A Study on Amprenavir in Combination With Other Anti-HIV Drugs in HIV-Positive Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000912
First received: November 2, 1999
Last updated: July 26, 2013
Last verified: July 2013
  Purpose

The purpose of this study is to compare 4 different combinations of anti-HIV drugs and to determine the number of people whose HIV blood levels decrease to 200 copies/ml or less while on the treatment. This study evaluates the safety of these drug combinations, which include an experimental protease inhibitor (PI), amprenavir.

Despite the success that many patients have had with PI treatment regimens, there is still a possibility that patients receiving PIs may continue to have high HIV blood levels. Because of this possibility, alternative drug combinations containing PIs are being studied. It appears that amprenavir, when taken with 3 or 4 other anti-HIV drugs, may be effective in patients with prior PI treatment experience.


Condition Intervention Phase
HIV Infections
Drug: Indinavir sulfate
Drug: Abacavir sulfate
Drug: Amprenavir
Drug: Nelfinavir mesylate
Drug: Efavirenz
Drug: Levocarnitine
Drug: Adefovir dipivoxil
Drug: Saquinavir
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Primary Purpose: Treatment
Official Title: A Phase II, Randomized Trial of Amprenavir as Part of Dual Protease Inhibitor Regimens (Placebo-Controlled) in Combination With Abacavir, Efavirenz, and Adefovir Dipivoxil Versus Amprenavir Alone in HIV-Infected Subjects With Prior Exposure to Approved Protease Inhibitors and Loss of Virologic Suppression as Reflected by a Plasma HIV-1 RNA Concentration >= 1,000 Copies/ml

Resource links provided by NLM:


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

Estimated Enrollment: 475
Study Completion Date: May 2000
Detailed Description:

A number of studies both within and outside the ACTG have been initiated or are in development to try to address the issue of alternative treatments for patients who either do not achieve or lose virologic control while receiving protease inhibitors (PIs). Amprenavir (APV) is an attractive candidate to investigate as part of salvage regimens because: 1) it has substantial antiretroviral activity; 2) there are preliminary in vitro and in vivo data that suggest that resistance to this agent may be mediated in part by a unique mutation (I50V); and 3) its cross-resistance profile to the approved PIs is uncertain.

Patients are selectively randomized to 1 of 4 study arms based on prior PI experience. Those randomized to Arms A, B, or C receive 2 PIs, 1 of which is amprenavir (APV), and those randomized to Arm D receive a single PI (APV) as part of their treatment regimen, as follows:

Arm A: APV plus saquinavir soft gel capsule (SQVsgc) plus abacavir (ABC) plus efavirenz (EFV) plus adefovir (ADV).

Arm B: APV plus indinavir (IDV) plus ABC plus EFV plus ADV. Arm C: APV plus nelfinavir (NFV) plus ABC plus EFV plus ADV. Arm D: APV plus placebo (NFV, IDV, or SQVsgc) plus ABC plus EFV plus ADV. All patients receive L-carnitine supplementation. All patients receive clinical physical assessments and laboratory testing during study as follows: Weeks 2, 4, and every 4 weeks thereafter. A primary analysis is performed after the last patient has reached 24 weeks. [AS PER AMENDMENT 3/2/00: At that time, all patients are unblinded to their original treatment assignment.] Patients who experience virologic failure are unblinded and may choose 1 of the following 3 options: Continue study medications open-label, permanently discontinue study medications, or selectively continue study medications [AS PER AMENDMENT 3/2/00: from the arm the patient was originally randomized to] and combine with other approved antiretroviral agents. [AS PER AMENDMENT 3/2/00: For patients adding didanosine (ddI) to their regimens, monitoring for the development of pancreatitis is crucial.] Final evaluations are required for those patients who are off drug during the immediate 8-week period following the last dose of study treatment. Beyond 8 weeks, they are followed for incidence of death, cancer, congenital anomalies, and permanent disabilities. [AS PER AMENDMENT 3/2/00: Gilead Sciences has terminated its U.S. development of ADV for HIV infection. Gilead will continue to supply ADV for patients in ACTG 398 until the study closes. Patients who are receiving ADV at the completion of the study may continue to access ADV through the Expanded Access Program, provided that the physician and patient have determined that continued use of ADV is beneficial.]

  Eligibility

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

Inclusion Criteria

Patients may be eligible for this study if they:

  • Are HIV-positive.
  • Have current virologic failure (2 consecutive HIV blood levels above 1,000 copies/ml) while on PIs.
  • Are over 13 years of age (consent of parent or guardian required if under 18).
  • Agree to practice abstinence or use effective methods of birth control during the study and for 90 days after.

