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

NCT ID: NCT00549198

Last Updated: 2011-04-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 392 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-06-30
• Study Completion Date: 2009-12-31

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.

Detailed Description

ViiV Healthcare is the new sponsor of this study, and GlaxoSmithKline is in the process of updating systems to reflect the change in sponsorship.

Conditions

Infection, Human Immunodeficiency Virus I; HIV Infection

Study Design

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

Study Groups

ABC/3TC + EFV

Group Type: EXPERIMENTAL

Abacavir/lamivudine and efavirenz

Intervention Type: DRUG

TDF/FTC + EFV

Group Type: ACTIVE_COMPARATOR

Tenofovir/Emtricitabine and efavirenz

Intervention Type: DRUG

Interventions

Abacavir/lamivudine and efavirenz

Intervention Type: DRUG

Tenofovir/Emtricitabine and efavirenz

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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:

1. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal); or,

2. 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):

Complete abstinence from intercourse from 2 weeks prior to administration of the investigational products, throughout the study, and for at least 2 weeks after discontinuation of all study medications Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide). Hormonal contraception will not be considered adequate for inclusion into this study Any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year.

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.

Exclusion Criteria

• 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:
• Medications with significant drug-drug interactions with efavirenz:voriconazole, terfenadine, astemizole, cisapride, ergot alkaloids (dihydroergotamine, ergonovine, ergotamine, methylergonovine), midazolam, triazolam, St. John's wort, carbamazepine, phenytoin, phenobarbital, rifampin, pimozide, bepridil
• Medications which may impact on bone mineral density: oral or systemic corticosteroids, anticonvulsants, heparin, warfarin, cyclosporine, bisphosphonates, calcitonin, parathyroid hormone, Vitamin D supplements and analogues, Calcium supplements, oestrogen or progesterone replacement (oral hormonal contraception permitted), raloxifene, tamoxifen, testosterone or anabolic steroid replacement/supplements.
• Systemic interleukins or interferons
• Subject has a history of allergy to any of the protocol-specified medications or any excipients therein.
• Subject has evidence of genotypic resistance at screening (according to central lab interpretation) or prior documented evidence of genotypic and/or phenotypic (above threshold for reduced susceptibility) resistance to any of the following drugs: efavirenz, abacavir, lamivudine, tenofovir, emtricitabine.
• Subjects who are unsuitable for DEXA scanning should be excluded, including 1) Less than three vertebra in the range of L1 to L4 that are suitable for BMD measurement by DEXA, or 2) Bilateral hip replacement.
• The subject has previously participated in an experimental drug and/or vaccine trial(s) within 60 days or 5 half-lives, or twice the duration of the biological effect of the experimental drug or vaccine - whichever is longer, prior to screening for the study.
• The subject will participate simultaneously in another clinical study.

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

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

GSK Clinical Disclosure

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Innsbruck, , Austria

GSK Investigational Site

Salzburg, , Austria

GSK Investigational Site

Vienna, , Austria

GSK Investigational Site

Vienna, , Austria

GSK Investigational Site

Bruges, , Belgium

GSK Investigational Site

Brussels, , Belgium

GSK Investigational Site

Charleroi, , Belgium

GSK Investigational Site

Ghent, , Belgium

GSK Investigational Site

Leuven, , Belgium

GSK Investigational Site

Aalborg, , Denmark

GSK Investigational Site

Aarhus N, , Denmark

GSK Investigational Site

Copenhagen, , Denmark

GSK Investigational Site

Hvidovre, , Denmark

GSK Investigational Site

Odense C, , Denmark

GSK Investigational Site

Garches, , France

GSK Investigational Site

Levallois-Perret, , France

GSK Investigational Site

Saint-Denis, , France

GSK Investigational Site

Heidelberg, Baden-Wurttemberg, Germany

GSK Investigational Site

Munich, Bavaria, Germany

GSK Investigational Site

Hamburg, City state of Hamburg, Germany

GSK Investigational Site

Hamburg, City state of Hamburg, Germany

GSK Investigational Site

Hanover, Lower Saxony, Germany

GSK Investigational Site

Hanover, Lower Saxony, Germany

GSK Investigational Site

Düsseldorf, North Rhine-Westphalia, Germany

GSK Investigational Site

Essen, North Rhine-Westphalia, Germany

GSK Investigational Site

Leipzig, Saxony, Germany

GSK Investigational Site

Berlin, State of Berlin, Germany

GSK Investigational Site

Dublin, , Ireland

GSK Investigational Site

Dublin, , Ireland

GSK Investigational Site

Ferrara, Emilia-Romagna, Italy

GSK Investigational Site

Modena, Emilia-Romagna, Italy

GSK Investigational Site

Rimini, Emilia-Romagna, Italy

GSK Investigational Site

Rome, Lazio, Italy

GSK Investigational Site

Legnano (MI, Lombardy, Italy

GSK Investigational Site

Milan, Lombardy, Italy

GSK Investigational Site

Milan, Lombardy, Italy

GSK Investigational Site

Turin, Piedmont, Italy

GSK Investigational Site

Riga, , Latvia

GSK Investigational Site

Alkmaar, , Netherlands

GSK Investigational Site

Groningen, , Netherlands

GSK Investigational Site

Rotterdam, , Netherlands

GSK Investigational Site

The Hague, , Netherlands

GSK Investigational Site

Utrecht, , Netherlands

GSK Investigational Site

Amadora, , Portugal

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Valencia, , Spain

GSK Investigational Site

Basel, , Switzerland

GSK Investigational Site

Bern, , Switzerland

GSK Investigational Site

Lausanne, , Switzerland

GSK Investigational Site

Sankt Gallen, , Switzerland

GSK Investigational Site

Zurich, , Switzerland

GSK Investigational Site

Zurich, , Switzerland

GSK Investigational Site

Manchester, Lancashire, United Kingdom

GSK Investigational Site

Woolwich, London, London, United Kingdom

GSK Investigational Site

Edinburgh, Midlothian, United Kingdom

GSK Investigational Site

Brighton, Sussex East, United Kingdom

GSK Investigational Site

Birmingham, , United Kingdom

GSK Investigational Site

Birmingham, , United Kingdom

GSK Investigational Site

Farnworth, Bolton, , United Kingdom

GSK Investigational Site

Gloucester, , United Kingdom

GSK Investigational Site

Leicester, , United Kingdom

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

Middlesbrough, , United Kingdom

GSK Investigational Site

Sheffield, , United Kingdom

Countries

Austria; Belgium; Denmark; France; Germany; Ireland; Italy; Latvia; Netherlands; Portugal; Spain; Switzerland; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 20431394 (View on PubMed)

Other Identifiers

CNA109586

Identifier Type: -

Identifier Source: org_study_id