A Phase I Open-Label Study of the Safety, Tolerance, and Pharmacokinetic Interactions of Combination Didanosine and Ribavirin in HIV-Positive Individuals

• Status: Completed
• Trial end date: 1995-02-01
• Target enrollment: 0
• Participant gender: All

Summary

To evaluate the safety and tolerance of concurrent administration of standard-dose didanosine (ddI) with low-dose ribavirin in HIV-positive patients. To determine the pharmacokinetic interactions of concurrent administration of ddI and ribavirin and correlate pharmacokinetic parameters with toxicity. To investigate antiviral activity of the combined regimen.

Combination ddI/ribavirin therapy, if safe and effective, offers an alternative combination antiretroviral regimen for patients unable to tolerate regimens containing zidovudine (AZT).

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

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Bristol-Myers Squibb; ICN Pharmaceuticals
• Treatments: Didanosine; Ribavirin

Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

• Stable maintenance or prophylaxis therapy for opportunistic infection, if such therapy was administered for at least 30 days prior to study entry.

• Isoniazid for chemoprophylaxis against Mycobacterium tuberculosis.

• Fluconazole for mucosal candidiasis or cryptococcosis.

• Acyclovir (up to 1.0 g/day).

• Dapsone.

• Ketoconazole.

• Quinolones.

• Tetracycline.

• Vitamins and herbal therapies.

• Antibiotics as clinically indicated.

• Systemic corticosteroids for < 21 days for acute problems.

• Regularly prescribed medications.

Patients must have:

• HIV positivity by ELISA confirmed by Western blot.

• CD4 count < 500 cells/mm3 within 30 days prior to study entry.

• No active opportunistic infections requiring treatment (patients on stable maintenance and prophylaxis therapy for opportunistic infections for at least 30 days are permitted).

NOTE:

• Enrollment of women is encouraged.

Prior Medication:

Allowed:

• Prior stable maintenance or prophylaxis therapy for opportunistic infection, if administered for at least 30 days prior to study entry.

Exclusion Criteria

Concurrent Medication:

Excluded:

• Concurrent rifampin or rifabutin.

• Other anti-HIV drugs and investigational agents.

• Biological response modifiers.

• Ganciclovir or foscarnet.

• Systemic cytotoxic chemotherapy.

Concurrent Treatment:

Excluded:

• Concurrent radiation therapy other than limited localized therapy to the skin.

Patients with the following prior conditions are excluded:

• History of peripheral neuropathy.

• History of pancreatitis or active liver disease.

Prior Medication:

Excluded:

• Prior ddI.

• Ribavirin within 60 days prior to study entry.

• AZT or ddC within 2 weeks prior to study entry.

Prior Treatment:

Excluded:

• Transfusion within 2 weeks prior to study entry.

Active alcohol abuse.