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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000839
• Other study ID #: ACTG 249
• Secondary ID: 11226
• Status: Completed
• Phase: Phase 1
• Est. completion date: June 2001

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: June 2001
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 13 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV Infections
• Pregnancy

Intervention

Drug:
• Didanosine

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (3)

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)