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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01263015




Registration number
NCT01263015
Ethics application status
Date submitted
16/12/2010
Date registered
20/12/2010
Date last updated
4/04/2018

Titles & IDs
Public title
A Trial Comparing GSK1349572 50mg Plus Abacavir/Lamivudine Once Daily to Atripla (Also Called The SINGLE Trial)
Scientific title
A Randomized, Double-Blind Study of the Safety and Efficacy of GSK1349572 Plus Abacavir/Lamivudine Fixed-Dose Combination Therapy Administered Once Daily Compared to Atripla Over 96 Weeks in HIV-1 Infected Antiretroviral Therapy Naive Adult Subjects
Secondary ID [1] 0 0
114467
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Infection, Human Immunodeficiency Virus I 0 0
Condition category
Condition code
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Dolutegravir
Treatment: Drugs - Atripla
Treatment: Drugs - Abacavir/Lamivudine
Treatment: Drugs - Abacavir/Lamivudine Placebo
Treatment: Drugs - Dolutegravir placebo
Treatment: Drugs - Atripla placebo

Experimental: Dolutegravir (N=~394): - Dolutegravir 50mg once daily + abacavir/lamivudine as the fixed-dose combination once daily + Atripla placebo once daily

Active Comparator: Atripla (N=~394): - Atripla once daily + Dolutegravir placebo once daily + abacavir/lamivudine as the fixed-dose combination placebo once daily


Treatment: Drugs: Dolutegravir
Dolutegravir (also known as GSK1349572) 50 mg taken once daily

Treatment: Drugs: Atripla
Atripla once daily on an empty stomach

Treatment: Drugs: Abacavir/Lamivudine
taken once daily; also known as EPZICOM

Treatment: Drugs: Abacavir/Lamivudine Placebo
matching placebo taken once daily

Treatment: Drugs: Dolutegravir placebo
matching placebo taken once daily

Treatment: Drugs: Atripla placebo
matching placebo taken once daily on an empty stomach

