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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00000772

Collaborator

Bristol-Myers Squibb (Industry), ICN Pharmaceuticals (Industry)

Enrollment

Locations

7.5

Patients Per Site

Study Details

Study Description

Brief 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).

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Ribavirin Drug: Didanosine	Phase 1

Detailed Description

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

Patients receive ddI alone for 4 weeks, followed by 8 weeks of combination ddI/ribavirin. Patients who complete the first 12 weeks without major toxicity may receive an additional 12 weeks of combination therapy on an optional basis. Patients are followed for 60 days after the last treatment visit.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Completion Date :

Feb 1, 1995

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beth Israel Deaconess - East Campus A0102 CRS	Boston	Massachusetts	United States	02215
2	University of Minnesota, ACTU	Minneapolis	Minnesota	United States	55455