"The Once A Day Protease Inhibitor Regimens"

NCT ID: NCT00242216

Last Updated: 2014-01-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 76 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-05-31
• Study Completion Date: 2010-03-31

Brief Summary

Atazanavir (ATV) and fosamprenavir (fAPV) are new protease inhibitors that can be administered once-a-day and boosted with ritonavir (r). Prior studies have demonstrated that both are effective in treatment of ARV-naïve HIV-infected people. This study was designed to demonstrate if a HAART regimen containing ATV/r is not inferior to a HAART regimen containing fAPV/r, in ARV-naïve patients over a 96-week period.

This is a phase IV, single center, randomized, open label, 2-arm clinical trial in ARV therapy-naïve patients with HIV-1 RNA >1,000 copes/mL and CD4 cell count <350 cells/mm3. Patients will be randomized to receive tenofovir and emtricitabine plus either ATV (300mg qd) and ritonavir (100mg qd) or fAPV (1400mg qd) and ritonavir (200mg qd).

Detailed Description

Over the past decade, there have been significant advances toward fighting the progression of HIV disease. Current treatment strategies consist of utilization of potent combination antiretroviral therapy to suppress HIV replication below detectable limits limiting the potential for the emergence of resistant viruses, boosting CD4 cell counts and thereby delaying disease progression. Treatment of HIV-1 infection with Highly Active Antiretroviral Therapy (HAART) regimens containing a protease inhibitor (PI) and two nucleoside reverse transcriptase inhibitor (NRTIs) has been shown to prolong survival and decrease disease progression. Despite these potent antiretroviral agents, current available therapies continue to fail in some patients. Poor adherence to complex treatment regimens remains a significant cause of suboptimal viral suppression leading to emerge of resistant virus. Atazanavir and fosamprenavir were recently FDA approved protease inhibitors. The efficacy and safety profile of these two drugs have been established in clinical trials enrolling antiretroviral therapy naïve and protease inhibitor experienced patients. Atazanavir and fosamprenavir are the only protease inhibitors approved for a once a day regimen and this may set a new standard for treatment of antiretroviral therapy naïve HIV infected patients. Adherence to the medicines, a key component of treatment success, could be significantly improved by using these once daily regimens. However, no head-to-head trials comparing the safety and efficacy of fosamprenavir and atazanavir have been published. This prospective, randomized, open label 2-arm study will compare these two protease inhibitors for therapy of antiretroviral treatment-naïve HIV-infected patients. Patients who are successfully screened for eligibility will be randomized to receive tenofovir and emtricitabine plus either atazanavir (300mg qd) and ritonavir (100mg qd) or fosamprenavir (1400mg qd) and ritonavir (200mg qd). Participants will undergo assessment on day 1 and attend study visits at weeks 6, 12 and every 3 months until the completion of the study on week 96. "Antiretroviral Medication Self-Report" and "3-Day HIV Medication Self-Report" questionnaires will be applied at weeks 6, 12 and every 3 month, thereafter, until week 96. "Changes in Body Appearance" questionnaire will be applied at baseline and weeks 24, 48, 72, and 96.

Conditions

HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Atazanavir oral once daily

HIV treatment

Group Type: ACTIVE_COMPARATOR

ritonavir-boosted atazanavir

Intervention Type: DRUG

100 mg ritonavir plus 300 mg atazanavir in combination with tenofovir-emtricitabine fixed dose combination given once daily.

Fosamprenavir oral once daily

HIV treatment

Group Type: ACTIVE_COMPARATOR

ritonavir-boosted fosamprenavir

Intervention Type: DRUG

100 mg ritonavir plus 1,400 mg fosamprenavir in combination with tenofovir-emtricitabine fixed dose combination given once daily.

Interventions

ritonavir-boosted atazanavir

100 mg ritonavir plus 300 mg atazanavir in combination with tenofovir-emtricitabine fixed dose combination given once daily.

Intervention Type: DRUG

ritonavir-boosted fosamprenavir

100 mg ritonavir plus 1,400 mg fosamprenavir in combination with tenofovir-emtricitabine fixed dose combination given once daily.