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Proportion of Subjects Responding Based on Plasma HIV-1 RNA <50 c/mL at Week 48 - The percentage of participants with plasma HIV-1 RNA <50 c/mL at Week 48 was assessed. Plasma samples were collected for the quantitative assessment of HIV-1 RNA based on the Missing, Switch, or Discontinuation equals Failure (MSDF) algorithm,as codified by the Food and Drug Administration's Snapshot algorithm. This algorithm treats all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigationl product prior to the visit window) as non-responders, as well as participants who switched their concomitant antiretroviral therapy (ART) in certain scenarios. Since changes in ART were not permitted in this protocol, all such participants who changed ART were to be considered non-responders. Otherwise, virologic success or failure was to be determined by the last available HIV-1 RNA assessment while the participant was on treatment within the visit of interest window.
Timepoint [1] 0 0
Week 48
Secondary outcome [1] 0 0
Time to Viral Suppression (<50 c/mL) - Viral suppression is defined as the first viral load value<50 c/mL. The Kaplan-Meier method was used to estimate time to viral suppression, defined as the time from the first dose of study treatment until the first viral load value <50 c/mL was reached. Participants who withdrew for any reason without having suppressed prior to the analysis were censored.
Timepoint [1] 0 0
From Baseline until Week 144) (average of 877.4 days for DTG; average of 788.8 study days for EFV/TDF/FTC)
Secondary outcome [2] 0 0
Percentage of Participants With Plasma Human Immunodeficiency Virus -1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 96 and Week 144 - The percentage of participants with plasma HIV-1 RNA <50 c/mL at Week 96 and Week 144 was assessed. Plasma samples were collected for the quantitative assessment of HIV-1 RNA based on the Missing, Switch, or Discontinuation equals Failure (MSDF) algorithm,as codified by the Food and Drug Administration's Snapshot algorithm. This algorithm treats all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigationl product prior to the visit window) as non-responders, as well as participants who switched their concomitant antiretroviral therapy (ART) in certain scenarios. Since changes in ART were not permitted in this protocol, all such participants who changed ART were to be considered non-responders. Otherwise, virologic success or failure was to be determined by the last available HIV-1 RNA assessment while the participant was on treatment within the visit of interest window.
Timepoint [2] 0 0
Week 96 and Week 144
Secondary outcome [3] 0 0
Number of Participants With a Confirmed Plasma HIV-1 RNA Level >=1000 c/mL at or After Week 16 and Before Week 24, or a Confirmed Plasma HIV-1 RNA Level >=200 c/mL at or After Week 24 - Data are presented as Kaplan Meier estimates of virologic failure (VF), defined as a confirmed plasma HIV-1 RNA level >=1000 c/mL at or after Week 16 and before Week 24, or a confirmed plasma HIV-1 RNA level >=200 c/mL at or after Week 24. A plasma HIV-1 RNA value was considered to be confirmed failure if a consecutive measurement satisfied the same failure criterion. The number of participants who experienced autoimmune deficiency syndrome (AIDS) Clinical Trials Group (ACTG) VFs was measured. For participants who withdrew from the study/were not documented to have reached confirmed VF at the cut off date of the Week 48 analysis, time to VF was to be censored at the planned visit week of the last measured plasma HIV-1 RNA sample. Data for participants who missed three consecutive scheduled plasma HIV-1 RNA measurements were to be censored at the planned visit week of the last assessment prior to the 3 consecutive missed visits.
Timepoint [3] 0 0
From Baseline until Week 144) (average of 877.4 days for DTG; average of 788.8 study days for EFV/TDF/FTC)
Secondary outcome [4] 0 0
Change From Baseline in Plasma HIV-1 RNA at Weeks 2, 4, 8, 12, 16, 24, 32, 40,48, 60, 72, 84, 96, 108, 120, 132 and 144 - Blood samples were collected for the measurement of HIV-1 RNA in plasma. Changes from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants available at the indicated time points were assessed (represented by n=X, X in the category titles).
Timepoint [4] 0 0
Baseline and at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132 and 144
Secondary outcome [5] 0 0
Change From Baseline in CD4+ Cell Counts at Week 144 - Cluster of differentiation (CD4) lymphocyte cells (also called T-cells or T-helper cells) are the primary targets of HIV. The CD4 count and the CD4 percentage mark the degree of immunocompromise. The CD4 count is used to stage the patient's disease, determine the risk of opportunistic illnesses, assess prognosis, and guide decisions about when to start antiretroviral therapy. Change from Baseline was calculated as the Week 144 value minus the Baseline value. The least squares mean is the estimated mean change from Baseline in CD4+ cell counts at Week 144 calculated from a repeated measures model including the following covariates: treatment, visit, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, treatment*visit interaction, Baseline HIV-1 RNA*visit interaction, and Baseline CD4+ cell count*visit interaction. No assumptions were made about the correlations between a participant's readings of CD4+, i.e., the correlation matrix for within-participant errors is unstructured.