Exclusion Criteria

Patients will not be eligible for this study if they:

  • Have hepatitis within 90 days prior to study entry.
  • Have a history of a peripheral neuropathy within 60 days of study entry.
  • Have an unexplained temperature for a 7-day period.
  • Have chronic diarrhea within 30 days prior to study entry.
  • Have cancer requiring chemotherapy.
  • Received any therapy for infection or other illness within 30 days prior to study entry.
  • Have received certain other medications.
  • Are pregnant or breast-feeding.
  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: NCT00000912

  Hide Study Locations
Locations
United States, California
UCLA CARE Ctr
Los Angeles, California, United States, 90095
USC Univ Hosp & Ambulatory Hlth Care Ctr / USC Med Ctr
Los Angeles, California, United States, 900334508
Univ of Southern California / LA County USC Med Ctr
Los Angeles, California, United States, 900331079
Willow Clinic
Menlo Park, California, United States, 94025
Univ of California / San Diego Treatment Ctr
San Diego, California, United States, 921036325
San Francisco Gen Hosp
San Francisco, California, United States, 941102859
San Francisco AIDS Clinic / San Francisco Gen Hosp
San Francisco, California, United States, 941102859
Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
San Jose, California, United States, 951282699
Stanford Univ Med Ctr
Stanford, California, United States, 943055107
San Mateo AIDS Program / Stanford Univ
Stanford, California, United States, 943055107
United States, Colorado
Univ of Colorado Health Sciences Ctr
Denver, Colorado, United States, 80262
United States, District of Columbia
Howard Univ
Washington, District of Columbia, United States, 20059
United States, Florida
Univ of Miami School of Medicine
Miami, Florida, United States, 331361013
United States, Georgia
Emory Univ
Atlanta, Georgia, United States, 30308
Emory Hemo Comp Evaluation Clinic / East TN Comp Hemo Ctr
Atlanta, Georgia, United States, 303652225
United States, Hawaii
Queens Med Ctr
Honolulu, Hawaii, United States, 96816
Univ of Hawaii
Honolulu, Hawaii, United States, 96816
Tripler Army Med Ctr
Tripler AMC, Hawaii, United States, 96859
United States, Illinois
Northwestern Univ Med School
Chicago, Illinois, United States, 60611
Rush Presbyterian - Saint Luke's Med Ctr
Chicago, Illinois, United States, 60612
Cook County Hosp
Chicago, Illinois, United States, 60612
United States, Louisiana
Charity Hosp / Tulane Univ Med School
New Orleans, Louisiana, United States, 70112
Tulane Univ School of Medicine
New Orleans, Louisiana, United States, 70112
United States, Maryland
Johns Hopkins Hosp
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Harvard (Massachusetts Gen Hosp)
Boston, Massachusetts, United States, 02114
Boston Med Ctr
Boston, Massachusetts, United States, 02118
United States, Minnesota
Univ of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
St Louis Regional Hosp / St Louis Regional Med Ctr
St Louis, Missouri, United States, 63112
United States, New York
SUNY / Erie County Med Ctr at Buffalo
Buffalo, New York, United States, 14215
Mem Sloan - Kettering Cancer Ctr
New York, New York, United States, 10021
Bellevue Hosp / New York Univ Med Ctr
New York, New York, United States, 10016
Mount Sinai Med Ctr
New York, New York, United States, 10029
Cornell Univ Med Ctr
New York, New York, United States, 10021
Chelsea Ctr
New York, New York, United States, 10021
Univ of Rochester Medical Center
Rochester, New York, United States, 14642
United States, North Carolina
Duke Univ Med Ctr
Durham, North Carolina, United States, 27710
Moses H Cone Memorial Hosp
Greensboro, North Carolina, United States, 27401
United States, Ohio
Univ of Cincinnati
Cincinnati, Ohio, United States, 452670405
Ohio State Univ Hosp Clinic
Columbus, Ohio, United States, 432101228
United States, Pennsylvania
Milton S Hershey Med Ctr
Hershey, Pennsylvania, United States, 170330850
Univ of Pennsylvania at Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Univ of Pittsburgh Med Ctr
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
Univ of Texas Galveston
Galveston, Texas, United States, 775550435
United States, Washington
Univ of Washington
Seattle, Washington, United States, 981224304
Puerto Rico
Univ of Puerto Rico
San Juan, Puerto Rico, 009365067
Sponsors and Collaborators
Investigators
Study Chair: Scott Hammer
Study Chair: John Mellors
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000912     History of Changes
Other Study ID Numbers: ACTG 398, 11354, Substudy ACTG 5003s
Study First Received: November 2, 1999
Last Updated: July 26, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Placebos
Drug Therapy, Combination
HIV Protease Inhibitors
VX 478
Anti-HIV Agents
Viral Load
efavirenz

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
Carnitine
Protease Inhibitors
Indinavir
Saquinavir
Nelfinavir
Amprenavir
HIV Protease Inhibitors
Adefovir
Adefovir dipivoxil
Efavirenz
Abacavir
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 18, 2014