Clinical trial NCT00000772: A Phase I Open-Label Study of the Safety, Tolerance, and Pharmacokinetic Interactions of Combination Didanosine and Ribavirin in HIV-Positive Individuals
Official title: A Phase I Open-Label Study of the Safety, Tolerance, and Pharmacokinetic Interactions of Combination Didanosine and Ribavirin in HIV-Positive Individuals
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: Ribavirin
Didanosine
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Bristol-Myers Squibb
name: ICN Pharmaceuticals
First posted: 2001-08-31
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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).

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.

Eligibility 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess - East Campus A0102 CRS
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota, ACTU
state: Minnesota
Study officials:
name: Japour AJ
role: STUDY_CHAIR
name: Lertora JJ
role: STUDY_CHAIR
name: Crumpacker C
role: STUDY_CHAIR
References:
citation: Japour AJ, et al. A Phase I study of the safety, tolerance, & pharmacokinetics of combination didanosine/ribavirin for HIV disease (ACTG 231). Natl Conf Hum Retroviruses Relat Infect (2nd). 1995 Jan 29-Feb 2:103