A Trial Comparing GSK1349572 50mg Plus Abacavir/Lamivudine Once Daily to Atripla (Also Called The SINGLE Trial)

NCT01263015 | Completed Phase 3 Results DMC

• 1 other identifier: 114467
• Study Type: interventional
• Target: 844
• Locations: 12 countries
• Sites: 145

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.

Conditions

Infection, Human Immunodeficiency Virus I

Keywords

GSK1349572; Abacavir/Lamivudine; Treatment-naive; HIV Infection; Dolutegravir; integrase inhibitor; Atripla

Outcome Measures

Primary Outcomes (1)

• 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.

  Week 48

Secondary Outcomes (10)

• Time to Viral Suppression (<50 c/mL)

  From Baseline until Week 144) (average of 877.4 days for DTG; average of 788.8 study days for EFV/TDF/FTC)

• 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

  Week 96 and Week 144

• 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

  From Baseline until Week 144) (average of 877.4 days for DTG; average of 788.8 study days for EFV/TDF/FTC)

• 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

  Baseline and at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132 and 144

• Change From Baseline in CD4+ Cell Counts at Week 144

  Baseline and Week 144

Study Arms (2)

Dolutegravir (N=~394):

EXPERIMENTAL

Dolutegravir 50mg once daily + abacavir/lamivudine as the fixed-dose combination once daily + Atripla placebo once daily

Drug: Dolutegravir; Drug: Abacavir/Lamivudine; Drug: Atripla placebo

Atripla (N=~394):

ACTIVE COMPARATOR

Atripla once daily + Dolutegravir placebo once daily + abacavir/lamivudine as the fixed-dose combination placebo once daily

Drug: Atripla; Drug: Abacavir/Lamivudine Placebo; Drug: Dolutegravir placebo

Interventions

Dolutegravir DRUG

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

Dolutegravir (N=~394):

Atripla DRUG

Atripla once daily on an empty stomach

Atripla (N=~394):

Abacavir/Lamivudine DRUG

taken once daily; also known as EPZICOM

Dolutegravir (N=~394):

Abacavir/Lamivudine Placebo DRUG

matching placebo taken once daily

Atripla (N=~394):

Dolutegravir placebo DRUG

matching placebo taken once daily

Atripla (N=~394):

Atripla placebo DRUG

matching placebo taken once daily on an empty stomach

Dolutegravir (N=~394):

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ViiV Healthcare: lead
• Shionogi: collaborator
• GlaxoSmithKline: collaborator

Study Sites (145)

