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A Single-arm, Open-label, Study to Assess the Pharmacokinetics of Darunavir and Ritonavir, Darunavir and Cobicistat, Etravirine, and Rilpivirine in HIV-1 Infected Pregnant Women

6. juni 2018 opdateret af: Janssen Scientific Affairs, LLC

A Single Arm, Open Label Study to Assess the Pharmacokinetics of Darunavir and Ritonavir, Darunavir and Cobicistat, Etravirine, and Rilpivirine in HIV-1 Infected Pregnant Women

The purpose of this study is to study how changes in the body during pregnancy influence the blood levels of TMC114 (darunavir) and ritonavir taken together, darunavir and cobicistat taken as a fixed-dose combination, TMC125 (etravirine) taken alone or with darunavir and ritonavir or rilpivirine in patients with human immunodeficiency virus-1 (HIV-1). This study will examine how these drugs are absorbed in the body, how they are distributed within the body and how they are removed from the body over time. Any pregnant woman who is currently receiving darunavir with ritonavir, darunavir with cobicistat, etravirine or rilpivirine for HIV-1, and who meets the eligibility criteria for the study, will be allowed to enroll. Patients must be willing to remain on study medication during the course of their pregnancy, and 12 weeks postpartum. The information collected may help answer questions about how to best prescribe these three drugs for pregnant women.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

There are many biological changes that occur during pregnancy, some of which may affect the way HIV medications are absorbed, distributed and removed within the body. Some medications have been used for HIV treatment during pregnancy, but little is known about how pregnancy affects the class of drugs being used in this study. To participate in this study, patients must be receiving 600mg of TMC114 (darunavir) taken with 100mg ritonavir twice daily or 800mg of TMC114 (darunavir) with 100mg of ritonavir once daily or 800 mg of darunavir taken with 150mg of cobicistat taken once daily or 200mg of TMC125 (etravirine) (with or without darunavir/ ritonavir) taken twice daily or 25mg of TMC278 (rilpivirine) taken once daily plus additional antiretroviral drugs needed to construct an active antiretroviral regimen. Darunavir and ritonavir, darunavir and cobicistat, etravirine, or rilpivirine will be supplied to study participants. Darunavir and ritonavir are human immunodeficiency virus (HIV) protease inhibitors (PIs); cobicistat is a pharmacoenhancer which boosts the levels of darunavir but has no anti-HIV activity; etravirine and rilpivirine are non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV. Twelve-hour or twenty four-hour blood sampling will be done for each patient at each of three study visits: Visit 4 (2nd trimester), Visit 5 (3rd trimester), and Visit 8 (6-12 weeks postpartum). Eight blood draws will be taken during each visit: One prior to intake of study medication, and one for each of seven post-dose sampling time-points (hours 1, 2, 3, 4, 6, 9 and 12). The study is designed primarily to examine the pharmacokinetics of darunavir/ritonavir (darunavir/r), darunavir/ cobicistat, etravirine or rilpivirine during the second and third trimesters of gestation, as well as postpartum. Pharmacokinetics measures how the body absorbs, distributes and excretes medication. The study will also examine any changes in anti-viral activity during pregnancy, and the postpartum period. It will note any safety and tolerability of the medications used by the mother, and will measure the level of darunavir/ritonavir, darunavir/ cobicistat, etravirine or rilpivirine in the newborn's cord blood at the time of delivery; outcomes for both mother and child will be assessed as well. During the treatment period, patients will be seen at regular visits in the clinic, where the investigator will assess the patient's medical condition, any Adverse Events and study drug compliance. Laboratory evaluations for efficacy and safety will be done at regular visits as well as blood pressure monitoring. Up to forty-eight (48) HIV positive pregnant women will participate in this study. Study enrollment will be closed once 12 evaluable patients taking darunavir/ritonavir once daily, 12 evaluable patients taking darunavir/cobicistat once daily, 12 evaluable patients taking darunavir/ritonavir twice daily, 12 evaluable patients taking etravirine taking twice daily and 12 evaluable patients taking rilpivirine once daily have been enrolled. The study will be conducted at approximately 14 research centers in the United States and 1 in Puerto Rico. In order to participate, patients must be pregnant for 13-24 weeks. The primary purpose (or outcome) of the study is to assess the influence of pregnancy on the pharmacokinetics of darunavir/ritonavir, darunavir/ cobicistat, etravirine or rilpivirine during the second and third trimesters of gestation, as well as postpartum. Darunavir: One 600 mg or two 300 mg tablets taken twice daily by mouth (two or four tablets a day total). Ritonavir: 100mg tablet taken twice daily by mouth (two tablets a day total), together with darunavir. Darunavir: Two 400 mg tablets taken once daily by mouth (two tablets a day total). Ritonavir: 100mg tablet taken once daily by mouth (one tablet a day total), together with darunavir. Darunavir/ cobicistat: a fixed dose combination containing 800mg of darunavir and 150mg of cobicistat. Etravirine: Two 100 mg tablets taken twice daily by mouth (four tablets a day total). Rilpivirine: One 25mg tablet taken once daily by mouth (one tablet a day total). Study medication will be given from the baseline visit (second pregnancy trimester) until Visit 8 (up to 12 weeks after delivery).

