The Safety and Effectiveness of 1592U89 Plus 141W94 Plus DMP 266 in Patients With HIV Who Developed a Resistance to Protease Inhibitors

A Phase II Study Evaluating the Safety and Antiviral Activity of Combination Therapy With 1592U89, 141W94 and DMP 266 in HIV-1 Infected Subjects With Detectable HIV-1 Plasma RNA Despite Treatment With a Protease Inhibitor Containing Regimen

The purpose of this study is to see if it is safe and effective to give 1592U89 plus 141W94 plus DMP 266 to patients with HIV who have developed resistance to indinavir, ritonavir, saquinavir, or nelfinavir after at least 20 weeks of protease inhibitor treatment. This study also examines how long this combination therapy is effective before patients develop resistance to it.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Abacavir sulfate; Drug: Amprenavir; Drug: Efavirenz

Detailed Description

This is a multicenter, open-label study. A total of 80 patients are treated on this study and include:

At least 30 patients with a viral burden of 500 - 40,000 copies/ml. At least 30 patients with a viral burden greater than 40,000 copies/ml. At least 20 patients with less than 1 year total prior treatment with nucleoside reverse transcriptase inhibitors (NRTIs).

All patients receive self-administered, combination antiretroviral therapy for 48 weeks, as follows:

1592U89 plus 141W94 plus DMP 266.

• Study Type: Interventional
• Enrollment: 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Berkeley, California, United States, 94705
      • East Bay AIDS Ctr
    • Los Angeles, California, United States, 90036
      • Kraus Med Partners
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Univ Med School AIDS Treatment Unit
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Niaid / Nih
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Med Ctr
  • New York
    • New York, New York, United States, 10011
      • Saint Vincents Hosp / AIDS Ctr / 4th Floor
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27499
      • Univ of North Carolina Chapel Hill
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Univ Int Med Assoc Inc / Holmes Hosp / U of Cincinnati
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • The Miriam Hosp

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

Concurrent Medication:

Allowed:

• Hematologic supportive therapy with GM-CSF, G-CSF, or erythropoietin.
• Drugs that may interact with CYP3A4, that should be used with caution including (but not limited to):
• alprazolam, carbamazepine, codeine, cimetadine, clarithromycin, dapsone, diazepam, diltiazem, erythromycin, estrogens, fluvastatin, glucocorticoids, imipramine, itraconazole, ketoconazole, lidocaine, lovastatin, nifedipine, phenobarbital, phenytoin, quinidine, rifabutin, simvastatin, and warfarin.
• Detoxification treatment including opiate agonists (methadone, buprenorphine, etc.):
• Patients currently receiving this treatment should be enrolled only if stable on this therapy.

Patients must have:

• HIV-1 infection (all CDC clinical categories allowed).
• HIV-1 RNA greater than 500 copies/ml when measured on 1 occasion within 14 days of study drug administration.
• Signed, informed consent from parent or legal guardian for those patients under 18 years of age.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Malabsorption syndrome or other gastrointestinal dysfunction that may interfere with drug absorption or render the patient unable to take oral medication.
• Active AIDS-defining opportunistic infection or disease that is likely to preclude the patient from study participation.
• Serious medical conditions such as diabetes, congestive heart failure, cardiomyopathy, or other cardiac dysfunction that, in the opinion of the investigator, would compromise the safety of the patient.

Concurrent Medication:

Excluded:

• Immunomodulating agents, e.g., corticosteroids, interleukins, thalidomide, anti-cytokine agents and interferons.
• Cytotoxic chemotherapeutic agents (except local treatment for Kaposi's sarcoma).
• Anti-oxidants.
• Foscarnet therapy or therapy with other agents with documented activity against HIV-1 in vitro.
• Medications that interact with 141W94:
• terfenadine, astemizole, cisapride, triazolam, midazolam, and ergotamine/dihydroergotamine-containing regimens.
• Vitamin E supplements.
• Other investigational treatments (treatments available through Treatment IND or other expanded access mechanism evaluated on an individual basis).

Concurrent Treatment:

Excluded:

Anticipated need for radiation therapy (with the exception of local treatment for Kaposi's sarcoma).

Patients with the following symptoms and conditions are excluded:

• History of clinically relevant hepatitis within the previous six months.
• History of lymphoma.

Prior Medication:

Excluded:

• Cytotoxic chemotherapeutic agents within 30 days of study drug administration or an anticipated need for such treatment within the next 48 weeks (with exception of local treatment for Kaposi's sarcoma).
• Investigational HIV-1 vaccine trial and receipt of a dose of vaccine within the past 3 months.
• Immunomodulating agents such as systemic corticosteroids, interleukins, or interferons within 30 days of study drug administration.
• Exposure to the investigational agents 1592U89, 141W94, or DMP 266 (Sustiva).

Prior Treatment:

Excluded:

Radiation therapy.

Required:

• Treatment with at least 1 of the following protease inhibitors (PIs) for a minimum of 20 weeks prior to screening:

indinavir, ritonavir, saquinavir, and/or nelfinavir.

• Treatment with the same combination of PIs for the most recent 12 weeks and up through entry on study (Day 1).

Active alcohol or illicit drug use that is likely to interfere with dosing schedule compliance and protocol evaluations.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: Glaxo Wellcome

Study record dates

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): June 24, 2005
• Last Update Submitted That Met QC Criteria: June 23, 2005
• Last Verified: March 1, 1998

More Information

Terms related to this study

• Keywords: Drug Therapy, Combination; Anti-HIV Agents; HIV-1; RNA, Viral; Antiviral Agents; HIV Protease Inhibitors; VX 478; abacavir; efavirenz
• 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; 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; Protease Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; HIV Protease Inhibitors; Viral Protease Inhibitors; Antitubercular Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Efavirenz; Abacavir; Amprenavir
• Other Study ID Numbers: 264F; CNAA2007