Contact: Irene Alba
Principal Investigator: B Kost, MD
Ireland
Mater Hospital and UCD	Recruiting
Dublin, Ireland
Contact: John Lambert jlambert@mater.ie
Principal Investigator: John Lambert, MD
St James's Hospital Dublin	Recruiting
Dublin, Ireland
Contact: Fiona Lyons FLyons@STJAMES.IE
Principal Investigator: Fiona Lyons, MD
Italy
IRCSS	Recruiting
Rome, Italy
Principal Investigator: A Antinori, MD
Netherlands
AMC	Not yet recruiting
Amsterdam, Netherlands
Contact: Jeannine Nellen, MD, PhD
Principal Investigator: Jeannine Nellen, MD, PhD
AMC	Recruiting
Amsterdam, Netherlands
Contact: Jeannine Nellen
Principal Investigator: Jeannine Nellen
Radboud University Nijmegen Medical Centre	Recruiting
Nijmegen, Netherlands
Principal Investigator: Andre van der Ven, Md. PhD
Erasmus Medical Center Rotterdam	Recruiting
Rotterdam, Netherlands
Principal Investigator: Ineke van der Ende, MD, PhD
St Elisabeth hospital	Recruiting
Tilburg, Netherlands
Contact: Marjo van Kasteren
Principal Investigator: Marjo van Kasteren
St Elisabeth Ziekenhuis	Recruiting
Tilburg, Netherlands
Contact: M van Kasteren
Principal Investigator: M van Kasteren, MD
Spain
Hospital Universitari Germans Trias i Pujol, Badalona	Recruiting
Badalona, Spain
Principal Investigator: Jose Molto, MD, PhD
Hospital Universitario Virgen de las Nieves Granada; Médico Adjunto del Servicio de Medicina Interna	Recruiting
Granada, Spain
Contact: Carmen Hidalgo Tenori chidalgo72@hotmail.com
Principal Investigator: Carmen Hidalgo Tenori, MD
United Kingdom
Brighton and Sussex University Hospitals NHS Trust	Recruiting
Brighton, United Kingdom
Contact: Yvonne Gilleece
Principal Investigator: Yvonne Gilleece
C&W Hospital, London	Recruiting
London, United Kingdom
Principal Investigator: David Hawkins, MD, PhD
North Middlesex Hospital	Recruiting
London, United Kingdom
Contact: Chris Wood
Principal Investigator: Chris Wood
North Middlesex Hospital	Recruiting
London, United Kingdom
Contact: C Wood
Principal Investigator: C Wood, MD
St Mary's Hospital, London	Recruiting
London, United Kingdom
Principal Investigator: Graham Taylor, MD, PhD
St Thomas Hospital	Not yet recruiting
London, United Kingdom
Contact: J Fox
Principal Investigator: J Fox, MD
St. George's Hospital, London	Recruiting
London, United Kingdom
Principal Investigator: Tariq Sadiq, PhD

Sponsors and Collaborators

Radboud University

PENTA Foundation

Merck Sharp & Dohme Corp.

Bristol-Myers Squibb

Janssen Pharmaceutica

ViiV Healthcare

Investigators

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Principal Investigator:	David M Burger, PharmD PhD	Radboud University Medical Centre Nijmegen

More Information

Publications of Results:

Colbers AP, Hawkins DA, Gingelmaier A, Kabeya K, Rockstroh JK, Wyen C, Weizsäcker K, Sadiq ST, Ivanovic J, Giaquinto C, Taylor GP, Moltó J, Burger DM; PANNA network. The pharmacokinetics, safety and efficacy of tenofovir and emtricitabine in HIV-1-infected pregnant women. AIDS. 2013 Mar 13;27(5):739-48. doi: 10.1097/QAD.0b013e32835c208b.