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

77

Fase

  • Fase 3

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Forenede Stater
    • Florida
      • Daytona Beach, Florida, Forenede Stater
      • Jacksonville, Florida, Forenede Stater
      • Miami, Florida, Forenede Stater
      • Pensacola, Florida, Forenede Stater
      • Port Saint Lucie, Florida, Forenede Stater
      • West Palm Beach, Florida, Forenede Stater
    • Georgia
      • Savannah, Georgia, Forenede Stater
    • Illinois
      • Chicago, Illinois, Forenede Stater
    • Massachusetts
      • Springfield, Massachusetts, Forenede Stater
    • Michigan
      • Dearborn, Michigan, Forenede Stater
    • New York
      • Bronx, New York, Forenede Stater
      • Syracuse, New York, Forenede Stater
    • North Carolina
      • Chapel Hill, North Carolina, Forenede Stater
      • Greensboro, North Carolina, Forenede Stater
    • Pennsylvania
      • Philadelphia, Pennsylvania, Forenede Stater
    • Texas
      • Bellaire, Texas, Forenede Stater
  • Puerto Rico
      • San Juan Pr, Puerto Rico

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Kvinde

Beskrivelse

Inclusion Criteria:

  • Pregnant females (18-26 weeks of gestation)
  • documented HIV-1 infection
  • Receiving darunavir/ritonavir, darunavir/cobicistat, etravirine, or rilpivirine at the time of study entry
  • Willing to remain on darunavir/ritonavir, darunavir/cobicistat, etravirine, or rilpivirine as well as a background regimen, for the duration of the study, including 12 weeks postpartum
  • Able to comply with the protocol requirements and to provide written informed consent.

Exclusion Criteria:

  • Patients with any currently active acquired immune deficiency syndrome (AIDS) defining illness and AIDS-related opportunistic infection
  • Patients using cytokine inhibitors (e.g., thalidomide), anabolic hormones, cytokines (e.g., IL-2, INF), efavirenz, hydroxyurea, oral hypoglycemics, systemic chemotherapy or known teratogenic agent
  • Use of an investigational agent within 90 days
  • Any known fetal anomaly
  • Any current obstetric complication, including multiple gestations and pre-term labor
  • Hepatitis B and/or C virus infection
  • Grade 2 or higher anemia
  • Thyroid disease
  • Uncontrolled Diabetes Mellitus Types I and II, or gestational diabetes, as determined by the investigator

