Pharmacokinetics of Antiretroviral Agents in HIV-infected Pregnant Women.

Официальное название

Study on Pharmacokinetics of Newly Developed ANtiretroviral Agents in HIV-infected pregNAnt Women (PANNA)

Обзор

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.

Подробное описание

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; doravirine; bictegravir; cabotegravir/rilpivirine long acting injectables

Первичные конечные точки

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

Вторичные конечные точки (3)

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

Критерии участия

Критерии включения

• HIV-infected as documented by positive HIV antibody test and confirmed by an antigen test.
• 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 a cART regimen containing at least one agent which is mentioned in Appendix 1; this agent has been taken for at least 2 weeks before the day of first PK curve evaluation.
• Subject is pregnant
• Subject is able to adhere to food intake recommendations, if applicable.

Критерии исключения

• 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).
• Using oral cabotegravir/rilpivirine.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Случай-кроссовер

Центры проведения

Великобритания · 6 центров

• Brighton and Sussex University Hospitals NHS Trust — Brighton
• C&W Hospital, London — London
• North Middlesex Hospital — London
• St Mary's Hospital, London — London
• St Thomas Hospital — London
• St. George's Hospital, London — London

Германия · 5 центров

• CHARITÉ Berlin — Berlin
• University of Bonn — Bonn
• University of Cologne — Cologne
• Johann Wolfgang Goethe-Universität — Frankfurt am Main
• University München — München

Нидерланды · 4 центра

• AMC — Amsterdam
• Radboud University Nijmegen Medical Centre — Nijmegen
• Erasmus Medical Center Rotterdam — Rotterdam
• St Elisabeth hospital — Tilburg

Ирландия · 2 центра

• Mater Hospital and UCD — Dublin
• St James's Hospital Dublin — Dublin

Испания · 2 центра

• Hospital Universitari Germans Trias i Pujol, Badalona — Badalona
• Hospital Universitario Virgen de las Nieves Granada; Médico Adjunto del Servicio de Medici — Granada

Бельгия · 1 центр

• Saint-Pierre University Hospital; Department of Infectious Diseases — Brussels

Италия · 1 центр

• IRCSS — Rome

Публикации

• Colbers AP, Hawkins DA, Gingelmaier A, Kabeya K, Rockstroh JK, Wyen C, Weizsacker K, Sadiq ST, Ivanovic J, Giaquinto C, Taylor GP, Molto 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. PMID 23169329
• 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. No abstract available. PMID 24413315
• Bollen P, Freriksen J, Konopnicki D, Weizsacker K, Hidalgo Tenorio C, Molto J, Taylor G, Alba-Alejandre I, van Crevel R, Colbers A, Burger D; Pharmacokinetics of ANtiretroviral agents in HIV-infected pregNAnt women Network. The Effect of Pregnancy on the Pharmacokinetics of Total and Unbound Dolutegravir and Its Main Metabolite in Women Living With Human Immunodeficiency Virus. Clin Infect Dis. 20 PMID 32103260
• Overbeek JK, van Erp NP, Burger DM, den Broeder AA, Koolen SLW, Huitema ADR, Ter Heine R. Population Pharmacokinetics of Cobicistat and its Effect on the Pharmacokinetics of the Anticancer Drug Olaparib. Clin Pharmacokinet. 2025 Mar;64(3):425-435. doi: 10.1007/s40262-025-01480-w. Epub 2025 Feb 5. PMID 39909979
• Bukkems V, Necsoi C, Tenorio CH, Garcia C, Rockstroh J, Schwarze-Zander C, Lambert JS, Burger D, Konopnicki D, Colbers A. Clinically Significant Lower Elvitegravir Exposure During the Third Trimester of Pregnant Patients Living With Human Immunodeficiency Virus: Data From the Pharmacokinetics of ANtiretroviral agents in HIV-infected pregNAnt women (PANNA) Network. Clin Infect Dis. 2020 Dec 17;71(1 PMID 32330231
• 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. PMID 30530925
• Schalkwijk S, Colbers A, Konopnicki D, Gingelmaier A, Lambert J, van der Ende M, Molto 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. PMID 28595298
• Mulligan N, Schalkwijk S, Best BM, Colbers A, Wang J, Capparelli EV, Molto 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. PMID 27540363

Идентификаторы

NCT: NCT00825929 · UMCN-AKF 08.02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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