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

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Abacavir sulfate
Lamivudine
Stavudine
Zidovudine
Didanosine
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Drug Therapy, Combination, Reverse Transcriptase Inhibitors, Anti-HIV Agents

Eligibility Criteria

3 Months - 13 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Usc La Nichd Crs
  • UCSD Maternal, Child, and Adolescent HIV CRS
  • Tulane/LSU Maternal/Child CRS
  • Bronx-Lebanon Hosp. IMPAACT CRS
  • DUMC Ped. CRS
  • St. Jude/UTHSC CRS
  • Texas Children's Hosp. CRS

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 27, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00000865
Brief Title
The Safety and Effects of 1592U89 Used Alone or in Combination With Other Anti-HIV Drugs in HIV-Infected Infants and Children
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
April 1998 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
Drug Therapy, Combination, Reverse Transcriptase Inhibitors, Anti-HIV Agents

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Masking
None (Open Label)
Enrollment
32 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Abacavir sulfate
Intervention Type
Drug
Intervention Name(s)
Lamivudine
Intervention Type
Drug
Intervention Name(s)
Stavudine
Intervention Type
Drug
Intervention Name(s)
Zidovudine
Intervention Type
Drug
Intervention Name(s)
Didanosine

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Months
Maximum Age & Unit of Time
13 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kline M
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Van Dyke R
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Yogev R
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Shenep J
Official's Role
Study Chair
Facility Information:
Facility Name
Usc La Nichd Crs
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
UCSD Maternal, Child, and Adolescent HIV CRS
City
San Diego
State/Province
California
ZIP/Postal Code
920930672
Country
United States
Facility Name
Tulane/LSU Maternal/Child CRS
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
701122699
Country
United States
Facility Name
Bronx-Lebanon Hosp. IMPAACT CRS
City
Bronx
State/Province
New York
ZIP/Postal Code
10457
Country
United States
Facility Name
DUMC Ped. CRS
City
Durham
State/Province
North Carolina
ZIP/Postal Code
277103499
Country
United States
Facility Name
St. Jude/UTHSC CRS
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
381052794
Country
United States
Facility Name
Texas Children's Hosp. CRS
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

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

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