- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT00076791
Safety of Tenofovir Disoproxil Fumarate (TDF) and Emtricitabine/TDF in HIV Infected Pregnant Women and Their Infants
A Phase I Study of the Safety, Tolerance, and Pharmacokinetics of Tenofovir Disoproxil Fumarate (TDF) and the Combination of TDF Plus Emtricitabine in HIV-1 Infected Pregnant Women and Their Infants
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
The majority of perinatally infected infants are infected during the labor and delivery process, but recent studies suggest that additional factors, such as postexposure prophylaxis, are likely to be involved in the prevention of MTCT of HIV. It is possible that antiretroviral dosing only during labor and short-term dosing to newly born infants would be sufficiently effective to prevent MTCT of HIV. TDF is a nucleoside reverse transcriptase inhibitor that has demonstrated significant effectiveness in preventing MTCT of simian immunodeficiency virus (SIV) in a primate model of HIV. FTC/TDF is a combination of two NRTIs being studied because this combination has the potential to prevent MTCT, while protecting the mother from developing resistance that may develop with single drug therapy. This study will evaluate the safety, tolerance, and pharmacokinetics (PK) of single doses of TDF and FTC/TDF in both HIV infected pregnant women and their newborn infants.
Cohort 1 is now closed. Each participant in Cohort 1 received a single 600 mg oral dose of TDF at the start of active labor or 4 hours prior to C-section, with concurrent administration of standard intravenous zidovudine (ZDV) prophylaxis and/or other antiretrovirals prescribed by her physician. The infants from Cohort 1 received only the standard 6 weeks of oral ZDV prophylaxis postpartum. PK blood samples were taken from mothers at predose and 1, 2, 4, 8, 12, and 24 hours postdose and at the time of delivery; PK blood samples were taken from infants at 12, 24, and 36 hours after birth.
Pregnant women with HIV infection entering this study will be assigned to Cohort 2, as all infants in Cohort 1 have completed the 6 to 8 week study visit and all Cohort 1 data have been reviewed. Mothers in Cohort 2 will receive a single dose of 900 mg of TDF combined with 600 mg emtricitabine, along with standard ZDV prophylaxis and/or other antiretrovirals prescribed by her physician. Infants will receive a single dose of TDF at 4 mg/kg combined with 3 mg/kg emtricitabine as soon as possible after delivery and within 6 hours of age as well as the standard 6 weeks of oral ZDV prophylaxis after birth. Blood samples from mothers and infants will be taken as for Cohort 1.
Mothers will be followed for 12 weeks postpartum or for 2 years after giving birth if viral resistance to TDF or FTC/TDF is demonstrated at Weeks 1, 6, or 12. In addition to the PK studies, blood collection will occur around the time of delivery, at screening, study entry, at delivery, and after delivery at various times up to Week 12. Physical exams will be done at screening, study entry, at delivery, and after delivery at various times up to Week 8. Infants will be followed until age 2. Blood will be collected and physical exams will be done at birth and at various times up to Week 96. Mothers are encouraged to coenroll in PACTG P1025, Pharmacokinetic Study of Anti-HIV Drugs During Pregnancy.
Studietype
Registrering (Faktiske)
Fase
- Fase 1
Kontakter og plasseringer
Studiesteder
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District of Columbia
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Washington, District of Columbia, Forente stater, 20010
- Children's National Med. Ctr. Washington DC NICHD CRS
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Washington, District of Columbia, Forente stater, 20010
- Washington Hosp. Ctr. NICHD CRS
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Florida
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Miami, Florida, Forente stater, 33136
- Univ. of Miami Ped. Perinatal HIV/AIDS CRS
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Illinois
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Chicago, Illinois, Forente stater, 60608
- Mt. Sinai Hosp. Med. Ctr. - Chicago, Womens & Childrens HIV Program
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Michigan
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Detroit, Michigan, Forente stater, 48201
- Children's Hospital of Michigan NICHD CRS
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New Jersey
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Newark, New Jersey, Forente stater, 07101-1709
- NJ Med. School CRS
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New York
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Bronx, New York, Forente stater, 10457
- Bronx-Lebanon Hosp. IMPAACT CRS
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New York, New York, Forente stater, 10016
- Nyu Ny Nichd Crs
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Pennsylvania
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Philadelphia, Pennsylvania, Forente stater, 19102-1192
- Hahnemann Univ. Hosp.
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Tennessee
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Memphis, Tennessee, Forente stater
- Regional Med. Ctr. at Memphis
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Memphis, Tennessee, Forente stater
- St. Jude/UTHSC CRS
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San Juan, Puerto Rico
- San Juan City Hosp. PR NICHD CRS
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
Inclusion Criteria for Mothers:
- HIV infected
- 34 weeks or more (third trimester) into pregnancy at study screening
- Have access to a participating AIDS clinical trial unit (ACTU) and are willing to be followed at location for the duration of the study
Exclusion Criteria for Mothers:
- Prior treatment with TDF, including coformulated drugs that contain TDF, during current pregnancy
- Active opportunistic infection and/or serious bacterial infection at time of study entry
- Certain abnormal laboratory values at study screening
- Chronic malabsorption or chronic diarrhea
- Certain medical or obstetrical complications during the current pregnancy
- Fetal abnormalities as measured by ultrasound screening performed at 18 weeks into pregnancy or later
- Intend to breastfeed
- Current alcohol abuse or use of illicit substances
- Participation in any other therapeutic or vaccine perinatal treatment trial during the current pregnancy, unless given permission by the protocol chairs
- Require certain medications
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Forebygging
- Tildeling: Ikke-randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
---|---|
Aktiv komparator: 1
Each participant in Cohort 1 received a single 600 mg oral dose of TDF at the start of active labor or 4 hours prior to C-section, with concurrent administration of standard intravenous zidovudine (ZDV) prophylaxis and/or other antiretrovirals prescribed by her physician.
