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

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000669
First received: November 2, 1999
Last updated: August 25, 2008
Last verified: October 1996
  Purpose

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).


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

Resource links provided by NLM:


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

Estimated Enrollment: 25
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.

  Eligibility

Ages Eligible for Study:   3 Months to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00000669

Locations
United States, Alabama
Univ of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Florida
Univ of Miami School of Medicine
Miami, Florida, United States, 331361013
United States, Tennessee
The Regional Medical Ctr, Memphis
Memphis, Tennessee, United States, 38105
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Univ TX Health Science Ctr
Houston, Texas, United States, 77030
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Chair: Scott GB
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00000669     History of Changes
Other Study ID Numbers: ACTG 091, 070V1, AI454-003
Study First Received: November 2, 1999
Last Updated: August 25, 2008
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Didanosine
Drug Evaluation
Acquired Immunodeficiency Syndrome
AIDS-Related Complex

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

ClinicalTrials.gov processed this record on July 24, 2014