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

Launched by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) · Aug 30, 2001

Keywords

ClinConnect Summary

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 ant...

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Eligibility 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.