The infants from Cohort 1 received only the standard 6 weeks of oral ZDV prophylaxis postpartum.
|
900 mg of TDF combined with 600 mg emtricitabine
600 mg oral dose of TDF
|
Aktiv komparator: 2
Mothers in Cohort 2 will receive a single dose of 900 mg of TDF combined with 600 mg emtricitabine, along with standard ZDV prophylaxis and/or other antiretrovirals prescribed by her physician.
Infants will receive a single dose of TDF at 4 mg/kg combined with 3 mg/kg emtricitabine as soon as possible after delivery and within 6 hours of age as well as the standard 6 weeks of oral ZDV prophylaxis after birth.
|
900 mg of TDF combined with 600 mg emtricitabine
600 mg oral dose of TDF
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tidsramme |
---|---|
Adverse experiences with a severity of Grade 3 or 4 and adverse pregnancy outcomes that cannot be directly attributed to a cause besides study treatment
Tidsramme: Throughout study
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Throughout study
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Sekundære resultatmål
Resultatmål |
Tidsramme |
---|---|
Maternal viral load
Tidsramme: during active labor and 24 to 48 hours, 7 days, 6 to 8 weeks, and 12 weeks postpartum
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during active labor and 24 to 48 hours, 7 days, 6 to 8 weeks, and 12 weeks postpartum
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viral resistance to emtricitabine/tenofovir disoproxil fumarate using bulk sequencing
Tidsramme: at Weeks 1, 6, and 12 postpartum
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at Weeks 1, 6, and 12 postpartum
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infant HIV DNA PCR
Tidsramme: at 24 to 48 hours, 6 to 8 weeks, 4 months, and 6 months of life
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at 24 to 48 hours, 6 to 8 weeks, 4 months, and 6 months of life
|
Samarbeidspartnere og etterforskere
Samarbeidspartnere
Etterforskere
- Studiestol: Patricia M. Flynn, MD, Department of Infectious Disease, St. Jude's Children's Research Hospital
- Studiestol: Arlene D. Bardeguez, MD, MPH, FACOG, Obstetrics, Gynecology, and Women's Health, University of Medicine and Dentistry of New Jersey
Publikasjoner og nyttige lenker
Generelle publikasjoner
- Abrams EJ. Prevention of mother-to-child transmission of HIV--successes, controversies and critical questions. AIDS Rev. 2004 Jul-Sep;6(3):131-43.
- Antoniou T, Park-Wyllie LY, Tseng AL. Tenofovir: a nucleotide analog for the management of human immunodeficiency virus infection. Pharmacotherapy. 2003 Jan;23(1):29-43. doi: 10.1592/phco.23.1.29.31915.
- Kourtis AP, Duerr A. Prevention of perinatal HIV transmission: a review of novel strategies. Expert Opin Investig Drugs. 2003 Sep;12(9):1535-44. doi: 10.1517/13543784.12.9.1535.
- Moodley J, Moodley D. Management of human immunodeficiency virus infection in pregnancy. Best Pract Res Clin Obstet Gynaecol. 2005 Apr;19(2):169-83. doi: 10.1016/j.bpobgyn.2004.10.007. Epub 2004 Dec 15.
- Thorne C, Newell ML. The safety of antiretroviral drugs in pregnancy. Expert Opin Drug Saf. 2005 Mar;4(2):323-35. doi: 10.1517/14740338.4.2.323.
Studierekorddatoer
Studer hoveddatoer
Studiestart
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
- RNA-virusinfeksjoner
- Virussykdommer
- Infeksjoner
- Blodbårne infeksjoner
- Smittsomme sykdommer
- Seksuelt overførbare sykdommer, virale
- Seksuelt overførbare sykdommer
- Lentivirus infeksjoner
- Retroviridae-infeksjoner
- Immunologiske mangelsyndromer
- Sykdommer i immunsystemet
- HIV-infeksjoner
- Molekylære mekanismer for farmakologisk virkning
- Anti-infeksjonsmidler
- Antivirale midler
- Revers transkriptasehemmere
- Nukleinsyresyntesehemmere
- Enzymhemmere
- Anti-HIV-midler
- Antiretrovirale midler
- Tenofovir
- Emtricitabin
- Emtricitabin, Tenofovir Disoproxil Fumarate Legemiddelkombinasjon
Andre studie-ID-numre
- P394
- 10034 (Registeridentifikator: DAIDS ES)
- PACTG 394
- IMPAACT 394
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .
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