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

• Status: Completed
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

Summary

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).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: Bristol-Myers Squibb
• Treatments: Didanosine

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.