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

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).

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Didanosine; Drug: Ribavirin

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 Type: Interventional
• Enrollment: 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess - East Campus A0102 CRS
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota, ACTU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Bristol-Myers Squibb; ICN Pharmaceuticals
• Investigators: Study Chair: Crumpacker C; Study Chair: Japour AJ; Study Chair: Lertora JJ

Publications and helpful links

General Publications

• 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

Study record dates

Study Major Dates

• Study Completion (Actual): February 1, 1995

Study Registration Dates

• First Submitted: November 2, 1999
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (Estimate): August 31, 2001

Study Record Updates

• Last Update Posted (Actual): October 28, 2021
• Last Update Submitted That Met QC Criteria: October 27, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Drug Therapy, Combination; Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Didanosine; Ribavirin
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; HIV Seropositivity; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Ribavirin; Didanosine
• Other Study ID Numbers: ACTG 231; 11208 (Registry Identifier: DAIDS ES Registry Number)