The Safety and Effectiveness of Adefovir Dipivoxil Plus Indinavir Combined With Zidovudine or Lamivudine or Stavudine in HIV-Infected Patients Who Have Not Taken Anti-HIV Drugs

This study has been completed.
Sponsor:
Information provided by:
NIH AIDS Clinical Trials Information Service
ClinicalTrials.gov Identifier:
NCT00002379
First received: November 2, 1999
Last updated: June 23, 2005
Last verified: October 1998
  Purpose

To evaluate the safety and tolerance of adefovir dipivoxil and indinavir administered orally in combination with zidovudine, lamivudine, or stavudine in HIV-infected patients with CD4 cell counts >= 100 cells/mm3 and an HIV-1 RNA baseline copy number >= 5000 copies/ml. To determine the proportion of patients whose plasma HIV-1 RNA level falls below the level of detection (500 copies/ml) by 20 weeks of study therapy and the average reduction in HIV-1 RNA from baseline through study week 20. To evaluate the durability of the antiviral response through 48 weeks of study in patients who continue on study therapy after week 24.


Condition Intervention Phase
HIV Infections
Drug: Indinavir sulfate
Drug: Levocarnitine
Drug: Adefovir dipivoxil
Drug: Lamivudine
Drug: Stavudine
Drug: Zidovudine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Primary Purpose: Treatment
Official Title: A Phase II, Stratified, Randomized, Open-Label, Multi-Center Study of the Safety and Efficacy of Adefovir Dipivoxil and Indinavir in Combination With Zidovudine, Lamivudine, or Stavudine for the Treatment of Therapy Naive HIV-Infected Patients With CD4 Cell Counts >= 100 Cells/mm3 and HIV-1 RNA Copy Numbers >= 5,000 Copies/Ml

Resource links provided by NLM:


Further study details as provided by NIH AIDS Clinical Trials Information Service:

Estimated Enrollment: 100
Detailed Description:

This protocol is a stratified, randomized, open-label study of the safety and efficacy of adefovir dipivoxil with indinavir as quadruple therapy in combination with zidovudine and lamivudine, or as triple combination administered with either zidovudine or lamivudine or stavudine for 48 weeks in the treatment of HIV-infected patients with CD4 cell counts >= 100/mm3 and an HIV-1 RNA baseline copy number >= 5000 copies/ml. Patients will be randomized to adefovir dipivoxil, indinavir, zidovudine, and lamivudine or adefovir dipivoxil, indinavir, and a nucleoside inhibitor (randomly assigned to receive zidovudine, lamivudine, or stavudine) or to indinavir, zidovudine, and lamivudine. Additionally, a daily dose of L-carnitine will be administered to all patients randomized to an arm containing adefovir dipivoxil.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Patients must have:

  • Laboratory diagnosis of HIV infection (positive HIV antibody test confirmed by Western blot, p24 antigen assay, HIV-1 RNA, or HIV-1 culture).
  • An HIV-1 RNA plasma titer >= 5000 copies/ml within 14-21 days prior to the baseline visit.
  • CD4 cell count >= 100 cells/mm3 within 14-21 days prior to the baseline visit.
  • A minimum life expectancy of at least 1 year.
  • Signed, informed consent from parent or legal guardian for those patients < 18 years of age.

Exclusion Criteria

Co-existing Condition:

Patients with any of the following symptoms and conditions are excluded:

  • Active, serious infections (other than HIV infection) requiring parenteral antibiotic or antiviral therapy. Patients will be considered recovered from such infectious episodes if at least 2 weeks elapsed following the cessation of parenteral therapy before the baseline visit.
  • Exhibiting evidence of a gastrointestinal malabsorption syndrome or chronic nausea or vomiting which may confer an inability to receive an orally administered medication.
  • Malignancy other than cutaneous Kaposi's sarcoma (KS) or basal cell carcinoma. Patients with biopsy-confirmed cutaneous KS are eligible, but must not have received any systemic therapy for KS within 4 weeks prior to baseline and are not anticipated to require systemic therapy during the study.
  • Any other clinical condition that in the opinion of the investigator would make the patient unsuitable for study or unable to comply with the dosing requirements.

