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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00000912

Collaborator

(none)

475

Enrollment

Locations

10.6

Patients Per Site

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	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

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.]

Study Design

Study Type:

Interventional

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

Actual Study Completion Date :

May 1, 2000

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Univ of Southern California / LA County USC Med Ctr	Los Angeles	California	United States	900331079
2	USC Univ Hosp & Ambulatory Hlth Care Ctr / USC Med Ctr	Los Angeles	California	United States	900334508
3	UCLA CARE Ctr	Los Angeles	California	United States	90095
4	Willow Clinic	Menlo Park	California	United States	94025
5	Univ of California / San Diego Treatment Ctr	San Diego	California	United States	921036325
6	San Francisco AIDS Clinic / San Francisco Gen Hosp	San Francisco	California	United States	941102859
7	San Francisco Gen Hosp	San Francisco	California	United States	941102859
8	Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium	San Jose	California	United States	951282699
9	San Mateo AIDS Program / Stanford Univ	Stanford	California	United States	943055107
10	Stanford Univ Med Ctr	Stanford	California	United States	943055107
11	Univ of Colorado Health Sciences Ctr	Denver	Colorado	United States	80262
12	Howard Univ	Washington	District of Columbia	United States	20059
13	Univ of Miami School of Medicine	Miami	Florida	United States	331361013
14	Emory Univ	Atlanta	Georgia	United States	30308
15	Emory Hemo Comp Evaluation Clinic / East TN Comp Hemo Ctr	Atlanta	Georgia	United States	303652225
16	Queens Med Ctr	Honolulu	Hawaii	United States	96816
17	Univ of Hawaii	Honolulu	Hawaii	United States	96816
18	Tripler Army Med Ctr	Tripler AMC	Hawaii	United States	96859
19	Northwestern Univ Med School	Chicago	Illinois	United States	60611
20	Cook County Hosp	Chicago	Illinois	United States	60612
21	Rush Presbyterian - Saint Luke's Med Ctr	Chicago	Illinois	United States	60612
22	Charity Hosp / Tulane Univ Med School	New Orleans	Louisiana	United States	70112
23	Tulane Univ School of Medicine	New Orleans	Louisiana	United States	70112
24	Johns Hopkins Hosp	Baltimore	Maryland	United States	21287
25	Harvard (Massachusetts Gen Hosp)	Boston	Massachusetts	United States	02114
26	Boston Med Ctr	Boston	Massachusetts	United States	02118
27	Univ of Minnesota	Minneapolis	Minnesota	United States	55455
28	St Louis Regional Hosp / St Louis Regional Med Ctr	Saint Louis	Missouri	United States	63112
29	SUNY / Erie County Med Ctr at Buffalo	Buffalo	New York	United States	14215
30	Bellevue Hosp / New York Univ Med Ctr	New York	New York	United States	10016
31	Chelsea Ctr	New York	New York	United States	10021
32	Cornell Univ Med Ctr	New York	New York	United States	10021
33	Mem Sloan - Kettering Cancer Ctr	New York	New York	United States	10021
34	Mount Sinai Med Ctr	New York	New York	United States	10029
35	Univ of Rochester Medical Center	Rochester	New York	United States	14642
36	Duke Univ Med Ctr	Durham	North Carolina	United States	27710
37	Moses H Cone Memorial Hosp	Greensboro	North Carolina	United States	27401
38	Univ of Cincinnati	Cincinnati	Ohio	United States	452670405
39	Ohio State Univ Hosp Clinic	Columbus	Ohio	United States	432101228
40	Milton S Hershey Med Ctr	Hershey	Pennsylvania	United States	170330850
41	Univ of Pennsylvania at Philadelphia	Philadelphia	Pennsylvania	United States	19104
42	Univ of Pittsburgh Med Ctr	Pittsburgh	Pennsylvania	United States	15213
43	Univ of Texas Galveston	Galveston	Texas	United States	775550435
44	Univ of Washington	Seattle	Washington	United States	981224304
45	Univ of Puerto Rico	San Juan		Puerto Rico	009365067