Timepoint [5] 0 0
Baseline and Week 144
Secondary outcome [6] 0 0
Change From Baseline in CD4+ Cell Counts at Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132 and 144 - CD4 lymphocyte cells (also called T-cells or T-helper cells) are the primary targets of HIV. The CD4 count and the CD4 percentage mark the degree of immunocompromise. The CD4 count is used to stage the patient's disease, determine the risk of opportunistic illnesses, assess prognosis, and guide decisions about when to start antiretroviral therapy. Change from Baseline was calculated as the value at Indicated visit minus the Baseline value. Only those participants available at the indicated time points were assessed (represented by n=X, X in the category titles).
Timepoint [6] 0 0
Baseline and Week 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132 and 144
Secondary outcome [7] 0 0
Number of Participants With the Indicated Post-baseline HIV-associated Conditions and Progression, Excluding Recurrences at Week 144 - Clinical disease progression (CDP) was assessed according to the Centers for Disease Control and Prevention (CDC) HIV-1 classification system. Category (CAT) A: one or more of the following conditions (CON), without any CON listed in Categories B and C: asymptomatic HIV infection, persistent generalized lymphadenopathy, acute (primary) HIV infection with accompanying illness or history of acute HIV infection. CAT B: symptomatic CON that are attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or that are considered by physicians to have a clinical course or to require management that is complicated by HIV infection; and not included among CON listed in clinical CAT C. CAT C: the clinical CON listed in the AIDS surveillance case definition. Indicators of CDP were defined as: CDC CAT A at Baseline (BS) to a CDC CAT C event (EV); CDC CAT B at BS to a CDC CAT C EV; CDC CAT C at BS to a new CDC CAT C EV; or CDC CAT A, B, or C at BS to death.
Timepoint [7] 0 0
From Baseline until Week 144
Secondary outcome [8] 0 0
Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities at Week144 - All Grade 1 to 4 post-Baseline-emergent chemistry toxicities included alanine aminotransferase (ALT), albumin, alkaline phosphatase (ALP), asparate aminotransferase (AST), carbon dioxide (CO2) content/bicarbonate, cholesterol, creatine kinase (CK), creatinine, hyperglycemia, hyperkalemia, hypernatremia, hypoglycemia, hypokalemia, hyponatremia, low density lipoprotein (LDL) cholesterol calculation, lipase, phosphorus inorganic, total bilirubin, and triglycerides. All Grade 1 to 4 post-Baseline-emergent hematology toxities included hemoglobin, platelet count, total neutrophils, and white blood cell count. The Division of AIDS (DAIDS) defined toxicity grades as follows: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening; Grade 5, death.
Timepoint [8] 0 0
From Baseline until Week 144
Secondary outcome [9] 0 0
Number of Participants With the Indicated Genotypic Resistance With Virological Failure (VF) Through 144 - Whole blood samples were collected from participants to provide plasma for storage samples for potential viral genotypic and phenotypic analyses. Participants with confirmed virological failure (confirmed HIV-1 RNA >=50 copies/mL throughout the study and/or confirmed HIV-1 RNA >=200 copies/mL at Week 144) had plasma samples tested for HIV-1 RT genotype and HIV-1 integrase genotype from Baseline samples and from samples collected at the time of virological failure. Genotype testing was conducted at Day 1 and at the time of suspected protocol-defined virological failure (PDVF). A genotyping assessment was made of change across all amino acids within the integrase (IN)-encoding region, with particular attention paid to specific amino acid changes associated with the development of resistance to RAL, ELV, or DTG.
Timepoint [9] 0 0
Through Week 144
Secondary outcome [10] 0 0
Change From Baseline in the Symptom Bother Score (SBS) at Week 4 Through Week 48 - The Symptom Distress Module (SDM) is a 20-item, self-reported questionnaire measuring the presence/perceived distress linked to symptoms associated with HIV/its treatments. Developed with support from the AIDS Clinical Trials Group of the U.S. National Institute of Allergy and Infectious Diseases, it has demonstrated construct validity and has shown strong associations with physical/mental health summary scores and with disease severity. The SDM consists of 2 main scores: symptom count and the SBS, ranging from 0 (best) to 80 (worst) and based on the degree of bother that each symptom present posed. The SBS was calculated by adding the 20 individual bother item scores, which were calculated as: 0, "I do not have this symptom"; 1, "It doesn't bother me"; 2, "It bothers me a little"; 3, "It bothers me"; 4, "It bothers me a lot." Estimates are calculated from an analysis of covariance (ANCOVA) model adjusting for age, sex, race, Baseline (BL) viral load, BL CD4+ cell count, and BL SBS.
Timepoint [10] 0 0
Baseline and Week 4 through 48

