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
Information source: NIH AIDS Clinical Trials Information Service
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections
Intervention: Indinavir sulfate (Drug); Levocarnitine (Drug); Adefovir dipivoxil (Drug); Lamivudine (Drug); Stavudine (Drug); Zidovudine (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: Gilead Sciences
Summary
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.
Clinical Details
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
Study design: Treatment, Safety Study
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
Minimum age: 16 Years.
Maximum age: N/A.
Gender(s): Both.
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.
Locations and Contacts
Hosp Regional de Ponce - Area Vieja, Ponce 00731, Puerto Rico
Phoenix Body Positive, Phoenix, Arizona 85016, United States
Davies Med Ctr, San Francisco, California 94114, United States
AIDS Healthcare Foundation Labs, Los Angeles, California 90027, United States
Blick Med Associates, Greenwich, Connecticut 06830, United States
George Washington Med Ctr, Washington, District of Columbia 20037, United States
Cook County Gen Hosp / Division of Infect Diseases, Chicago, Illinois 60612, United States
Johns Hopkins Univ School of Medicine, Baltimore, Maryland 21287, United States
Community Research Initiative, Brookline, Massachusetts 02445, United States
Community Research Initiative on AIDS, New York, New York 10001, United States
Saint Vincent's AIDS Ctr, New York, New York 10011, United States
Hershey Med Ctr / Dept of Hematology, Hershey, Pennsylvania 17033, United States
Mem Hosp of Rhode Island, Pawtucket, Rhode Island 02860, United States
Univ of Texas Southwestern Med Ctr of Dallas, Dallas, Texas 75235, United States
Swedish Med Ctr, Seattle, Washington 98122, United States
Additional Information
Last updated: June 23, 2005
|
