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
Didanosine
Blood-Borne Infections+14
+ Urogenital Diseases
+ Genital Diseases
Treatment Study
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 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.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.25 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.From 3 Months to 12 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
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.
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 5 locations
Univ of Alabama at Birmingham
Birmingham, United StatesOpen Univ of Alabama at Birmingham in Google MapsUniv of Miami School of Medicine
Miami, United StatesThe Regional Medical Ctr, Memphis
Memphis, United StatesBaylor College of Medicine
Houston, United States