A Randomized, Prospective Study of the Efficacy, Safety and Tolerability of Two Doses of GW433908Ritonavir Given With Abacavir/Lamivudine Fixed Dose Combination

NCT00335270 | Completed Phase 4

• 1 other identifier: 6692-05-12R1
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the antiretroviral efficacy, safety, and tolerability of fos-amprenavir boosted with either of two doses of ritonavir (RTV) when administered in combination with ABC/3TC (abacavir/lamivudine, Epzicom®) FDC (fixed dose combination) in a once-daily regimen over 96 weeks in ART-naïve, HIV-infected adults

Conditions

HIV

Keywords

HIV Type 1

Outcome Measures

Primary Outcomes (2)

• Proportion of subjects with plasma HIV 1 RNA <400 copies at week 48

• Proportion of subjects who experience drug related discontinuations at Week 48

Secondary Outcomes (11)

• Proportion of subjects who achieve plasma HIV 1 RNA<400 copies/mL at Weeks 24 and 96

• Proportion of subjects who achieve plasma HIV-1 RNA <50 copies/mL at Weeks 24, 48, and 96.

• Absolute values and change from baseline in plasma HIV-1 RNA and CD4+ cell counts at Weeks 24, 48, and 96.

• Development and identification of genotypic resistance mutations and phenotypic resistance at virologic failure.

• Incidence of Grades 2 to 4 AEs, treatment-limiting AEs, and serious adverse events (SAEs) over 24, 48, and 96 weeks.

Interventions

fos-amprenavir calcium, ritonavir DRUG

abacavir/lamivudine as Epzicom DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1 infection
• Male or Female 18 years of age or older
• Has plasma HIV-1 RNA (viral load) 1,000 or more copies/mL at screening
• Subject is antiretroviral-naïve ( less than 7 days of prior therapy with any agent
• Competency
• Not pregnant and willing to use effective birth control if applicable.

You may not qualify if:

• Inability to comply due to pre-existing mental, physical, or substance abuse disorder or other reason.
• Has active/acute CDC Clinical Category C event at screening.
• Has history of inflammatory bowel disease, gastrointestinal malignancy, intestinal ischemia, malabsorption or other gastrointestinal dysfunction.
• Females who are pregnant or breastfeeding.
• Has a serious medical condition, such as diabetes, congestive heart failure, cardiomyopathy or other cardiac dysfunction, which in the opinion of the investigator would compromise the safety of the subject.
• Has ongoing clinically relevant pancreatitis or clinically relevant hepatitis at screening.
• Requires treatment with foscarnet, hydroxyurea or other agents with documented activity against HIV-1 in vitro within 28 days of study drug administration.
• Has an acute laboratory abnormality at screening that, in the opinion of the investigator, should preclude the subject's participation in the study. Any Grade 4 laboratory result would exclude a subject from study participation.
• Has required treatment with radiation therapy or cytotoxic chemotherapeutic agents within 28 days prior to screening, or has an anticipated need for such a treatment within the study period.
• Requires treatment with immunomodulating agents (such as systemic corticosteroids, interleukins, vaccines, or interferons) within 28 days prior to screening or subject has received an HIV-1 immunotherapeutic vaccine within 90 days prior to screening.
• Has a history of allergy to any of the study drugs or any excipients therein.
• Is enrolled or plans to enroll in one or more investigational drug protocols, which may impact HIV RNA suppression.
• Requiring treatment with pharmacological agents for diabetes, or elevated triglycerides/cholesterol.
• Has an AST or ALT \>5 times the upper limit of normal (ULN).
• Has an estimated creatinine clearance \<50 mL/min via the Cockcroft-Gault method

Sponsors & Collaborators

• Duke University: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

University of Miami School of Medicine

Miami, Florida, 33136, United States

Location

Related Publications (10)

• Behrens G, Dejam A, Schmidt H, Balks HJ, Brabant G, Korner T, Stoll M, Schmidt RE. Impaired glucose tolerance, beta cell function and lipid metabolism in HIV patients under treatment with protease inhibitors. AIDS. 1999 Jul 9;13(10):F63-70. doi: 10.1097/00002030-199907090-00001.

  PMID: 10416516 BACKGROUND

• Carpenter CC, Cooper DA, Fischl MA, Gatell JM, Gazzard BG, Hammer SM, Hirsch MS, Jacobsen DM, Katzenstein DA, Montaner JS, Richman DD, Saag MS, Schechter M, Schooley RT, Thompson MA, Vella S, Yeni PG, Volberding PA. Antiretroviral therapy in adults: updated recommendations of the International AIDS Society-USA Panel. JAMA. 2000 Jan 19;283(3):381-90. doi: 10.1001/jama.283.3.381.

  PMID: 10647802 BACKGROUND

• Dube MP, Sprecher D, Henry WK, Aberg JA, Torriani FJ, Hodis HN, Schouten J, Levin J, Myers G, Zackin R, Nevin T, Currier JS; Adult AIDS Clinical Trial Group Cardiovascular Disease Focus Group. Preliminary guidelines for the evaluation and management of dyslipidemia in adults infected with human immunodeficiency virus and receiving antiretroviral therapy: Recommendations of the Adult AIDS Clinical Trial Group Cardiovascular Disease Focus Group. Clin Infect Dis. 2000 Nov;31(5):1216-24. doi: 10.1086/317429. Epub 2000 Nov 7.

  PMID: 11073755 BACKGROUND

• Fung HB, Kirschenbaum HL, Hameed R. Amprenavir: a new human immunodeficiency virus type 1 protease inhibitor. Clin Ther. 2000 May;22(5):549-72. doi: 10.1016/S0149-2918(00)80044-2.

  PMID: 10868554 BACKGROUND

• McComsey GA, Ward DJ, Hessenthaler SM, Sension MG, Shalit P, Lonergan JT, Fisher RL, Williams VC, Hernandez JE; Trial to Assess the Regression of Hyperlactatemia and to Evaluate the Regression of Established Lipodystrophy in HIV-1-Positive Subjects (TARHEEL; ESS40010) Study Team. Improvement in lipoatrophy associated with highly active antiretroviral therapy in human immunodeficiency virus-infected patients switched from stavudine to abacavir or zidovudine: the results of the TARHEEL study. Clin Infect Dis. 2004 Jan 15;38(2):263-70. doi: 10.1086/380790. Epub 2003 Dec 18.

  PMID: 14699460 BACKGROUND

• Moore KH, Barrett JE, Shaw S, Pakes GE, Churchus R, Kapoor A, Lloyd J, Barry MG, Back D. The pharmacokinetics of lamivudine phosphorylation in peripheral blood mononuclear cells from patients infected with HIV-1. AIDS. 1999 Nov 12;13(16):2239-50. doi: 10.1097/00002030-199911120-00006.

  PMID: 10563709 BACKGROUND

• Noble S, Goa KL. Amprenavir: a review of its clinical potential in patients with HIV infection. Drugs. 2000 Dec;60(6):1383-410. doi: 10.2165/00003495-200060060-00012.

  PMID: 11152018 BACKGROUND

• 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.

  PMID: 14707788 BACKGROUND

• Tsiodras S, Mantzoros C, Hammer S, Samore M. Effects of protease inhibitors on hyperglycemia, hyperlipidemia, and lipodystrophy: a 5-year cohort study. Arch Intern Med. 2000 Jul 10;160(13):2050-6. doi: 10.1001/archinte.160.13.2050.

  PMID: 10888979 BACKGROUND

• Walli R, Herfort O, Michl GM, Demant T, Jager H, Dieterle C, Bogner JR, Landgraf R, Goebel FD. Treatment with protease inhibitors associated with peripheral insulin resistance and impaired oral glucose tolerance in HIV-1-infected patients. AIDS. 1998 Oct 22;12(15):F167-73. doi: 10.1097/00002030-199815000-00001.

  PMID: 9814858 BACKGROUND

MeSH Terms

Interventions

Ritonavir; abacavir; Lamivudine; abacavir, lamivudine drug combination

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Study Officials

• Charles Hicks, MD

  Duke University

  PRINCIPAL INVESTIGATOR

• Rafael E Campo, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

• Jason Flamm, MD

  Medicine 4

  PRINCIPAL INVESTIGATOR

• Jeffrey Lennox, MD

  Emory University

  PRINCIPAL INVESTIGATOR

• Rodger MacArthur, MD

  Wayne State University

  PRINCIPAL INVESTIGATOR

• Jeffrey P Nadler, MD

  Hillsborough County Health Department

  PRINCIPAL INVESTIGATOR

• John H. Schrank, MD

  Greenville Hospital System

  PRINCIPAL INVESTIGATOR

• Louis Sloan, MD

  North Texas Infectious Disease Consultants

  PRINCIPAL INVESTIGATOR

• Jeffrey Stephens, MD

  Mercer University School of Medicine

  PRINCIPAL INVESTIGATOR

• David A Wohl, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2006
• First Posted: June 9, 2006
• Study Start: March 1, 2006
• Primary Completion: December 1, 2007
• Study Completion: December 1, 2007
• Last Updated: May 14, 2013

Record last verified: 2013-05

Locations

US (1)