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
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

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.]
    

Intervention name(s): Abacavir sulfate; Zidovudine
Intervention type(s): Drug; Drug
Intervention MeSH terms: Zidovudine; Abacavir
Primary purpose: Treatment
Keywords: Pregnancy; Pregnancy Complications, Infectious; HIV-1; Drug Therapy, Combination; Zidovudine; Drug Administration Schedule; Disease Transmission, Vertical; Reverse Transcriptase Inhibitors; Anti-HIV Agents