Clinical trial NCT00825929: Pharmacokinetics of Antiretroviral Agents in HIV-infected Pregnant Women.
Official title: Study on Pharmacokinetics of Newly Developed ANtiretroviral Agents in HIV-infected pregNAnt Women (PANNA)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: HIV Infections
Keywords: pharmacokinetics
pregnancy
antiretrovirals
neonates
HIV
treatment experienced
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: PENTA Foundation
name: Merck Sharp & Dohme LLC
name: Bristol-Myers Squibb
name: Janssen Pharmaceutica
name: ViiV Healthcare
name: Gilead Sciences
First posted: 2009-01-21
Enrollment: 176
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CROSSOVER
Time perspective: PROSPECTIVE
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; abacavir; raltegravir, Isentress; Enfuvirtide, Fuzeon; Maraviroc, Celsentri; dolutegravir; elvitegravir/cobicistat; rilpivirine, TAF, darunavir/cobicistat; doravirine; bictegravir; cabotegravir/rilpivirine LA

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.

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; doravirine; bictegravir; cabotegravir/rilpivirine long acting injectables

Eligibility criteria: Inclusion Criteria:

1. HIV-infected as documented by positive HIV antibody test and confirmed by an antigen test.
2. Subject is at least 18 years of age at screening.
3. Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
4. 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.
5. Subject is pregnant
6. Subject is able to adhere to food intake recommendations, if applicable.

Exclusion Criteria:

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

Primary outcomes:
measure: Plasma concentrations of the compounds during pregnancy compared to the concentrations after delivery
timeFrame: PK curve in Week 33 of pregnancy and 4-6 weeks after delivery
Secondary outcomes:
measure: Pharmacokinetics in the neonate, in case of post-exposure prophylaxis with one of the agents under study.
timeFrame: Week 1, 3 and between 4 and 6
measure: Safety of antiretrovirals during pregnancy
timeFrame: GA Week 33 until end of trial
measure: viral load response and prevention of mother to child transmission of the virus
timeFrame: GA Week 3 and at delivery
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Saint-Pierre University Hospital; Department of Infectious Diseases
city: Berlin
country: Germany
facility: CHARITÉ Berlin
city: Bonn
country: Germany
facility: University of Bonn
city: Cologne
country: Germany
facility: University of Cologne
city: Frankfurt am Main
country: Germany
facility: Johann Wolfgang Goethe-Universität
city: München
country: Germany
facility: University München
city: Dublin
country: Ireland
facility: Mater Hospital and UCD
city: Dublin
country: Ireland
facility: St James's Hospital Dublin
city: Rome
country: Italy
facility: IRCSS
city: Amsterdam
country: Netherlands
facility: AMC
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Centre
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center Rotterdam
city: Tilburg
country: Netherlands
facility: St Elisabeth hospital
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol, Badalona
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves Granada; Médico Adjunto del Servicio de Medicina Interna
city: Brighton
country: United Kingdom
facility: Brighton and Sussex University Hospitals NHS Trust
city: London
country: United Kingdom
facility: C&W Hospital, London
city: London
country: United Kingdom
facility: North Middlesex Hospital
city: London
country: United Kingdom
facility: St Mary's Hospital, London
city: London
country: United Kingdom
facility: St Thomas Hospital
city: London
country: United Kingdom
facility: St. George's Hospital, London
Study officials:
affiliation: Radboud University Medical Centre Nijmegen
name: David M Burger, PharmD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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. 2021 Jan 23;72(1):121-127. doi: 10.1093/cid/ciaa006.
citation: 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(10):e714-e717. doi: 10.1093/cid/ciaa488.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Blonk MI, Colbers AP, Hidalgo-Tenorio C, Kabeya K, Weizsacker K, Haberl AE, Molto 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.
citation: Colbers A, Molto J, Ivanovic J, Kabeya K, Hawkins D, Gingelmaier A, Taylor G, Weizsacker 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.
citation: Colbers A, Hawkins D, Hidalgo-Tenorio C, van der Ende M, Gingelmaier A, Weizsacker K, Kabeya K, Taylor G, Rockstroh J, Lambert J, Molto 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.