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

NCT ID: NCT00000865

Last Updated: 2021-10-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Completion Date: 1998-04-30

Brief Summary

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.

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.

Conditions

HIV Infections

Keywords

Drug Therapy, Combination; Reverse Transcriptase Inhibitors; Anti-HIV Agents

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Abacavir sulfate

Intervention Type: DRUG

Lamivudine

Intervention Type: DRUG

Stavudine

Intervention Type: DRUG

Zidovudine

Intervention Type: DRUG

Didanosine

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 3 Months
• Maximum Eligible Age: 13 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kline M

Role: STUDY_CHAIR

Van Dyke R

Role: STUDY_CHAIR

Yogev R

Role: STUDY_CHAIR

Shenep J

Role: STUDY_CHAIR

Locations

Usc La Nichd Crs

Los Angeles, California, United States

UCSD Maternal, Child, and Adolescent HIV CRS

San Diego, California, United States

Tulane/LSU Maternal/Child CRS

New Orleans, Louisiana, United States

Bronx-Lebanon Hosp. IMPAACT CRS

The Bronx, New York, United States

DUMC Ped. CRS

Durham, North Carolina, United States

St. Jude/UTHSC CRS

Memphis, Tennessee, United States

Texas Children's Hosp. CRS

Houston, Texas, United States

Countries

United States

References

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

Reference Type: BACKGROUND

Other Identifiers

11302

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 330

Identifier Type: -

Identifier Source: org_study_id