A Phase I Trial to Evaluate Didanosine (ddI) in HIV-Infected Pregnant Women

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000839
First received: November 2, 1999
Last updated: March 28, 2012
Last verified: August 2004
  Purpose

To assess the pharmacokinetics, safety, and toxicity of intravenous and oral didanosine (ddI) administration in third trimester pregnant women who are HIV positive but are either intolerant or resistant to zidovudine (AZT). To collect data on infant toxicity following maternal treatment with ddI during the third trimester of pregnancy.

AZT may not be the optimal antiretroviral agent for all pregnant women requiring therapy for HIV infection. Although ddI has been approved for use in HIV-infected adults and older children, the safety and pharmacokinetics of ddI in pregnant women has not yet been determined.


Condition Intervention Phase
HIV Infections
Pregnancy
Drug: Didanosine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Primary Purpose: Treatment
Official Title: A Phase I Trial to Evaluate Didanosine (ddI) in HIV-Infected Pregnant Women

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 12
Study Completion Date: June 2001
Detailed Description:

AZT may not be the optimal antiretroviral agent for all pregnant women requiring therapy for HIV infection. Although ddI has been approved for use in HIV-infected adults and older children, the safety and pharmacokinetics of ddI in pregnant women has not yet been determined.

Patients receive a single IV dose of ddI on day 1 and pharmacokinetics values are determined. At least 48 hours but no more than 1 week after the IV dose, patients receive an oral dose, and oral pharmacokinetics are obtained for 8 hours. Oral ddI is then administered every 12 hours until labor commences and then after delivery, every 12 hours until 6 weeks postpartum. During labor and delivery, patients receive a loading dose of ddI followed by continuous infusion. Pharmacokinetics are obtained during infusion and also at 6 weeks postpartum. AS PER AMENDMENT 11/24/97: Maternal IV pharmacokinetic studies will not be performed after ddI IV formulation has expired (11/30/97). Maternal and cord samples will be required regardless of whether mother has received continuous IV ddI during labor.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Aerosolized pentamidine.
  • IV AZT during labor.

Patients must have:

  • HIV infection.
  • CD4 count > 50 and < 350 cells/mm3.
  • AZT intolerance or resistance.
  • Gestational age at least 26 weeks but not more than 36 weeks.
  • Consent of guardian if necessary. The father of the fetus must also provide consent if available after reasonable attempts have been made to contact him.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • Multiple gestation.
  • Current obstetrical complication, such as major anomalies, growth retardation, abnormal fluid level, fetal hydrops, or placental abruption (placenta previa is allowed).
  • No access to a participating ACTU.

Concurrent Medication:

Excluded:

  • Drugs that might aggravate pancreatitis, such as steroids, isoniazid, and parenteral pentamidine.
  • Antiretrovirals other than ddI (although IV AZT is allowed during labor).

Patients with the following prior conditions are excluded:

  • History of stillbirth, neonatal loss, or previous infant with anomaly (history of preeclampsia or preterm labor is permitted).
  • History of maternal medical complications including but not limited to malabsorption syndrome, pancreatitis, neurological complications including grade 2 or worse peripheral neuropathy, symptomatic cholelithiasis, or prior active CMV disease requiring ganciclovir or foscarnet.
  • History of poor medical compliance not related to access to medical care.

Prior Medication:

Excluded:

  • ddI within 24 hours prior to study entry.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000839

Locations
United States, California
UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS
Los Angeles, California, United States, 90095
UCSD Maternal, Child, and Adolescent HIV CRS
San Diego, California, United States, 92093
United States, Florida
Univ. of Florida Jacksonville NICHD CRS
Jacksonville, Florida, United States, 32209
Univ. of Miami Ped. Perinatal HIV/AIDS CRS
Miami, Florida, United States, 33161
United States, Illinois
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, United States, 60612
United States, Louisiana
Tulane/LSU Maternal/Child CRS
New Orleans, Louisiana, United States, 70112
Tulane Univ. Health Science Ctr., Tulane Univ. Hosp. & Clinic
New Orleans, Louisiana, United States, 70112
United States, New Jersey
NJ Med. School CRS
Newark, New Jersey, United States, 07103
United States, New York
Columbia IMPAACT CRS
New York, New York, United States, 10032
Incarnation Children's Ctr.
New York, New York, United States, 10032
United States, North Carolina
DUMC Ped. CRS
Durham, North Carolina, United States, 27710
Puerto Rico
Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS
San Juan, Puerto Rico, 00936
San Juan City Hosp. PR NICHD CRS
San Juan, Puerto Rico, 00936
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Chair: Livingston E
Study Chair: Bartlett JA
Study Chair: Unadkat J
  More Information

Additional Information:
Publications:
Livingston E, Patil S, Unadkat J, McKinney R, Abreu E, Bardequez A, O'Sullivan M. Placental transfer of didanosine (ddI) and initial evaluation of didanosine toxicity in HIV-1 infected pregnant women and their offspring. Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:121 (abstract no 226)
McKinney RE Jr. Ongoing and future trials of antiretroviral therapy in the pediatric AIDS clinical trials group (PACTG). Conf Retroviruses Opportunistic Infect. 1996 Jan 28-Feb 1;3rd:173
Patil SD, Livingston E, McKinney RE, Abreu E, O'Sullivan MJ, Bardequez A, Unadkat JD. Does pregnancy affect the pharmacokinetics of didanosine (ddI) in HIV-1 infected women? Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:121 (abstract no 225)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000839     History of Changes
Other Study ID Numbers: ACTG 249, 11226
Study First Received: November 2, 1999
Last Updated: March 28, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Pregnancy Trimester, Third
Pregnancy
Pregnancy Complications, Infectious
Didanosine
Acquired Immunodeficiency Syndrome
AIDS-Related Complex

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Didanosine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014