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Group 1: Darunavir 600 /Ritonavir 100
TMC114 (darunavir) Two 300 milligram (mg) or one 600 mg tablet twice daily up to 12 weeks postpartum / ritonavir one 100 mg tablet twice daily with darunavir up to 12 weeks postpartum.
Medicin: Darunavir
TMC114 (darunavir) two 300 mg or one 600 mg tablet twice daily up to 12 weeks postpartum in Group 1. TMC114 (darunavir) 800mg tablet once daily up to 12 weeks postpartum in Group 2.
Medicin: Ritonavir
100 mg tablet twice daily up to 12 weeks postpartum.
Eksperimentel: Group 2: Darunavir 800/Ritonavir 100
TMC114 (darunavir) 800mg tablet once daily up to 12 weeks postpartum/ ritonavir one 100 mg tablet once daily with darunavir up to 12 weeks postpartum.
Medicin: Darunavir
TMC114 (darunavir) two 300 mg or one 600 mg tablet twice daily up to 12 weeks postpartum in Group 1. TMC114 (darunavir) 800mg tablet once daily up to 12 weeks postpartum in Group 2.
Medicin: Ritonavir
100 mg tablet twice daily up to 12 weeks postpartum.
Eksperimentel: Group 3: Etravirine
TMC125 (etravirine) 200 mg (1*200 mg/2*100 mg) tablets twice daily up to 12 weeks postpartum.
Medicin: Etravirine
200 mg (1*200 mg/2*100 mg) tablets twice daily up to 12 weeks postpartum.
Eksperimentel: Group 4: Rilpivirine
TMC278 (rilpivirine) One 25 mg tablet once daily up to 12 weeks postpartum.
Medicin: Rilpivirine
One 25 mg tablet once daily up to 12 weeks postpartum.
Eksperimentel: Group 5: Darunavir 800/Cobicistat 150
Fixed dose combination (FDC) tablet of TMC114 (darunavir) 800 mg and cobicistat 150 mg once daily up to 12 weeks postpartum.
Medicin: Darunavir/Cobicistat (FDC)
Fixed dose combination (FDC) tablet of TMC114 (darunavir) 800 mg and cobicistat 150 mg once daily up to 12 weeks postpartum.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Predose (Trough) Plasma Concentration (C0h)
Tidsramme: Predose on Weeks 24-28 (Visit 4, 2nd trimester), 34-38 (visit 5, 3rd trimester) and 6-12 weeks postpartum (visit 8)
C0h is defined as the predose (trough) plasma concentration or concentration just prior to study drug administration.
Predose on Weeks 24-28 (Visit 4, 2nd trimester), 34-38 (visit 5, 3rd trimester) and 6-12 weeks postpartum (visit 8)
Minimum Plasma Concentration (Cmin)
Tidsramme: Between Predose and 24 hours postdose at Weeks 24-28 (Visit 4, 2nd trimester), 34-38 (visit 5, 3rd trimester) and 6-12 weeks postpartum (visit 8)
The Cmin is the minimum observed plasma concentration.
Between Predose and 24 hours postdose at Weeks 24-28 (Visit 4, 2nd trimester), 34-38 (visit 5, 3rd trimester) and 6-12 weeks postpartum (visit 8)
Maximum Plasma Concentration (Cmax)
Tidsramme: Between Predose and 24 hours postdose at Weeks 24-28 (Visit 4, 2nd trimester), 34-38 (visit 5, 3rd trimester) and 6-12 weeks postpartum (visit 8)
The Cmax is the maximum observed plasma concentration.
Between Predose and 24 hours postdose at Weeks 24-28 (Visit 4, 2nd trimester), 34-38 (visit 5, 3rd trimester) and 6-12 weeks postpartum (visit 8)
Time to Reach the Maximum Plasma Concentration (Tmax)
Tidsramme: Between Predose and 24 hours postdose at Weeks 24-28 (Visit 4, 2nd trimester), 34-38 (visit 5, 3rd trimester) and 6-12 weeks postpartum (visit 8)
The Tmax is defined as actual sampling time to reach maximum observed plasma concentration.
Between Predose and 24 hours postdose at Weeks 24-28 (Visit 4, 2nd trimester), 34-38 (visit 5, 3rd trimester) and 6-12 weeks postpartum (visit 8)
Area Under the Plasma Concentration-Time Curve From Time of Administration to 12 Hours Post-dose (AUC0-12h)
Tidsramme: Between Predose and 24 hours postdose at Weeks 24-28 (Visit 4, 2nd trimester), 34-38 (visit 5, 3rd trimester) and 6-12 weeks postpartum (visit 8)
The AUC (0-12) is the area under the plasma concentration-time curve from time zero to 12 hours post dose. The selected arms were based on the dosing frequency (twice daily).
Between Predose and 24 hours postdose at Weeks 24-28 (Visit 4, 2nd trimester), 34-38 (visit 5, 3rd trimester) and 6-12 weeks postpartum (visit 8)
Area Under the Plasma Concentration-Time Curve From Time of Administration to 24 Hours Post-dose (AUC0-24h)
Tidsramme: Between Predose and 24 hours postdose at Weeks 24-28 (Visit 4, 2nd trimester), 34-38 (visit 5, 3rd trimester) and 6-12 weeks postpartum (visit 8)
The AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours post dose. The selected arms were based on the dosing frequency (once daily).
Between Predose and 24 hours postdose at Weeks 24-28 (Visit 4, 2nd trimester), 34-38 (visit 5, 3rd trimester) and 6-12 weeks postpartum (visit 8)