Eligibility
Key inclusion criteria
- Screening plasma HIV-1 RNA =1000 c/mL

- Antiretroviral-naïve (= 10 days of prior therapy with any antiretroviral agent
following a diagnosis of HIV-1 infection)

- Ability to understand and sign a written informed consent form

- Willingness to use approved methods of contraception to avoid pregnancy (women of
child bearing potential only)

- Age equal to or greater than 18 years

- A negative HLAB*5701 allele assessment
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Women who are pregnant or breastfeeding;

- Active Center for Disease and Prevention Control (CDC) Category C disease

- Hepatic impairment

- HBV co-infection

- Anticipated need for HCV therapy during the study

- Allergy or intolerance to the study drugs or their components or drugs of their class

- Malignancy within the past 5 years

- Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening

- Treatment with radiation therapy, cytotoxic chemotherapeutic agents or any
immunomodulator within 28 days of Screening

- Exposure to an agent with documented activity against HIV-1 in vitro or an
experimental vaccine or drug within 28 days of first dose of study medication

- Primary viral resistance in the Screening result

- Verified Grade 4 laboratory abnormality

- ALT >5 xULN

- ALT = 3xULN and bilirubin = 1.5xULN (with >35% direct bilirubin);

- Estimated creatinine clearance <50 mL/min

- Recent history (=3 months) of upper or lower gastrointestinal bleed

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Darlinghurst, Sydney
Recruitment hospital [2] 0 0
GSK Investigational Site - Carlton
Recruitment hospital [3] 0 0
GSK Investigational Site - North Fitzroy
Recruitment hospital [4] 0 0
GSK Investigational Site - Prahran
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst, Sydney
Recruitment postcode(s) [2] 0 0
3053 - Carlton
Recruitment postcode(s) [3] 0 0
3078 - North Fitzroy
Recruitment postcode(s) [4] 0 0
3181 - Prahran
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
District of Columbia
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
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Iowa
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United States of America
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Maryland
Country [11] 0 0
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Massachusetts
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Minnesota
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Nebraska
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Nevada
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New Jersey
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New York
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North Carolina
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Ohio
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Oregon
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Pennsylvania
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Rhode Island
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South Carolina
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Texas
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Utah
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Belgium
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Antwerpen
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Belgium
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Bruxelles
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Belgium
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Gent
Country [28] 0 0
Belgium
State/province [28] 0 0
Liege
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Canada
State/province [29] 0 0
Alberta
Country [30] 0 0
Canada
State/province [30] 0 0
British Columbia
Country [31] 0 0
Canada
State/province [31] 0 0
Manitoba
Country [32] 0 0
Canada
State/province [32] 0 0
Ontario
Country [33] 0 0
Canada
State/province [33] 0 0
Quebec
Country [34] 0 0
Denmark
State/province [34] 0 0
Hvidovre
Country [35] 0 0
Denmark
State/province [35] 0 0
Koebenhavn
Country [36] 0 0
Denmark
State/province [36] 0 0
Odense
Country [37] 0 0
France
State/province [37] 0 0
Nice
Country [38] 0 0
France
State/province [38] 0 0
Orléans Cedex 2
Country [39] 0 0
France
State/province [39] 0 0
Paris Cedex 20
Country [40] 0 0
France
State/province [40] 0 0
Saint Denis Cedex 01
Country [41] 0 0
France
