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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Pregnancy
• Intervention / Treatment: Drug: Didanosine

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.

• Study Type: Interventional
• Enrollment: 12
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Bristol-Myers Squibb
• Investigators: Study Chair: Livingston E; Study Chair: Unadkat J

Publications and helpful links

General 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)

Study record dates

Study Major Dates

• Study Start: December 7, 2022
• Primary Completion: December 7, 2022
• Study Completion (Actual): June 1, 2001

Study Registration Dates

• First Submitted: November 2, 1999
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (Estimate): August 31, 2001

Study Record Updates

• Last Update Posted (Actual): October 29, 2021
• Last Update Submitted That Met QC Criteria: October 27, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Pregnancy; Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Didanosine; Pregnancy Trimester, Third; Pregnancy Complications, Infectious
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Didanosine
• Other Study ID Numbers: ACTG 249; 11226 (Registry Identifier: DAIDS ES Registry Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No