The Safety and Effects of 1592U89 Used Alone or in Combination With Other Anti-HIV Drugs in HIV-Infected Infants and Children

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000865
First received: November 2, 1999
Last updated: February 14, 2012
Last verified: February 2012
  Purpose

To assess the steady state pharmacokinetic features, tolerance, and safety of orally administered 1592U89, given alone or in combination with other antiretroviral medications, in HIV infected infants and children. To establish doses of 1592U89 appropriate for future pediatric Phase II/III clinical trials.

On the basis of the preclinical and clinical studies, 1592U89 appears to be a promising agent for treatment of HIV infection in children, either as an alternative to currently employed agents, or in combination therapy regimens. A liquid formulation of the drug is available; thus concurrent development of 1592U89 for children and adults is possible.


Condition Intervention Phase
HIV Infections
Drug: Abacavir sulfate
Drug: Lamivudine
Drug: Stavudine
Drug: Zidovudine
Drug: Didanosine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Safety and Pharmacokinetic Study of 1592U89 Alone and In Combination With Other Antiretroviral Agents in Infants and Children With HIV Infection

Resource links provided by NLM:


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

Estimated Enrollment: 32
Study Completion Date: April 1998
Detailed Description:

On the basis of the preclinical and clinical studies, 1592U89 appears to be a promising agent for treatment of HIV infection in children, either as an alternative to currently employed agents, or in combination therapy regimens. A liquid formulation of the drug is available; thus concurrent development of 1592U89 for children and adults is possible.

In part 1, patients will receive 1592U89 monotherapy for 12 weeks. Patients will be assigned initially to a low dose of 1592U89 (Dose A). Those patients who tolerate the drug for at least six weeks without a toxicity of grade 3 or above attributable to study drug will have their 1592U89 dose increased (Dose B). If none of those patients experience a life threatening event attributable to study drug, subsequent enrollees will be assigned initially to Dose B. In part 2, each participant will be assigned randomly (1:1:1:1) within their age and Part 1 regimen stratum to one of the four agents: Zidovudine (ZDV), Stavudine (d4T), Didanosine (ddI) or Lamivudine (3TC) in combination with 1592U89.

  Eligibility

Ages Eligible for Study:   3 Months to 13 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

  • IVIG.
  • Erythropoietin, granulocyte colony stimulating factor and granulocyte macrophage colony stimulating factor (for management of hematologic toxicity).

Patients must have:

  • Documented HIV-1 infection.
  • Laboratory evidence of immunosuppression or symptomatic HIV disease.
  • Parent or legal guardian able and willing to provide signed informed consent.

Prior Medication: Required:

  • HIV infected infants and children will be eligible for the trial if they have received greater than 56 days of previous antiretroviral therapy.

NOTE:

  • Those children who participated in the single dose phase I study of 1592U89 and satisfy all other criteria for inclusion may have received <= 56 days of previous antiretroviral therapy.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

  • Grade 3 or greater abnormalities in any toxicity monitoring laboratory tests at baseline.
  • Presence of an acute opportunistic infection requiring therapy at the time of enrollment.
  • Intractable or chronic diarrhea or vomiting.

Concurrent Medication:

Excluded:

  • Chemotherapy for active malignancy.
  • Concurrent use of antiretroviral agents other than those provided by the study, biologic response modifiers, human growth hormone, systemic corticosteroids (>= 14 days duration), probenecid, I.V. pentamidine, immunomodulators (other than intravenous immunoglobulin), or other investigational drugs.

Patients with any of the following prior conditions or symptoms are excluded:

- History of intolerance to any of the study drugs.

  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: NCT00000865

Locations
United States, California
Usc La Nichd Crs
Los Angeles, California, United States, 90033
UCSD Maternal, Child, and Adolescent HIV CRS
San Diego, California, United States, 920930672
United States, Louisiana
Tulane/LSU Maternal/Child CRS
New Orleans, Louisiana, United States, 701122699
United States, New York
Bronx-Lebanon Hosp. IMPAACT CRS
Bronx, New York, United States, 10457
United States, North Carolina
DUMC Ped. CRS
Durham, North Carolina, United States, 277103499
United States, Tennessee
St. Jude/UTHSC CRS
Memphis, Tennessee, United States, 381052794
United States, Texas
Texas Children's Hosp. CRS
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Study Chair: Kline M
Study Chair: Van Dyke R
Study Chair: Yogev R
Study Chair: Shenep J
  More Information

Additional Information:
Publications:
Hughes W, McDowell J, L Adams, Flynn P, Hetherington S, Kline M, Shenep J, Yogev R, Lafon S. Evaluation of the novel nucleoside 1592U89 in a phase I safety and pharmacokinetics (PK) study in HIV-infected infants and children. Conf Retroviruses Opportunistic Infect. 1996 Jan 28-Feb 1;3rd:115

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000865     History of Changes
Other Study ID Numbers: ACTG 330, 11302
Study First Received: November 2, 1999
Last Updated: February 14, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Drug Therapy, Combination
Reverse Transcriptase Inhibitors
Anti-HIV Agents

Additional relevant MeSH terms:
Infection
Communicable Diseases
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
Reverse Transcriptase Inhibitors
Abacavir
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on September 16, 2014