A Phase I Safety and Pharmacokinetics Study of 2',3'-Dideoxyinosine (ddI) Administered Twice Daily to Infants and Children With AIDS or Symptomatic HIV Infection

August 25, 2008 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

To determine the safety and maximum tolerated dose (MTD) of 2',3'-dideoxyinosine (ddI), given orally and intravenously, in infants and children with AIDS. The study also measures bloodstream and cerebrospinal fluid (CSF) levels of the administered drug, and provides a preliminary assessment of the effectiveness of ddI on HIV replication.

AMENDED: Based on safety established in the first dosing phase of 52 weeks and long term dosing data in adults, the dosing period will be extended to 104 weeks. Original design: Information presently available indicates that ddI has high antiviral activity with less apparent toxicity than zidovudine (AZT) (the drug presently used to treat AIDS).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

AMENDED: Based on safety established in the first dosing phase of 52 weeks and long term dosing data in adults, the dosing period will be extended to 104 weeks. Original design: Information presently available indicates that ddI has high antiviral activity with less apparent toxicity than zidovudine (AZT) (the drug presently used to treat AIDS).

AMENDED: Dosing will proceed for 104 weeks at each dose level. Original design: Five patients are treated at the initial dose level. Because ddI is not stable in the acid environment of the stomach, oral doses of ddI follow administration of an antacid. An alternative method of dosing is to mix the reconstituted ddI with an appropriate volume of Maalox TC or Mylanta II. In order to determine the MTD, successive groups of 5 patients enter the study at a higher dose level after 3 patients have experienced 3 weeks of dosing and significant toxicities have not developed. Patients are assigned to treatment groups in the order in which they are enrolled. Dosing proceeds for 16 weeks at each dose level. However, consideration is given to escalating patients entered at the lowest dose to the next dose level after 10 weeks of dosing. The dose escalation continues until toxicities requiring dose modifications are found in 2 of 5 in any group.

Study Type

Interventional

Enrollment

25

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Univ of Alabama at Birmingham
    • Florida
      • Miami, Florida, United States, 331361013
        • Univ of Miami School of Medicine
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • The Regional Medical Ctr, Memphis
    • Texas
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine
      • Houston, Texas, United States, 77030
        • Univ TX Health Science Ctr

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 months to 12 years (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Aerosolized pentamidine for Pneumocystis carinii pneumonia (PCP) prophylaxis if this drug is extended to children.
  • Acute therapy not exceeding 7 days with oral or intravenous acyclovir for herpes simplex infections.
  • Trimethoprim / sulfamethoxazole for Pneumocystis carinii infections during course of study at discretion of investigator after discussion with the sponsor.
  • Symptomatic therapy with analgesics, antihistamines, antiemetics, antidiarrheal agents, or other supportive therapy as deemed necessary by the principal investigator.

Patients must have:

  • Diagnosis of AIDS as defined by CDC or meeting CDC P2 classification.
  • Patients must be free of opportunistic infection or other serious bacterial, fungal, or parasitic infection at time of entry into study.
  • Life expectancy > 6 months.
  • Parent or guardian (and patient as applicable) able to give informed consent.
  • Available for follow-up for at least 6 months.
  • Allowed: Hemophilia.

Exclusion Criteria

Co-existing Condition:

Children with the following are excluded:

  • Chronic hematologic disorders unrelated to coagulation defects, hemoglobinopathies, or ITP.
  • Intractable diarrhea.
  • No venous access.
  • History of seizures within previous 2 years or currently requiring anticonvulsants for control.
  • Currently active heart disease as evidenced by a cardiac arrhythmia or other significant abnormality on routine electrocardiography (ECG) or shortening fraction of < 10 percent on echocardiogram.
  • Renal disease.
  • Any other clinical condition that in the opinion of the investigator makes the patient unsuitable for study.

Concurrent Medication:

Excluded:

  • Antiretroviral drugs.
  • Zidovudine (AZT).
  • AL 721.
  • Interferon.
  • Corticosteroids.
  • Immunomodulating drugs.
  • Other systemic investigation agent.
  • Ribavirin.
  • Rifampin, barbiturates, or any other potent inducer or inhibitor of drug-metabolizing enzymes.
  • Cytotoxic anticancer therapy.
  • H-2 blockers.
  • Intravenous ketoconazole.
  • Immunoglobulin preparations.

Children with the following are excluded:

  • Chronic hematologic disorders unrelated to coagulation defects, hemoglobinopathies, or ITP.
  • Intractable diarrhea.
  • No venous access.
  • History of seizures within previous 2 years or currently requiring anticonvulsants for control.
  • Currently active heart disease as evidenced by a cardiac arrhythmia or other significant abnormality on routine electrocardiography (ECG) or shortening fraction of < 10 percent on echocardiogram.
  • Renal disease.
  • Any other clinical condition that in the opinion of the investigator makes the patient unsuitable for study.
  • Renal disease.

Prior Medication:

Excluded:

  • Any prior therapy which in the opinion of the investigator would make the patient unsuitable for study.

Excluded within 2 weeks of study entry:

  • Trimethoprim / sulfamethoxazole.

Excluded within 1 month of study entry:

  • Study drug or other antiretroviral drug or systemic investigational agent.
  • Any agent known as a potent inducer or inhibitor of drug metabolizing enzymes.
  • H-2 blockers.
  • Ketoconazole.
  • Immunoglobulin preparations.

Excluded within 3 months of study entry:

  • Ribavirin.

Excluded:

  • Zidovudine (AZT) for > 6 months.
  • Cytotoxic anticancer therapy.

Prior Treatment:

Excluded within 4 weeks of study entry:

  • Blood transfusion.
  • Lymphocyte transfusions for immune reconstitution.
  • Bone marrow transplant.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Masking: NONE

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Bristol-Myers Squibb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

First Submitted

November 2, 1999

First Submitted That Met QC Criteria

August 30, 2001

First Posted (ESTIMATE)

August 31, 2001

Study Record Updates

Last Update Posted (ESTIMATE)

August 26, 2008

Last Update Submitted That Met QC Criteria

August 25, 2008

Last Verified

October 1, 1996

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 091
  • 070V1
  • AI454-003

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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