A Study of 141W94 Used Alone or in Combination With Zidovudine Plus 3TC in HIV-Infected Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00001085
First received: November 2, 1999
Last updated: February 14, 2012
Last verified: February 2012
  Purpose

To determine the proportion of patients whose plasma HIV-1 RNA level remains below a detectable level (less than 500/ml) after 24 weeks of study therapy with either 141W94 monotherapy or 141W94 plus zidovudine (ZDV) and lamivudine (3TC). To determine the safety and tolerability of 141W94 monotherapy and the combination of 141W94 plus 3TC in patients with HIV infection.

Although dramatic inhibition of HIV-1 replication is achieved with ritonavir or indinavir monotherapy, in both cases maximum suppression required combination treatment together with nucleoside analog RT inhibitors. This study tests the hypothesis that monotherapy with 141W94 doses that result in Cmin levels far in excess of the IC90 corrected for plasma protein binding for HIV-1 can achieve the same virologic and immunologic effects in terms of magnitude and durability, as has been observed with combinations of other protease inhibitors plus nucleoside analogs.


Condition Intervention Phase
HIV Infections
Drug: Amprenavir
Drug: Lamivudine
Drug: Zidovudine
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Phase II Study of 141W94 (VX-478) Monotherapy vs. 141W94 (VX-478) Plus ZDV Plus 3TC in HIV Infected Individuals

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 94
Study Completion Date: September 1998
Detailed Description:

Although dramatic inhibition of HIV-1 replication is achieved with ritonavir or indinavir monotherapy, in both cases maximum suppression required combination treatment together with nucleoside analog RT inhibitors. This study tests the hypothesis that monotherapy with 141W94 doses that result in Cmin levels far in excess of the IC90 corrected for plasma protein binding for HIV-1 can achieve the same virologic and immunologic effects in terms of magnitude and durability, as has been observed with combinations of other protease inhibitors plus nucleoside analogs.

In this randomized, double-blind study, patients' HIV RNA is screened 30 days prior to entry. Patients satisfying enrollment criteria must have been on a stable antiretroviral regimen for 30 days prior to study screening and remain on the same regimen until entry. Patients are stratified based on the screening HIV-1 RNA copy number obtained within 30 days of entry: 5,000 - 50,000 copies/ml versus greater than 50,000 copies/ml. In addition, patients are stratified based on previous antiretroviral use: naive versus experienced. Patients are randomized to one of 2 treatment arms: Arm A - 141W94, plus Zidovudine (ZDV) and Lamivudine (3TC) or Arm B - 141W94, plus ZDV placebo and 3TC placebo.

[AS PER AMENDMENT 8/25/97: Patients assigned to the monotherapy arm are advised to discontinue their study medication immediately and initiate antiretroviral therapy with indinavir, nevirapine, stavudine and 3TC, as outlined in ACTG 347 roll-over protocol, ACTG 373. Patients in the three-drug arm continue on study therapy.] [AS PER AMENDMENT 12/19/97: Patients receive study treatment for 56 weeks and are followed through week 68.]

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Chemoprophylaxis for Pneumocystis carinii pneumonia is required for all patients who have a CD4 cell count <= 200 cells/mm3.
  • Topical and/or oral antifungal agents, except for those listed in excluded medications.
  • Treatment, maintenance or chemoprophylaxis with approved agents for opportunistic infections as clinically indicated, unless listed in excluded medications.
  • All antibiotics as clinically indicated.
  • Systemic corticosteroid use for <= 21 days for acute problems is permitted as medically indicated; chronic systemic corticosteroid use is not permitted.
  • Recombinant erythropoietin and granulocyte colony-stimulating factor as medically indicated.

Regularly prescribed medications such as:

  • antipyretics, analgesics, allergy medications, antidepressants, sleep medications, oral contraceptives (a barrier method is also required for this study), megestrol acetate, testosterone or any other medications, as medically indicated.
  • Alternative therapies such as vitamins, acupuncture and visualization techniques are permitted (excluding herbal medications).

NOTE:

  • Patients should report the use of these therapies; alternative therapies will be recorded.

Patients must have:

  • HIV-1 infection as documented by ELISA and confirmed.
  • >= 5,000 HIV-1 RNA copies/ml (within 30 days prior to study entry).
  • CD4 cell count >= 50 cells/mm3 within 60 days prior to study entry.
  • Signed, informed consent for patients < 18 years of age.

