The Safety and Effectiveness of Clarithromycin Plus Zidovudine or Dideoxyinosine in the Treatment of Mycobacterium Avium Complex (MAC) Infections in Children With AIDS

A Phase I/II Dose-Ranging, Pharmacokinetic, Drug Interaction, Safety and Preliminary Efficacy Study of Oral Clarithromycin Granules for Suspension, in Combination With Zidovudine or Dideoxyinosine, in the Treatment of Disseminated Mycobacterium Avium Complex Infections in Pediatric Patients With AIDS

To evaluate three doses of clarithromycin in children with AIDS and Mycobacterium avium complex (MAC) infection who are receiving concurrent antiretroviral therapy.

Before more extensive evaluation of this promising drug for treatment of MAC infection in children can be done, it is important to study the pharmacokinetics of this drug in this population, to get information regarding its use in pediatric patients receiving currently available antiretroviral drugs, and to get information on the antimycobacterial activity of this drug.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Mycobacterium Avium-intracellulare Infection
• Intervention / Treatment: Drug: Zidovudine; Drug: Clarithromycin; Drug: Didanosine

Detailed Description

Before more extensive evaluation of this promising drug for treatment of MAC infection in children can be done, it is important to study the pharmacokinetics of this drug in this population, to get information regarding its use in pediatric patients receiving currently available antiretroviral drugs, and to get information on the antimycobacterial activity of this drug.

Patients that are included are HIV infected and have started zidovudine (AZT) or didanosine (ddI) at least 4 weeks before entry into this study. Patients continue taking the medications at prescribed doses. In addition they also take clarithromycin. Patients continue treatment with AZT or ddI plus clarithromycin for 12 weeks.

• Study Type: Interventional
• Enrollment: 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hosp of Los Angeles
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Natl Cancer Institute / HIV / AIDS Malignancy Branch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

Concurrent Medication:

Allowed:

• Prophylaxis treatment for Pneumocystis carinii pneumonia.
• Topical antivirals.

Prior Medication: Required:

• Zidovudine (AZT), 90 - 180 mg/m2 q6h, or didanosine (ddI), 60 - 120 mg/m2 q8h for 4 weeks prior to study entry.

Patients must have the following:

• Diagnosis of AIDS and Mycobacterium avium complex.
• Ability to tolerate therapy with zidovudine or didanosine at specified dosages.
• Written consent from a parent or legal guardian.
• Willing to comply with all procedures and scheduled visits. Relatively stable clinical condition.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

• History of significant depressive disorder.
• History of allergy to macrolide antibiotics.
• Presence of acute bacterial infection or acute onset of opportunistic infection as listed in protocol.

Patients with the following are excluded:

• Presence of current opportunistic infection other than Mycobacterium avium complex defined as systemic candidemia, cryptosporidiosis, isosporiasis, toxoplasmosis, pneumocystosis, salmonellosis, or acute bacterial infection.

Prior Medication:

Excluded within 30 days of study entry:

• Systemic antimycobacterial drugs, myelosuppressive drugs, nephrotoxic agents, cytotoxic or experimental chemotherapy, or antiviral drugs.

Active alcohol or drug use sufficient in the opinion of the investigator to prevent adequate compliance with medication regimen and clinic visits.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: Abbott
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Husson R

Publications and helpful links

General Publications

• Husson RN, Ross LA, Sandelli S, Inderlied CB, Venzon D, Lewis LL, Woods L, Conville PS, Witebsky FG, Pizzo PA. Orally administered clarithromycin for the treatment of systemic Mycobacterium avium complex infection in children with acquired immunodeficiency syndrome. J Pediatr. 1994 May;124(5 Pt 1):807-14. doi: 10.1016/s0022-3476(05)81380-0.

Study record dates

Study Major Dates

• Study Start: December 7, 2022
• Primary Completion: December 7, 2022
• Study Completion: December 7, 2022

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 (Estimate): August 4, 2008
• Last Update Submitted That Met QC Criteria: July 31, 2008
• Last Verified: October 1, 1996

More Information

Terms related to this study

• Keywords: Drug Therapy, Combination; Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Mycobacterium avium-intracellulare Infection; Didanosine; Drug Evaluation; Drug Interactions; Zidovudine
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections, Nontuberculous; Infections; Communicable Diseases; Mycobacterium Infections; Mycobacterium avium-intracellulare Infection; 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; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Zidovudine; Clarithromycin; Didanosine
• Other Study ID Numbers: ACTG 178; NCI 91 C-53

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No