Colbers A, Gingelmaier A, van der Ende M, Rijnders B, Burger D. Pharmacokinetics, safety and transplacental passage of rilpivirine in pregnancy: two cases. AIDS. 2014 Jan 14;28(2):288-90. doi: 10.1097/QAD.0000000000000100.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kreitchmann R, Schalkwijk S, Best B, Wang J, Colbers A, Stek A, Shapiro D, Cressey T, Mirochnick M, Burger D. Efavirenz pharmacokinetics during pregnancy and infant washout. Antivir Ther. 2019;24(2):95-103. doi: 10.3851/IMP3283.

Schalkwijk S, Colbers A, Konopnicki D, Gingelmaier A, Lambert J, van der Ende M, Moltó J, Burger D; Pharmacokinetics of newly developed antiretroviral agents in HIV-infected pregnant women (PANNA) Network. Lowered Rilpivirine Exposure During the Third Trimester of Pregnancy in Human Immunodeficiency Virus Type 1-Infected Women. Clin Infect Dis. 2017 Oct 15;65(8):1335-1341. doi: 10.1093/cid/cix534.

Mulligan N, Schalkwijk S, Best BM, Colbers A, Wang J, Capparelli EV, Moltó J, Stek AM, Taylor G, Smith E, Hidalgo Tenorio C, Chakhtoura N, van Kasteren M, Fletcher CV, Mirochnick M, Burger D. Etravirine Pharmacokinetics in HIV-Infected Pregnant Women. Front Pharmacol. 2016 Aug 4;7:239. doi: 10.3389/fphar.2016.00239. eCollection 2016.

Colbers A, Best B, Schalkwijk S, Wang J, Stek A, Hidalgo Tenorio C, Hawkins D, Taylor G, Kreitchmann R, Burchett S, Haberl A, Kabeya K, van Kasteren M, Smith E, Capparelli E, Burger D, Mirochnick M; PANNA Network and the IMPAACT 1026 Study Team. Maraviroc Pharmacokinetics in HIV-1-Infected Pregnant Women. Clin Infect Dis. 2015 Nov 15;61(10):1582-9. doi: 10.1093/cid/civ587. Epub 2015 Jul 22.

Blonk MI, Colbers AP, Hidalgo-Tenorio C, Kabeya K, Weizsäcker K, Haberl AE, Moltó J, Hawkins DA, van der Ende ME, Gingelmaier A, Taylor GP, Ivanovic J, Giaquinto C, Burger DM; Pharmacokinetics of Newly Developed Antiretroviral Agents in HIV-Infected Pregnant Women PANNA Network; PANNA Network. Raltegravir in HIV-1-Infected Pregnant Women: Pharmacokinetics, Safety, and Efficacy. Clin Infect Dis. 2015 Sep 1;61(5):809-16. doi: 10.1093/cid/civ366. Epub 2015 May 5.

Colbers A, Moltó J, Ivanovic J, Kabeya K, Hawkins D, Gingelmaier A, Taylor G, Weizsäcker K, Sadiq ST, Van der Ende M, Giaquinto C, Burger D; PANNA Network. Pharmacokinetics of total and unbound darunavir in HIV-1-infected pregnant women. J Antimicrob Chemother. 2015 Feb;70(2):534-42. doi: 10.1093/jac/dku400. Epub 2014 Oct 17.

Colbers A, Hawkins D, Hidalgo-Tenorio C, van der Ende M, Gingelmaier A, Weizsäcker K, Kabeya K, Taylor G, Rockstroh J, Lambert J, Moltó J, Wyen C, Sadiq ST, Ivanovic J, Giaquinto C, Burger D; PANNA network. Atazanavir exposure is effective during pregnancy regardless of tenofovir use. Antivir Ther. 2015;20(1):57-64. doi: 10.3851/IMP2820. Epub 2014 Jul 3.

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Responsible Party:	Radboud University
ClinicalTrials.gov Identifier:	NCT00825929 History of Changes
Other Study ID Numbers:	UMCN-AKF 08.02
First Posted:	January 21, 2009 Key Record Dates
Last Update Posted:	January 23, 2019
Last Verified:	January 2019

Keywords provided by Radboud University:


pharmacokinetics pregnancy antiretrovirals	neonates HIV treatment experienced

Additional relevant MeSH terms:

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HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral	Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents

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