Patients with any of the following prior conditions are excluded:

  • A new AIDS-defining event diagnosed within 1 month prior to baseline.
  • Any patient who has previously been discontinued from zidovudine, lamivudine, and/or stavudine due to a drug-related toxicity.
  • Significant history of peripheral neuropathy.

    1. Treatment with immunomodulating agents such as systemic corticosteroids, IL-2, or interferons.

  • Saquinavir, ritonavir, nelfinavir, nevirapine, delavirdine, didanosine, dideoxycytidine, interferon alpha, interferon beta, isoniazid, rifampin, investigational agents (except upon Sponsor approval), chemotherapeutic agents (systemic), terfenadine, astemizole, cisapride, triazolam, and midazolam.

    1. Prior use of adefovir dipivoxil.

  • Prior non-protease antiretroviral therapy (other than antiretroviral vaccines) for greater than 4 cumulative weeks.
  • Prior use of any antiretroviral protease inhibitor.
  • Immunizations within 30 days of baseline.
  • Antiretroviral vaccine therapy within 60 days of baseline.
  • Treatment in the 4 weeks prior to baseline, with immunomodulating agents such as systemic corticosteroids, IL-2, or interferons.
  • Any other investigational drug within 30 days prior to baseline.
  • Any prior therapy that, in the opinion of the investigator, would make the patient unsuitable for study or unable to comply with the dosing requirements.

Patients with current alcohol or substance abuse judged by the investigator to potentially interfere with patient compliance.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002379

Locations
United States, Arizona
Phoenix Body Positive
Phoenix, Arizona, United States, 85016
United States, California
AIDS Healthcare Foundation Labs
Los Angeles, California, United States, 90027
Davies Med Ctr
San Francisco, California, United States, 94114
United States, Connecticut
Blick Med Associates
Greenwich, Connecticut, United States, 06830
United States, District of Columbia
George Washington Med Ctr
Washington, District of Columbia, United States, 20037
United States, Illinois
Cook County Gen Hosp / Division of Infect Diseases
Chicago, Illinois, United States, 60612
United States, Maryland
Johns Hopkins Univ School of Medicine
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Community Research Initiative
Brookline, Massachusetts, United States, 02445
United States, New York
Community Research Initiative on AIDS
New York, New York, United States, 10001
Saint Vincent's AIDS Ctr
New York, New York, United States, 10011
United States, Pennsylvania
Hershey Med Ctr / Dept of Hematology
Hershey, Pennsylvania, United States, 17033
United States, Rhode Island
Mem Hosp of Rhode Island
Pawtucket, Rhode Island, United States, 02860
United States, Texas
Univ of Texas Southwestern Med Ctr of Dallas
Dallas, Texas, United States, 75235
United States, Washington
Swedish Med Ctr
Seattle, Washington, United States, 98122
Puerto Rico
Hosp Regional de Ponce - Area Vieja
Ponce, Puerto Rico, 00731
Sponsors and Collaborators
Gilead Sciences
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00002379     History of Changes
Other Study ID Numbers: 232D
Study First Received: November 2, 1999
Last Updated: June 23, 2005
Health Authority: United States: Food and Drug Administration

Keywords provided by NIH AIDS Clinical Trials Information Service:
HIV-1
Drug Therapy, Combination
Administration, Oral
Acquired Immunodeficiency Syndrome
Zidovudine
Stavudine
HIV Protease Inhibitors
CD4 Lymphocyte Count
Lamivudine
Indinavir
RNA, Viral
Adenine
Anti-HIV Agents
Viral Load

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Lamivudine
Zidovudine
Stavudine
Adefovir
Adefovir dipivoxil
Indinavir
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents
Antimetabolites
HIV Protease Inhibitors
Protease Inhibitors

ClinicalTrials.gov processed this record on September 22, 2014