A Study to Evaluate the Safety and Tolerance of Nelfinavir (NFV) Given With Zidovudine (ZDV) and Lamivudine (3TC) in HIV-Positive Pregnant Women and Their Infants
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections; Pregnancy
Intervention: Nelfinavir mesylate (Drug); Lamivudine (Drug); Zidovudine (Drug)
Phase: Phase 1
Status: Active, not recruiting
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s):
Yvonne Bryson, Study Chair
Mark Mirochnick, Study Chair
Alice Stek, Study Chair
Summary
The purpose of this study is to see if giving nelfinavir (NFV) plus zidovudine (ZDV) plus
lamivudine (3TC) to HIV-positive pregnant women and their babies is safe. This study will
also look at how long these drugs stay in the blood.
ZDV has been given to mothers in the past to reduce the chances of passing HIV on to their
babies. However, better treatments are needed to further reduce these chances and to better
suit the treatment needs of mothers and their children. Taking a combination of anti-HIV
drugs during pregnancy may be an answer.
Clinical Details
Official title: A Phase I Trial of the Safety, Tolerance, and Pharmacokinetics of Oral Nelfinavir (Viracept) Co-Administered With Zidovudine (ZDV) and Lamivudine (3TC) in HIV Infected Pregnant Women and Their Infants
Study design: Treatment, Safety Study
Detailed description:
Despite the dramatic reduction of perinatal HIV transmission by the administration of ZDV to
mother and infant, new and more potent strategies are needed to further reduce perinatal
transmission and better suit the diverse treatment needs of these patients. Initiation of
triple antiretroviral combinations during gestation, particularly combinations that include
drugs that cross the placenta such as 3TC, may be the most effective in reducing maternal
virus load to its lowest levels prior to delivery.
Women receive nelfinavir plus 3TC plus ZDV antepartum (Study Day 0 until onset of active
labor) through postpartum (after cord clamped to 12 weeks). [AS PER AMENDMENT 10/28/97: If
patient presents in active labor with less than 1 hour to delivery time, the institutional
protocol for ZDV infusion during labor should be followed.] [AS PER AMENDMENT 1/26/99: For
maternal dosing, one Combivir tablet bid can be substituted for the individual formulation of
3TC and ZDV. For mothers who receive Combivir during the antepartum period, Combivir is held
during labor and delivery, and the separate formulations of ZDV and 3TC are used. Patients
who prematurely discontinue study treatment should continue to be followed on study for the
duration of the study.] Full pharmacokinetic sampling is performed 10 to 15 days after start
of therapy [AS PER AMENDMENT 2/7/00: 10 to 15 days after study entry for women currently
taking nelfinavir] and again 5 to 6 weeks after delivery. A maternal blood sample and cord
blood sample is collected at birth for analysis of nelfinavir concentrations. Maternal HIV
RNA in plasma is monitored throughout the study. Cervicovaginal secretions are collected at
entry, late gestation, and postpartum to assess the presence of HIV. A single
pharmacokinetics sample is collected with each cervicovaginal secretion. Serial CD4/CD8
activation markers are measured in women during gestation and postpartum. Infants receive
nelfinavir plus 3TC plus ZDV beginning approximately 12 hours following birth and continuing
for 6 weeks. After birth, several blood samples are collected from the infant for
determination of washout kinetics of nelfinavir. Full pharmacokinetics sampling is performed
5 to 8 days post birth and 5 to 6 weeks following multiple doses. Pharmacokinetic samples are
analyzed on the first six mother-infant pairs and dosing may be adjusted accordingly for the
next cohort. Agouron has agreed to make nelfinavir available to all interested study
participants for a period of 6 months after the study via the patient assistance program.
Eligibility
Minimum age: 13 Years.
Maximum age: N/A.
Gender(s): Female.
Criteria:
Inclusion Criteria
Patients may be eligible for this study if they:
- Are at least 13 years old (need consent of parent or guardian if under 18).
- Are HIV-positive.
- Are in the 2nd or 3rd trimester (14 to 34 weeks pregnant) and are pregnant with one or
two children.
- Have a normal ultrasound exam.
Exclusion Criteria
Patients will not be eligible for this study if they:
- Cannot take ZDV or 3TC.
- Have an active opportunistic (HIV-associated) or bacterial infection, or a severe
medical condition.
- Have severe diarrhea.
- Are at risk for premature birth or pregnancy complications.
- Have a family history of phenylketonuria (PKU).
- Plan to breast-feed.
- Abuse alcohol or drugs.
- Cannot visit the same clinic for the duration of the study.
- Have taken certain anti-HIV drugs.
Locations and Contacts
San Juan City Hosp, San Juan 009367344, Puerto Rico
UCSD Med Ctr / Pediatrics / Clinical Sciences, La Jolla, California 920930672, United States
Harbor - UCLA Med Ctr / UCLA School of Medicine, Los Angeles, California 905022004, United States
UCLA Med Ctr / Pediatric, Los Angeles, California 900951752, United States
Los Angeles County - USC Med Ctr, Los Angeles, California 90033, United States
Howard Univ Hosp, Washington, District of Columbia 20060, United States
Univ of Florida Health Science Ctr / Pediatrics, Jacksonville, Florida 32209, United States
Cook County Hosp, Chicago, Illinois 60612, United States
Univ of Chicago Children's Hosp, Chicago, Illinois 606371470, United States
Mt Sinai Hosp Med Ctr / Dept of Pediatrics, Chicago, Illinois 60608, United States
Tulane Univ / Charity Hosp of New Orleans, New Orleans, Louisiana 701122699, United States
Univ Hosp, New Orleans, Louisiana 70112, United States
Univ of Maryland at Baltimore / Univ Med Ctr, Baltimore, Maryland 21201, United States
Johns Hopkins Hosp - Pediatric, Baltimore, Maryland 212874933, United States
Children's Hosp of Boston, Boston, Massachusetts 021155724, United States
Boston City Hosp / Pediatrics, Boston, Massachusetts 02118, United States
Baystate Med Ctr of Springfield, Springfield, Massachusetts 01199, United States
Univ of Massachusetts Med School, Worcester, Massachusetts 016550001, United States
Children's Hosp of Michigan, Detroit, Michigan 48201, United States
Univ of Medicine & Dentistry of New Jersey / Univ Hosp, Newark, New Jersey 071032714, United States
Columbia Presbyterian Med Ctr, New York, New York 10032, United States
Bronx Lebanon Hosp Ctr, Bronx, New York 10457, United States
Univ of North Carolina at Chapel Hill / Duke Univ Med Ctr, Durham, North Carolina 27710, United States
Temple Univ School of Medicine, Philadelphia, Pennsylvania 191341095, United States
Saint Christopher's Hosp for Children, Philadelphia, Pennsylvania 191341095, United States
Med Univ of South Carolina, Charleston, South Carolina 294253312, United States
Children's Hospital & Medical Center / Seattle ACTU, Seattle, Washington 981050371, United States
Additional Information
Click here for more information about Zidovudine Click here for more information about Lamivudine Click here for more information about Nelfinavir mesylate Haga clic aquí para ver información sobre este ensayo clínico en español.
Related publications: Bryson Y, Stek A, Mirochnick M, et al. Pharmacokinetics, antiviral activity, and safety of nelfinavir (NFV) with ZDV/3TC in pregnant HIV-infected women and their infants. PACTG 353 cohort 2. 9th Conference on Retroviruses and Opportunistic Infections. 2002, February 24-28; Seattle Washington (abstract no 795)
Last updated: August 16, 2005
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