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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000912
• Other study ID #: ACTG 398
• Secondary ID: 11354Substudy AC
• Status: Completed
• Phase: Phase 2
• Est. completion date: May 2000

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.]

Recruitment information / eligibility

• Status: Completed
• Enrollment: 475
• Est. completion date: May 2000
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Indinavir sulfate

• Abacavir sulfate

• Amprenavir

• Nelfinavir mesylate

• Efavirenz

• Levocarnitine

• Adefovir dipivoxil

• Saquinavir

Locations

Country	Name	City	State
Puerto Rico	Univ of Puerto Rico	San Juan
United States	Emory Hemo Comp Evaluation Clinic / East TN Comp Hemo Ctr	Atlanta	Georgia
United States	Emory Univ	Atlanta	Georgia
United States	Johns Hopkins Hosp	Baltimore	Maryland
United States	Boston Med Ctr	Boston	Massachusetts
United States	Harvard (Massachusetts Gen Hosp)	Boston	Massachusetts
United States	SUNY / Erie County Med Ctr at Buffalo	Buffalo	New York
United States	Cook County Hosp	Chicago	Illinois
United States	Northwestern Univ Med School	Chicago	Illinois
United States	Rush Presbyterian - Saint Luke's Med Ctr	Chicago	Illinois
United States	Univ of Cincinnati	Cincinnati	Ohio
United States	Ohio State Univ Hosp Clinic	Columbus	Ohio
United States	Univ of Colorado Health Sciences Ctr	Denver	Colorado
United States	Duke Univ Med Ctr	Durham	North Carolina
United States	Univ of Texas Galveston	Galveston	Texas
United States	Moses H Cone Memorial Hosp	Greensboro	North Carolina
United States	Milton S Hershey Med Ctr	Hershey	Pennsylvania
United States	Queens Med Ctr	Honolulu	Hawaii
United States	Univ of Hawaii	Honolulu	Hawaii
United States	UCLA CARE Ctr	Los Angeles	California
United States	Univ of Southern California / LA County USC Med Ctr	Los Angeles	California
United States	USC Univ Hosp & Ambulatory Hlth Care Ctr / USC Med Ctr	Los Angeles	California
United States	Willow Clinic	Menlo Park	California
United States	Univ of Miami School of Medicine	Miami	Florida
United States	Univ of Minnesota	Minneapolis	Minnesota
United States	Charity Hosp / Tulane Univ Med School	New Orleans	Louisiana
United States	Tulane Univ School of Medicine	New Orleans	Louisiana
United States	Bellevue Hosp / New York Univ Med Ctr	New York	New York
United States	Chelsea Ctr	New York	New York
United States	Cornell Univ Med Ctr	New York	New York
United States	Mem Sloan - Kettering Cancer Ctr	New York	New York
United States	Mount Sinai Med Ctr	New York	New York
United States	Univ of Pennsylvania at Philadelphia	Philadelphia	Pennsylvania
United States	Univ of Pittsburgh Med Ctr	Pittsburgh	Pennsylvania
United States	Univ of Rochester Medical Center	Rochester	New York
United States	St Louis Regional Hosp / St Louis Regional Med Ctr	Saint Louis	Missouri
United States	Univ of California / San Diego Treatment Ctr	San Diego	California
United States	San Francisco AIDS Clinic / San Francisco Gen Hosp	San Francisco	California
United States	San Francisco Gen Hosp	San Francisco	California
United States	Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium	San Jose	California
United States	Univ of Washington	Seattle	Washington
United States	San Mateo AIDS Program / Stanford Univ	Stanford	California
United States	Stanford Univ Med Ctr	Stanford	California
United States	Tripler Army Med Ctr	Tripler AMC	Hawaii
United States	Howard Univ	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (5)

Ghosh P, Ghosh K, Tiwari RC. Joint modeling of longitudinal data and informative dropout time in the presence of multiple changepoints. Stat Med. 2011 Mar 15;30(6):611-26. doi: 10.1002/sim.4119. Epub 2010 Nov 30. — View Citation

Hammer SM, Vaida F, Bennett KK, Holohan MK, Sheiner L, Eron JJ, Wheat LJ, Mitsuyasu RT, Gulick RM, Valentine FT, Aberg JA, Rogers MD, Karol CN, Saah AJ, Lewis RH, Bessen LJ, Brosgart C, DeGruttola V, Mellors JW; AIDS Clinical Trials Group 398 Study Team. Dual vs single protease inhibitor therapy following antiretroviral treatment failure: a randomized trial. JAMA. 2002 Jul 10;288(2):169-80. — View Citation

Pfister M, Labbé L, Hammer SM, Mellors J, Bennett KK, Rosenkranz S, Sheiner LB; Adult AIDS Clinical Trial Group Study 398. Population pharmacokinetics and pharmacodynamics of efavirenz, nelfinavir, and indinavir: Adult AIDS Clinical Trial Group Study 398. Antimicrob Agents Chemother. 2003 Jan;47(1):130-7. — View Citation

Pfister M, Labbé L, Lu JF, Hammer SM, Mellors J, Bennett KK, Rosenkranz S, Sheiner LB; AIDS Clinical Trial Group Protocol 398 Investigators. Effect of coadministration of nelfinavir, indinavir, and saquinavir on the pharmacokinetics of amprenavir. Clin Pharmacol Ther. 2002 Aug;72(2):133-41. — View Citation

Sun J, Nagaraj HN, Reynolds NR. Discrete stochastic models for compliance analysis based on an AIDS Clinical Trial Group (ACTG) study. Biom J. 2007 Aug;49(5):731-41. — View Citation