State/province [41] 0 0
Strasbourg cedex
Country [42] 0 0
France
State/province [42] 0 0
Tourcoing cedex
Country [43] 0 0
Germany
State/province [43] 0 0
Baden-Wuerttemberg
Country [44] 0 0
Germany
State/province [44] 0 0
Bayern
Country [45] 0 0
Germany
State/province [45] 0 0
Hessen
Country [46] 0 0
Germany
State/province [46] 0 0
Niedersachsen
Country [47] 0 0
Germany
State/province [47] 0 0
Nordrhein-Westfalen
Country [48] 0 0
Germany
State/province [48] 0 0
Berlin
Country [49] 0 0
Germany
State/province [49] 0 0
Hamburg
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Italy
State/province [50] 0 0
Emilia-Romagna
Country [51] 0 0
Italy
State/province [51] 0 0
Lazio
Country [52] 0 0
Italy
State/province [52] 0 0
Liguria
Country [53] 0 0
Italy
State/province [53] 0 0
Lombardia
Country [54] 0 0
Italy
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Toscana
Country [55] 0 0
Netherlands
State/province [55] 0 0
Rotterdam
Country [56] 0 0
Netherlands
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Utrecht
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Romania
State/province [57] 0 0
Bucharest
Country [58] 0 0
Romania
State/province [58] 0 0
Constanta
Country [59] 0 0
Spain
State/province [59] 0 0
Asturias
Country [60] 0 0
Spain
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(Móstoles) Madrid
Country [61] 0 0
Spain
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Alcala de Henares
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Spain
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Alicante
Country [63] 0 0
Spain
State/province [63] 0 0
Badalona
Country [64] 0 0
Spain
State/province [64] 0 0
Barcelona
Country [65] 0 0
Spain
State/province [65] 0 0
Basurto/Bilbao
Country [66] 0 0
Spain
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Elche (Alicante)
Country [67] 0 0
Spain
State/province [67] 0 0
Granada
Country [68] 0 0
Spain
State/province [68] 0 0
Granollers (Barcelona)
Country [69] 0 0
Spain
State/province [69] 0 0
La Laguna (Santa Cruz De Tenerife)
Country [70] 0 0
Spain
State/province [70] 0 0
Logroño
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Spain
State/province [71] 0 0
Madrid
Country [72] 0 0
Spain
State/province [72] 0 0
Marid
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Spain
State/province [73] 0 0
Murcia
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Spain
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Málaga
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Spain
State/province [75] 0 0
Palma de Mallorca
Country [76] 0 0
Spain
State/province [76] 0 0
Sabadell (Barcelona)
Country [77] 0 0
Spain
State/province [77] 0 0
San Sebastián
Country [78] 0 0
Spain
State/province [78] 0 0
Santiago de Compostela
Country [79] 0 0
Spain
State/province [79] 0 0
Sevilla
Country [80] 0 0
Spain
State/province [80] 0 0
Valencia
Country [81] 0 0
Spain
State/province [81] 0 0
Vigo ( Pontevedra)
Country [82] 0 0
United Kingdom
State/province [82] 0 0
London
Country [83] 0 0
United Kingdom
State/province [83] 0 0
Birmingham
Country [84] 0 0
United Kingdom
State/province [84] 0 0
Liverpool
Country [85] 0 0
United Kingdom
State/province [85] 0 0
Tooting, London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
ViiV Healthcare
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Shionogi
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
GlaxoSmithKline
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this trial is to assess the non-inferior antiviral activity of GSK1349572 50
mg plus Abacavir/Lamivudine once daily versus Efavirenz/Emtricitabine/Tenofovir disoproxil
fumarate (ATRIPLA® a trade mark of Bristol-Myers Squibb and Gilead Sciences LLC) over 48
weeks; non-inferiority will also be tested at Week 96. This study will be conducted in HIV-1
infected ART-naïve adult subjects. Long term antiviral activity, tolerability, safety, and
development of viral resistance will be evaluated.
Trial website
https://clinicaltrials.gov/show/NCT01263015
Trial related presentations / publications
Brinson C, Walmsley S, Arasteh K, et al. Dolutegravir treatment response and safety by key subgroups in treatment naive HIV-infected individuals. Published at: Conference on Retroviruses and Opportunistic Infections - 20th Annual; March 3-6, 2013; Atlanta, GA.
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
ViiV Healthcare
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications