KIVEXA Vs TRUVADA, Both Administered With Efavirenz, In ART-Naive Subjects

NCT00549198 | Completed Phase 4 Results

• 1 other identifier: CNA109586
• Study Type: interventional
• Target: 392
• Locations: 13 countries
• Sites: 68

Brief Summary

Recently, the fixed-dose combinations (FDC) KIVEXA™ (abacavir/lamivudine) and TRUVADA (tenofovir disoproxil fumarate/emtricitabine) have facilitated the usage of once-daily regimens. However data from head-to-head randomized trials comparing these two FDCs as part of an initial regimen are not available at present. The long-term toxicity profiles of these regimens are of particular importance, as treatment of HIV is currently life-long and therefore, minimizing long-term toxicity and maximizing adherence and duration of regimen maintenance are critical therapy objectives. The primary endpoint is estimated glomerular filtration rate (GFR), as measured by the modified diet in renal disease (MDRD) equation, a validated estimate of renal function.

Conditions

Infection, Human Immunodeficiency Virus I; HIV Infection

Keywords

tenofovir; HIV; efavirenz; naive; lamivudine; abacavir; emtricitabine; renal

Outcome Measures

Primary Outcomes (1)

• Mean Change From Baseline in Estimated Glomerular Filtration Rate (GFR), Calculated by Modification of Diet in Renal Disease (MDRD) Equation, at Week 48

  Change from baseline was calculated as the Week 48 value minus the baseline value. GFR is a measure of the rate at which blood is filtered by the kidney. MDRD is an equation (calculation) used to estimate GFR in participants with impaired renal function based on serum creatinine, age, race, and gender. GFR (mL/min/1.73 m\^2) = 175 \* (Scr)\^-1.154 \* (Age)\^-0.203 \* (0.742 if female) \* (1.212 if African American) (conventional units). mL, milliliters; min, minute; m\^2, meters squared; Scr, serum creatinine; BMI, body mass index.

  Baseline, Week 48

Secondary Outcomes (49)

• Mean Change From Baseline in Estimated Glomerular Filtration Rate (GFR), Calculated by Modification of Diet in Renal Disease (MDRD) Equation, at Week 24

  Baseline, Week 24

• Mean Change From Baseline in Estimated Glomerular Filtration Rate (GFR), Calculated by Modification of Diet in Renal Disease (MDRD) Equation, at Week 96

  Baseline, Week 96

• Mean Change From Baseline in Estimated GFR, Calculated by Cockcroft-Gault Equation, at Week 24

  Baseline, Week 24

• Mean Change From Baseline in Estimated GFR, Calculated by Cockcroft-Gault Equation, at Week 48

  Baseline, Week 48

• Mean Change From Baseline in Estimated GFR, Calculated by Cockcroft-Gault Equation, at Week 96

  Baseline, Week 96

Other Outcomes (8)

• Exploratory Analysis of Change From Baseline in Albumin as a Ratio to Urine Creatinine at Week 96

  Baseline, Week 96

• Exploratory Analysis of Change From Baseline in Beta 2 Microglobulin (B2M) as a Ratio to Urine Creatinine at Week 96

  Baseline, Week 96

• Exploratory Analysis of Change From Baseline in N-acetyl-B-glucosaminidase (NAG) as a Ratio to Urine Creatinine at Week 96

  Baseline, Week 96

Study Arms (2)

ABC/3TC + EFV

EXPERIMENTAL

Drug: Abacavir/lamivudine and efavirenz

TDF/FTC + EFV

ACTIVE COMPARATOR

Drug: Tenofovir/Emtricitabine and efavirenz

Interventions

Abacavir/lamivudine and efavirenz DRUG

ABC/3TC + EFV

Tenofovir/Emtricitabine and efavirenz DRUG

TDF/FTC + EFV

Eligibility Criteria

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

You may qualify if:

• Subject is at least 18 years of age.
• Subject is antiretroviral-naïve (defined as having no previous therapy with any NNRTI and 14 days of prior therapy with any other antiretroviral).
• Subject has plasma HIV-1 RNA 1,000 copies/mL at screening. This test may be repeated once within the 45-day screening window.
• Subject is willing and able to understand and provide written informed consent prior to participation in this study.
• A female is eligible to enter and participate in the study if she is of:
• Non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal); or,
• Child-bearing potential, has a negative pregnancy test at screen and agrees to one of the following methods of contraception (any contraception method must be used consistently and correctly, i.e., in accordance with both the approved product label and the instructions of a physician):
• Sterilization (female subject or male partner of female subject).
• Prior to randomization, subjects must have been screened and be negative for the HLA-B\*5701 allele. Test may be performed by local laboratory and results must be available for source document verification according to local practices.

You may not qualify if:

• Subject is in the initial acute phase of a CDC Clinical Category C infection at Baseline.
• Subject is enrolled in one or more investigational drug protocols, which may impact HIV RNA suppression.
• Subject is, in the opinion of the Investigator, unable to complete the study dosing period and protocol evaluations and assessments.
• Subject is either pregnant or breastfeeding.
• Subject suffers from a serious medical condition, which in the opinion of the Investigator would compromise the safety of the subject.
• Subject has a history of inflammatory bowel disease or other gastrointestinal dysfunction.
• Subject has any acute laboratory abnormality at screening.
• Subject has an estimated creatinine clearance within the screening period \<50mL/min via the Cockcroft-Gault method.
• Alanine aminotransferase (ALT) \>5 times the upper limit of normal.
• Subjects with a history of thyroid disease, hyperparathyroid disease, chronic hyper or hypocalcemia, vitamin D deficiency, or receiving thyroid hormone or parathyroid hormone replacement within 28 days prior to screening.
• Subjects with a history of systemic inflammatory arthritis.
• Subjects who are hepatitis B positive at screening.
• Subject requires treatment with radiation therapy or cytotoxic chemotherapeutic agents.
• Subject has received treatment with an HIV-1 immunotherapeutic vaccine or any agents with documented activity against HIV-1 in vitro within 28 days prior to Screening, or an anticipated need during the study.
• Subjects who require treatment with any of the following medications within 28 days of commencement of investigational product, or an anticipated need during the study:

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (68)

GSK Investigational Site

Innsbruck, A-6020, Austria

Location

GSK Investigational Site

Salzburg, A-5020, Austria

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GSK Investigational Site

Vienna, A-1090, Austria

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GSK Investigational Site

Vienna, A-1140, Austria

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GSK Investigational Site

Bruges, 8000, Belgium

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GSK Investigational Site

Brussels, 1000, Belgium

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GSK Investigational Site

Charleroi, 6000, Belgium

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GSK Investigational Site

Ghent, 9000, Belgium

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GSK Investigational Site

Leuven, 3000, Belgium

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GSK Investigational Site

Aalborg, DK-9000, Denmark

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GSK Investigational Site

Aarhus N, 8200, Denmark

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GSK Investigational Site

Copenhagen, DK-2100, Denmark

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GSK Investigational Site

Hvidovre, DK-2650, Denmark

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GSK Investigational Site

Odense C, 5000, Denmark

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GSK Investigational Site

Garches, 92380, France

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GSK Investigational Site

Levallois-Perret, 92300, France

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GSK Investigational Site

Saint-Denis, 93205, France

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GSK Investigational Site

Heidelberg, Baden-Wurttemberg, 69115, Germany

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GSK Investigational Site

Munich, Bavaria, 80335, Germany

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GSK Investigational Site

Hamburg, Hamburg, 20146, Germany

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GSK Investigational Site

Hamburg, Hamburg, 20246, Germany

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GSK Investigational Site

Hanover, Lower Saxony, 30159, Germany

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GSK Investigational Site

Hanover, Lower Saxony, 30625, Germany

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GSK Investigational Site

Düsseldorf, North Rhine-Westphalia, 40237, Germany

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GSK Investigational Site

Essen, North Rhine-Westphalia, 45122, Germany

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GSK Investigational Site

Leipzig, Saxony, 04170, Germany

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GSK Investigational Site

Berlin, State of Berlin, 13353, Germany

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GSK Investigational Site

Dublin, 7, Ireland

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GSK Investigational Site

Dublin, 8, Ireland

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GSK Investigational Site

Ferrara, Emilia-Romagna, 44100, Italy

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GSK Investigational Site

Modena, Emilia-Romagna, 41100, Italy

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GSK Investigational Site

Rimini, Emilia-Romagna, 47900, Italy

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GSK Investigational Site

Rome, Lazio, 00149, Italy

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GSK Investigational Site

Legnano (MI, Lombardy, 20025, Italy

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GSK Investigational Site

Milan, Lombardy, 20127, Italy

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GSK Investigational Site

Milan, Lombardy, 20142, Italy

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GSK Investigational Site

Turin, Piedmont, 10149, Italy

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GSK Investigational Site

Riga, LV 1006, Latvia

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GSK Investigational Site

Alkmaar, 1815 JD, Netherlands

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GSK Investigational Site

Groningen, 9713 GZ, Netherlands

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GSK Investigational Site

Rotterdam, 3078 HT, Netherlands

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GSK Investigational Site

The Hague, 2512 VA, Netherlands

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GSK Investigational Site

Utrecht, 3584 CX, Netherlands

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GSK Investigational Site

Amadora, 2720-276, Portugal

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GSK Investigational Site

Madrid, 28034, Spain

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GSK Investigational Site

Valencia, 46015, Spain

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GSK Investigational Site

Basel, 4031, Switzerland

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GSK Investigational Site

Bern, 3010, Switzerland

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GSK Investigational Site

Lausanne, 1011, Switzerland

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GSK Investigational Site

Sankt Gallen, 9007, Switzerland

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GSK Investigational Site

Zurich, 8038, Switzerland

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GSK Investigational Site

Zurich, 8091, Switzerland

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GSK Investigational Site

Manchester, Lancashire, M8 5RB, United Kingdom

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GSK Investigational Site

Woolwich, London, London, SE18 4QH, United Kingdom

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GSK Investigational Site

Edinburgh, Midlothian, EH4 2XU, United Kingdom

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GSK Investigational Site

Brighton, Sussex East, BN2 1ES, United Kingdom

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GSK Investigational Site

Birmingham, B4 6DH, United Kingdom

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GSK Investigational Site

Birmingham, WS2 9PS, United Kingdom

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GSK Investigational Site

Farnworth, Bolton, BL4 0JR, United Kingdom

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GSK Investigational Site

Gloucester, GL1 3NN, United Kingdom

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GSK Investigational Site

Leicester, LE1 5WW, United Kingdom

Location

GSK Investigational Site

London, E1 1BB, United Kingdom

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GSK Investigational Site

London, N18 1QX, United Kingdom

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GSK Investigational Site

London, NW3 2QG, United Kingdom

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GSK Investigational Site

London, SW10 9TH, United Kingdom

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GSK Investigational Site

London, SW17 0QT, United Kingdom

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GSK Investigational Site

Middlesbrough, TS4 3BW, United Kingdom

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GSK Investigational Site

Sheffield, S10 2JF, United Kingdom

Location

Related Publications (1)

• Post FA, Moyle GJ, Stellbrink HJ, Domingo P, Podzamczer D, Fisher M, Norden AG, Cavassini M, Rieger A, Khuong-Josses MA, Branco T, Pearce HC, Givens N, Vavro C, Lim ML. Randomized comparison of renal effects, efficacy, and safety with once-daily abacavir/lamivudine versus tenofovir/emtricitabine, administered with efavirenz, in antiretroviral-naive, HIV-1-infected adults: 48-week results from the ASSERT study. J Acquir Immune Defic Syndr. 2010 Sep;55(1):49-57. doi: 10.1097/QAI.0b013e3181dd911e.

  PMID: 20431394 BACKGROUND

MeSH Terms

Conditions

Infections; HIV Infections

Interventions

abacavir; Lamivudine; efavirenz; Tenofovir; Emtricitabine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: October 24, 2007
• First Posted: October 25, 2007
• Study Start: June 1, 2007
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: April 12, 2011
• Results First Posted: October 15, 2010

Record last verified: 2011-04

Locations

DE (10); CH (6); IE (2); LA (1); GB (16); NL (5); IT (8); FR (3); DK (5); PT (1); ES (2); AU (4); BE (5)