Prior Medication: Required:

  • Patients must be on a stable antiretroviral regimen for 30 days prior to study screening and remain on the same regimen until entry.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • Any active infection requiring acute treatment within 14 days prior to entry.
  • A malignancy that requires systemic therapy other than minimal Kaposi's sarcoma.

NOTE:

  • Patients with minimal Kaposi's sarcoma, defined as <= 5 cutaneous lesions and no visceral disease or tumor-associated edema, will be allowed to enroll as long as they do not require systemic therapy for Kaposi's sarcoma.

Patients with the following prior symptoms and conditions are excluded:

  • Inability to tolerate ZDV 500-600 mg daily if ZDV was administered previously. Intolerance to ZDV is defined as any grade toxicity that resulted in a dose reduction or termination of ZDV.

Prior Medication:

Excluded:

  • Any 3TC therapy prior to entry.
  • Any HIV-1 protease inhibitor therapy prior to study entry (e.g., saquinavir, ritonavir, indinavir, nelfinavir, 141W94).
  • Any immunomodulator therapy within 30 days prior to entry.
  • Active immunization within 30 days prior to entry.
  • Any antiretroviral therapy change within 30 days prior to study screening.

    1. Concurrent use of non-protocol specified antiretroviral agents; either investigational or licensed.

  • Immunomodulators that affect immunologic or virologic indices such as systemic corticosteroids, thalidomide, or cytokines.
  • Concomitant use of rifabutin and/or rifampin.
  • Investigational drugs other than 141W94/VX-478.
  • Systemic cytotoxic chemotherapy.
  • Oral astemizole (Hismanal), carbamazepine (Tegretol), dexamethasone (Decadron), ketoconazole (Nizoral), itraconazole (Sporanox), phenobarbital, phenytoin (Dilantin), terfenadine (Seldane), cisapride (Propulsid), triazolam (Halcion) and midazolam (Versed).
  • Herbal medications.
  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: NCT00001085

Locations
United States, Alabama
Alabama Therapeutics CRS
Birmingham, Alabama, United States, 35294
United States, California
USC CRS
Los Angeles, California, United States, 900331079
United States, Colorado
University of Colorado Hospital CRS
Aurora, Colorado, United States, 80262
United States, Florida
Univ. of Miami AIDS CRS
Miami, Florida, United States, 331361013
United States, Georgia
The Ponce de Leon Ctr. CRS
Atlanta, Georgia, United States, 30308
United States, Illinois
Northwestern University CRS
Chicago, Illinois, United States, 60611
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, United States, 60612
Cook County Hosp. CORE Ctr.
Chicago, Illinois, United States, 60612
United States, Massachusetts
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, United States, 02215
Bmc Actg Crs
Boston, Massachusetts, United States, 02118
United States, Missouri
St. Louis ConnectCare, Infectious Diseases Clinic
St Louis, Missouri, United States, 63112
Washington U CRS
St. Louis, Missouri, United States
United States, New York
NY Univ. HIV/AIDS CRS
New York, New York, United States, 10016
United States, North Carolina
Unc Aids Crs
Chapel Hill, North Carolina, United States, 275997215
United States, Pennsylvania
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Investigators
Study Chair: Murphy R
Study Chair: Gulick R
  More Information

Additional Information:
Publications:
Murphy R, Degruttola V, Gulick R, D'Aquila R, Eron J, Sommadossi JP, Smeaton L, Currier J, Tung R, Kuritzkes D. 141W94 with or without zidovudine/3TC in patients with no prior protease inhibitor or 3TC therapy-ACTG 347. Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:175 (abstract no 512)
Eron J, Smeaton L, Degruttola V, Schock J, Fiscus S, Tung R, Gulick R, Murphy R. The effects of amprenavir (APV) alone or in combination with ZDV/3TC, on HIV-1 levels in semen: a substudy of ACTG 347. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:109 (abstract no 222)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00001085     History of Changes
Other Study ID Numbers: ACTG 347, 11317
Study First Received: November 2, 1999
Last Updated: February 14, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
HIV-1
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
Zidovudine
HIV Protease Inhibitors
Lamivudine
RNA, Viral
VX 478
Reverse Transcriptase Inhibitors
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
Zidovudine
Lamivudine
Reverse Transcriptase Inhibitors
Amprenavir
HIV Protease Inhibitors
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents
Protease Inhibitors
Antibiotics, Antitubercular
Anti-Bacterial Agents
Antitubercular Agents

ClinicalTrials.gov processed this record on August 20, 2014