Intervention Type: DRUG

Other Intervention Names

Reyataz plus Norvir; Lexiva plus Norvir

Eligibility Criteria

Inclusion Criteria

• 18 years of age or older.
• Patient agrees to participate in the study by giving written informed consent.
• Documentation of HIV infection.
• No prior treatment with any anti-retroviral agent.
• CD4 cell count < 350 cells x mm3 or with an AIDS defining condition.
• Viral load > 1,000 copies/mL

Exclusion Criteria

• Less than 18 years old.
• Current pregnancy or breastfeeding.
• Any previous antiretroviral regimen.
• Severe hepatic impairment that precludes the use of either study drug. This will be defined as any laboratory value of Grade 3 or 4 on the ACTG scale.
• Use of any contra-indicated medication as defined in the package insert for each drug.
• Any condition that, in the judgment of the investigator, precludes successful participation in the study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role: lead

Responsible Party

Roberto Arduino

Professor - Internal Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Roberto C Arduino, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center, Houston

Locations

Thomas Street Health Center

Houston, Texas, United States

Countries

United States

References

Murphy RL, Sanne I, Cahn P, Phanuphak P, Percival L, Kelleher T, Giordano M. Dose-ranging, randomized, clinical trial of atazanavir with lamivudine and stavudine in antiretroviral-naive subjects: 48-week results. AIDS. 2003 Dec 5;17(18):2603-14. doi: 10.1097/00002030-200312050-00007.

Reference Type: BACKGROUND

PMID: 14685054 (View on PubMed)

Sax PE. Meeting notes from the 2nd International AIDS Society Conference on HIV Pathogenesis and Treatment. Atazanavir in treatment-experienced patients. AIDS Clin Care. 2003 Sep;15(9):78.

Reference Type: BACKGROUND

PMID: 14666914 (View on PubMed)

Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2003 Jul-Aug;25(6):483-506.

Reference Type: BACKGROUND

PMID: 12949633 (View on PubMed)

Goldsmith DR, Perry CM. Atazanavir. Drugs. 2003;63(16):1679-93; discussion 1694-5. doi: 10.2165/00003495-200363160-00003.

Reference Type: BACKGROUND

PMID: 12904086 (View on PubMed)

Rodriguez-French A, Boghossian J, Gray GE, Nadler JP, Quinones AR, Sepulveda GE, Millard JM, Wannamaker PG. The NEAT study: a 48-week open-label study to compare the antiviral efficacy and safety of GW433908 versus nelfinavir in antiretroviral therapy-naive HIV-1-infected patients. J Acquir Immune Defic Syndr. 2004 Jan 1;35(1):22-32. doi: 10.1097/00126334-200401010-00003.

Reference Type: BACKGROUND

PMID: 14707788 (View on PubMed)

SOLO trial results released. AIDS Patient Care STDS. 2003 Feb;17(2):95. doi: 10.1089/108729103321150827. No abstract available.

Reference Type: BACKGROUND

PMID: 12639292 (View on PubMed)

Falcoz C, Jenkins JM, Bye C, Hardman TC, Kenney KB, Studenberg S, Fuder H, Prince WT. Pharmacokinetics of GW433908, a prodrug of amprenavir, in healthy male volunteers. J Clin Pharmacol. 2002 Aug;42(8):887-98. doi: 10.1177/009127002401102803.

Reference Type: BACKGROUND

PMID: 12162471 (View on PubMed)

Vierling P, Greiner J. Prodrugs of HIV protease inhibitors. Curr Pharm Des. 2003;9(22):1755-70. doi: 10.2174/1381612033454441.

Reference Type: BACKGROUND

PMID: 12871195 (View on PubMed)

Mannheimer SB, Matts J, Telzak E, Chesney M, Child C, Wu AW, Friedland G; Terry Beirn Community Programs for Clinical Research on AIDS. Quality of life in HIV-infected individuals receiving antiretroviral therapy is related to adherence. AIDS Care. 2005 Jan;17(1):10-22. doi: 10.1080/09540120412331305098.

Reference Type: BACKGROUND

PMID: 15832830 (View on PubMed)

Holmes A, Lucke J, Maghidman S, Fernandez-Bussy S, Barnett B, Arduino R. Tenofovir associated nephrotoxicity is dose-dependent ritonavir administration a co-factor? XVI International AIDS Conference. Toronto, Canada. August 13-18, 2006. Abstract TUPE0085.

Reference Type: RESULT

Bell TK, Holmes A, McCormack OE, Barnett BJ, Arduino RC. Changing Genotypic Resistance Patterns and Demographics of Antiretroviral-Naïve HIV Patients in Houston: 1999-2006. 44th Annual Meeting of the Infectious Diseases Society of America (IDSA). Toronto, Canada. October 12-15, 2006. Abstract 975.

Reference Type: RESULT

Holmes A, Bell T, Barnett B, Arduino R. Emerging resistance mutations in once-daily ritonavir-boosted protease inhibitor-containing antiretroviral regimens. 44th Annual Meeting of the Infectious Diseases Society of America (IDSA). Toronto, Canada. October 12-15, 2006. Abstract 973.

Reference Type: RESULT

Other Identifiers

HSC-MS-03-315

Identifier Type: -

Identifier Source: org_study_id