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Number of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) Plasma Viral Load (<) 50 Copies/Milliliter (mL)
Tidsramme: Up to postpartum (6-12 weeks)
Number of participants were assessed with a viral load (VL) lesser than (<) 50 HIV-1 RNA copies/ mL over time.
Up to postpartum (6-12 weeks)
Mean Change From Baseline in Log10 Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) Viral Load Value
Tidsramme: Baseline, 4 weeks after baseline, 2nd and 3rd trimesters of pregnancy and postpartum (2-5 weeks and 6-12 weeks)
Mean change from baseline in log 10 HIV-1 RNA VL was assessed up to postpartum (6-12 weeks).
Baseline, 4 weeks after baseline, 2nd and 3rd trimesters of pregnancy and postpartum (2-5 weeks and 6-12 weeks)
Mean Change From Baseline in CD4+ Cell Count
Tidsramme: Baseline, 4 weeks after baseline, 2nd and 3rd trimesters of pregnancy and postpartum (2-5 weeks and 6-12 weeks)
Mean Change From Baseline in CD4+ Cell Count were assessed for immunology testing.
Baseline, 4 weeks after baseline, 2nd and 3rd trimesters of pregnancy and postpartum (2-5 weeks and 6-12 weeks)
Number of Participants With Resistance at Virological Failure
Tidsramme: Up to follow-up phase (16 weeks after postpartum)
Resistance analysis was determined using genotypic and phenotypic analysis at the time of virological failure. For participants with a baseline viral load greater than (>) 200 copies/mL, virologic failure was defined as follows: HIV ribonucleic acid (RNA) levels that did not fall by at least 0.5 log 4 weeks after Baseline; viral load >1000 copies/mL (at 2 successive visits) by gestational weeks 34-38; or viral load >200 copies/mL (at 2 successive visits) after reaching a viral load less than or equal to (<=) 200 copies/mL. For participants with a baseline viral load <=200 copies/mL, virologic failure was defined as viral load of >200 copies/mL (at 2 successive visits) at any point during the study.
Up to follow-up phase (16 weeks after postpartum)
Plasma Concentration of Drug in the Cord Plasma and Maternal Plasma Samples Collected at the Time of Delivery
Tidsramme: On day of delivery - Intrapartum (Visit 6)
The drug concentrations were evaluated in the cord plasma and maternal plasma samples collected at the time of delivery.
On day of delivery - Intrapartum (Visit 6)
Number of Infants With Human Immunodeficiency Virus (HIV) Positive Test Result
Tidsramme: Birth to age 16 weeks
The infants were evaluated for HIV positive tests using HIV polymerase chain reaction test (PCR).
Birth to age 16 weeks
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Tidsramme: Up to follow up period (16 weeks after postpartum)
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Up to follow up period (16 weeks after postpartum)

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Janssen Scientific Affairs, LLC

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

9. april 2009

Primær færdiggørelse (Faktiske)

11. august 2016

Studieafslutning (Faktiske)

11. august 2016

Datoer for studieregistrering

Først indsendt

2. marts 2009

Først indsendt, der opfyldte QC-kriterier

2. marts 2009

Først opslået (Skøn)

4. marts 2009

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

6. juli 2018

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

6. juni 2018

Sidst verificeret

1. maj 2018

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • CR015442
  • TMC114HIV3015 (Anden identifikator: Janssen Scientific Affairs, LLC)

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

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Ingen

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