A Study to Test the Safety, Tolerance, and Metabolism of Abacavir (1592U89, ABC) With Standard Zidovudine (ZDV) Therapy in Newborn Infants Born to HIV-1 Infected Women

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000864
First received: November 2, 1999
Last updated: May 17, 2012
Last verified: May 2012
  Purpose

The purpose of this study is to determine the safety, tolerance, and metabolism of single-dose and multiple-dose abacavir (ABC) in HIV-exposed infants receiving standard postnatal treatment with zidovudine (ZDV). This study also evaluates the correct dosages of ABC to be used in future studies.

Early aggressive therapy may be the best chance to slow disease progression in infants who may have been infected with HIV by their mothers. Early HIV suppression may significantly reduce viral levels and allow for restoration of the immune system, providing improved control over HIV infection. Therefore, it is important that the safety and tolerance of ABC in combination with ZDV be examined as potential early therapy in newborn and young infants.


Condition Intervention Phase
HIV Infections
Drug: Abacavir sulfate
Drug: Zidovudine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Primary Purpose: Treatment
Official Title: Phase I Study of Safety, Tolerance, and Pharmacokinetics of Abacavir (1592U89, ABC) With Standard Zidovudine (ZDV) Therapy In Neonates Born to HIV-1 Infected Women

Resource links provided by NLM:


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

Estimated Enrollment: 60
Study Completion Date: January 2001
Detailed Description:

The rationale for investigation of this agent is to define the safety and pharmacokinetics in young infants to allow for investigation of the efficacy of this agent in combination with ZDV as potential early therapy in newborn and young infants. The rationale for early aggressive therapy is that this may be the best chance to significantly reduce the long-term progression and subsequent impact of HIV-1 infection in vertically infected infants. Early ablation or enhanced suppression of HIV-1 replication may significantly reduce total viral load and may allow maturation, preservation, or reconstruction of immune function at a stage early in infection providing improved control of HIV-1 infection and reduced disease progression.

This study is divided into 3 sections, as follows: Part 1A is a single-dose study in neonates 0 to 72 hours of age. If four of four patients reach the minimal therapeutic level with less than Grade 3 toxicity, the ABC dose is escalated. Part 1B is also a single-dose study in infants 21 to 28 days of age, starting with the dose identified in Part 1A. If four of four patients reach the minimal therapeutic level with less than Grade 3 toxicity, the dose is escalated again. Finally, Part 2 is a multi-dose study to examine a dosing regimen for ABC and ZDV for neonates 0 to 72 hours of age. The dosing regimen for ABC is the dose defined in Part 1A for the first 3 weeks (0 to 3 weeks of age) followed by the dose defined in Part 1B for the second 3 weeks (3 to 6 weeks of age). All patients receive 6 weeks of standard ZDV therapy.

[AS PER AMENDMENT 9/24/97: This study is divided into sections, as follows: Part 1A is a single-dose study in neonates 0 to 48 hours of age. ABC dose escalations are made until a dose is identified that meets toxicity guidelines and demonstrates a minimal target area under the concentration curve (AUC) of 2,000 ng-hr/ml. Part 1B is a similar single-dose study in infants 3 to 7 days of age with escalation as per part 1A. Part 1C is an identical single-dose study in infants 21 to 28 days of age but starting at the dose identified in Part 1B. Part 2 is a multi-dose study to examine a 6-week dosing regimen for ABC and ZDV for infants 0 to 48 hours of age. The dosing regimen for ABC is defined in Part 1A for the first 48 hours of life, the dose defined in Part 1B for Days 3 through 20 of life, and the dose defined in Part 1C for Days 21 through 42 of life.] [AS PER AMENDMENT 7/29/98: Enrollment to Parts 1A and 1B will remain open; Part 1A will enroll a minimum of 4 patients as planned, and Part 1B will enroll 3 additional patients.]

  Eligibility

Ages Eligible for Study:   up to 28 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Infants may be eligible for this study if they:

  • Are between birth and 48 hours of age, between 3 and 7 days of age, or between 21 and 28 days of age.
  • Have no serious infections requiring treatment during the study period.
  • Are receiving ZDV therapy.
  • Can tolerate oral feeding.
  • Are born to HIV-positive mothers whose pregnancy lasted at least 37 weeks.

Exclusion Criteria

Infants will not be eligible for this study if they:

  • Have a major congenital abnormality.
  • Have a serious laboratory or clinical toxicity at time of study entry.
  • Previously enrolled in Part 1 of this study.
  • Are unable to be followed for the duration of this study.
  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: NCT00000864

Locations
United States, Alabama
UAB, Dept. of Ped., Div. of Infectious Diseases
Birmingham, Alabama, United States, 35233
United States, California
UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS
Los Angeles, California, United States, 900951752
Usc La Nichd Crs
Los Angeles, California, United States, 90033
UCSD Maternal, Child, and Adolescent HIV CRS
San Diego, California, United States
United States, Florida
Univ. of Florida Jacksonville NICHD CRS
Jacksonville, Florida, United States, 32209
United States, Georgia
Emory Univ. School of Medicine, Dept. of Peds., Div. of Infectious Diseases
Atlanta, Georgia, United States, 30306
United States, Illinois
Univ. of Illinois College of Medicine at Chicago, Dept. of Peds.
Chicago, Illinois, United States, 60612
United States, Massachusetts
HMS - Children's Hosp. Boston, Div. of Infectious Diseases
Boston, Massachusetts, United States, 021155724
United States, New York
Bronx-Lebanon Hosp. IMPAACT CRS
Bronx, New York, United States, 10457
SUNY Upstate Med. Univ., Dept. of Peds.
Syracuse, New York, United States, 13210
United States, North Carolina
DUMC Ped. CRS
Durham, North Carolina, United States, 277103499
United States, South Carolina
Med. Univ. of South Carolina, Div. of Ped. Infectious Diseases
Charleston, South Carolina, United States, 294253312
Puerto Rico
San Juan City Hosp. PR NICHD CRS
San Juan, Puerto Rico, 009367344
Sponsors and Collaborators
Investigators
Study Chair: George Johnson
Study Chair: Andrew Wiznia
  More Information

Additional Information:
Publications:
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

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000864     History of Changes
Other Study ID Numbers: ACTG 321, 11295, PACTG 321
Study First Received: November 2, 1999
Last Updated: May 17, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Pregnancy
Pregnancy Complications, Infectious
HIV-1
Drug Therapy, Combination
Zidovudine
Drug Administration Schedule
Disease Transmission, Vertical
Reverse Transcriptase Inhibitors
Anti-HIV Agents

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

ClinicalTrials.gov processed this record on July 20, 2014