A Phase I Safety, Efficacy, and Pharmacokinetic Study of 2',3'-Dideoxyinosine (ddI) Administered Twice Daily to Patients With AIDS or AIDS Related Complex

• Status: Completed
• Trial end date: 1990-05-01
• Target enrollment: 0
• Participant gender: All

Summary

To determine the safety, pharmacokinetics (blood levels), and effectiveness of didanosine (ddI) when administered both intravenously and orally. After the maximum tolerated dose (MTD) is determined, an appropriate dosage regimen will then be established for Phase II and Phase III trials.

Zidovudine (AZT) has produced the best clinical results in the drug therapy of AIDS to date, but it produces toxicity in approximately 50 percent of patients. Early data show that ddI possesses high antiviral activity and less toxicity than AZT. The most effective route and dose of ddI has yet to be determined.

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

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Didanosine

Criteria

Inclusion Criteria

Concurrent Medication:

Recommended:

• Allopurinol for consistent occurrence of hyperuricemia observed with 2',3'-dideoxyinosine (ddI) administration.

Allowed:

• Aerosolized pentamidine for Pneumocystis carinii pneumonia (PCP) prophylaxis.

• Oral acyclovir for herpes simplex infections provided ddI dosing is suspended during this time.

• Ketoconazole for patients not responding to any other therapy and after consultation with the sponsor.

• Symptomatic therapy such as analgesics, antihistamines, antiemetics, antidiarrheal agents, or other supportive therapy may be administered as deemed necessary by the principal investigator.

• Aspirin rather than acetaminophen for fever.

Patients with the following will be included:

• An absence of life-threatening opportunistic infection on enrollment.

• A life expectancy less than 6 months.

• Available for follow-up for at least 6 months.

• Able to provide informed consent. Exclusion Criteria

Co-existing Condition:

Patients with the following are excluded:

• Intractable diarrhea.

• No venous access.

• A history of or propensity for seizure disorders.

• A history of past or current heart disease or other significant abnormality on routine EKG.

Concurrent Medication:

Excluded:

• Adenine deaminase inhibitors.

• Trimethoprim / sulfamethoxazole for Pneumocystis carinii pneumonia (PCP) infections.

• Antibiotics.

• Acetaminophen for therapy of fever.

Patients with the following are excluded:

• Intractable diarrhea.

• A life expectancy less than 6 months.

• No venous access.

• A history of or propensity for seizure disorders.

• A history of past or current heart disease or other significant abnormality on routine EKG.

Prior Medication:

Excluded:

• Any agent known as a potent inducer or inhibitor of drug-metabolizing enzymes.

• Excluded within 2 weeks of study entry:

• Trimethoprim / sulfamethoxazole.

• Excluded within 1 month of study entry:

• Any antiretroviral drug.

• Investigational agents.

• 2',3'-didanosine.

• AL721.

• Interferons.

• Immunomodulating drugs.

• Excluded within 3 months of study entry:

• Ribavirin.

• Cytotoxic agents.

Risk Behavior:

Excluded:

Active alcohol or drug abuse sufficient in the investigator's opinion to prevent adequate compliance.