GSK Investigational Site

Hobson City, Alabama, 36201, United States

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GSK Investigational Site

Little Rock, Arkansas, 72207, United States

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GSK Investigational Site

Bakersfield, California, 93301, United States

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GSK Investigational Site

Beverly Hills, California, 90211, United States

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GSK Investigational Site

Long Beach, California, 90813, United States

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GSK Investigational Site

Los Angeles, California, 90035, United States

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GSK Investigational Site

Los Angeles, California, 90069, United States

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GSK Investigational Site

Oakland, California, 94602, United States

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GSK Investigational Site

San Diego, California, 92103, United States

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GSK Investigational Site

San Francisco, California, 94109, United States

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GSK Investigational Site

San Francisco, California, 94115, United States

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GSK Investigational Site

Aurora, Colorado, 80045, United States

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GSK Investigational Site

Denver, Colorado, 80209, United States

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GSK Investigational Site

Washington D.C., District of Columbia, 20007, United States

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GSK Investigational Site

Washington D.C., District of Columbia, 20009, United States

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GSK Investigational Site

Washington D.C., District of Columbia, 20037, United States

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GSK Investigational Site

Fort Lauderdale, Florida, 33316, United States

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GSK Investigational Site

Ft. Pierce, Florida, 34982, United States

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GSK Investigational Site

Miami, Florida, 33317, United States

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GSK Investigational Site

Miami Beach, Florida, 33139, United States

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GSK Investigational Site

Orlando, Florida, 32804, United States

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GSK Investigational Site

West Palm Beach, Florida, 33401, United States

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GSK Investigational Site

Augusta, Georgia, 30912, United States

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GSK Investigational Site

Chicago, Illinois, 60612, United States

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GSK Investigational Site

Maywood, Illinois, 60153, United States

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GSK Investigational Site

Iowa City, Iowa, 52242, United States

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GSK Investigational Site

Baltimore, Maryland, 21201, United States

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GSK Investigational Site

Boston, Massachusetts, 02115, United States

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GSK Investigational Site

Springfield, Massachusetts, 01105, United States

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GSK Investigational Site

Minneapolis, Minnesota, 55404, United States

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GSK Investigational Site

Minneapolis, Minnesota, 55415, United States

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GSK Investigational Site

Omaha, Nebraska, 68106, United States

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GSK Investigational Site

Las Vegas, Nevada, 89102, United States

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GSK Investigational Site

Newark, New Jersey, 07102, United States

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GSK Investigational Site

New York, New York, 10003, United States

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GSK Investigational Site

New York, New York, 10011, United States

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GSK Investigational Site

New York, New York, 10065, United States

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GSK Investigational Site

The Bronx, New York, 10461, United States

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GSK Investigational Site

Valhalla, New York, 10595, United States

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GSK Investigational Site

Chapel Hill, North Carolina, 27514, United States

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GSK Investigational Site

Charlotte, North Carolina, 28207, United States

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GSK Investigational Site

Charlotte, North Carolina, 28209, United States

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GSK Investigational Site

Durham, North Carolina, 27710, United States

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GSK Investigational Site

Cincinnati, Ohio, 45267, United States

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GSK Investigational Site

Portland, Oregon, 97210, United States

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GSK Investigational Site

Philadelphia, Pennsylvania, 19107, United States

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GSK Investigational Site

Providence, Rhode Island, 02906, United States

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GSK Investigational Site

Charleston, South Carolina, 29425, United States

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GSK Investigational Site

Dallas, Texas, 75204, United States

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GSK Investigational Site

Dallas, Texas, 75215, United States

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GSK Investigational Site

Dallas, Texas, 75246, United States

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GSK Investigational Site

Fort Worth, Texas, 76104, United States

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GSK Investigational Site

Houston, Texas, 77030, United States

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GSK Investigational Site

Longview, Texas, 75605, United States

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GSK Investigational Site

Salt Lake City, Utah, 84102, United States

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GSK Investigational Site

Darlinghurst, Sydney, New South Wales, 2010, Australia

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GSK Investigational Site

Carlton, Victoria, 3053, Australia

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GSK Investigational Site

Fitzroy North, Victoria, 3078, Australia

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GSK Investigational Site

Prahran, Victoria, 3181, Australia

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GSK Investigational Site

Antwerp, 2000, Belgium

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GSK Investigational Site

Brussels, 1000, Belgium

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GSK Investigational Site

Ghent, 9000, Belgium

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GSK Investigational Site

Liège, 4000, Belgium

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GSK Investigational Site

Calgary, Alberta, T2R 0X7, Canada

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GSK Investigational Site

Edmonton, Alberta, T6G 2B7, Canada

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GSK Investigational Site

Vancouver, British Columbia, V6Z 2C7, Canada

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GSK Investigational Site

Vancouver, British Columbia, V6Z 2T1, Canada

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Winnipeg, Manitoba, R3A 1R9, Canada

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Toronto, Ontario, M5G 1K2, Canada

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Toronto, Ontario, M5G 2N2, Canada

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Montreal, Quebec, H2L 4P9, Canada

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GSK Investigational Site

Montreal, Quebec, H3A 1T1, Canada

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GSK Investigational Site

Montreal, Quebec, H3G 1A4, Canada

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GSK Investigational Site

Copenhagen, DK-2100, Denmark

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GSK Investigational Site

Hvidovre, 2650, Denmark

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GSK Investigational Site

Odense, 5000, Denmark

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GSK Investigational Site

Nice, 06202, France

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GSK Investigational Site

Orléans, 45067, France

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GSK Investigational Site

Paris, 75970, France

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GSK Investigational Site

Saint-Denis, 93205, France

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GSK Investigational Site

Strasbourg, 67091, France

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GSK Investigational Site

Tourcoing, 59208, France

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GSK Investigational Site

Stuttgart, Baden-Wurttemberg, 70197, Germany

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GSK Investigational Site

Munich, Bavaria, 80335, Germany

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GSK Investigational Site

Frankfurt am Main, Hesse, 60311, Germany

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GSK Investigational Site

Frankfurt am Main, Hesse, 60590, Germany

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GSK Investigational Site

Hanover, Lower Saxony, 30159, Germany

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GSK Investigational Site

Düsseldorf, North Rhine-Westphalia, 40225, Germany

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GSK Investigational Site

Essen, North Rhine-Westphalia, 45122, Germany

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GSK Investigational Site

Berlin, 12157, Germany

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GSK Investigational Site

Berlin, 13353, Germany

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GSK Investigational Site

Hamburg, 20146, Germany

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GSK Investigational Site

Ravenna, Emilia-Romagna, 48121, Italy

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GSK Investigational Site

Rome, Lazio, 00149, Italy

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GSK Investigational Site

Genoa, Liguria, 16132, Italy

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GSK Investigational Site

Bergamo, Lombardy, 24127, Italy

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GSK Investigational Site

Milan, Lombardy, 20127, Italy

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GSK Investigational Site

Bagno A Ripoli (FI), Tuscany, 50011, Italy

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GSK Investigational Site

Rotterdam, 3015 CE, Netherlands

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GSK Investigational Site

Rotterdam, 3079 DZ, Netherlands

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Utrecht, 3584 CX, Netherlands

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GSK Investigational Site

Bucharest, 021105, Romania

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GSK Investigational Site

Bucharest, 030303, Romania

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GSK Investigational Site

Constanța, 900708, Romania

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GSK Investigational Site

Oviedo, Principality of Asturias, 33011, Spain

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GSK Investigational Site

(Móstoles) Madrid, 28935, Spain

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GSK Investigational Site

Alcalá de Henares, 28805, Spain

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GSK Investigational Site

Alicante, 03010, Spain

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GSK Investigational Site

Badalona, 08916, Spain

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GSK Investigational Site

Barcelona, 08025, Spain

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GSK Investigational Site

Barcelona, 08035, Spain

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GSK Investigational Site

Barcelona, 08907, Spain

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GSK Investigational Site

Basurto/Bilbao, 48013, Spain

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GSK Investigational Site

Elche (Alicante), 03202, Spain

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GSK Investigational Site

Granada, 18014, Spain

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GSK Investigational Site

Granollers (Barcelona), 08400, Spain

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GSK Investigational Site

La Laguna (Santa Cruz de Tenerife), 38320, Spain

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GSK Investigational Site

Logroño, 26006, Spain

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GSK Investigational Site

Madrid, 28006, Spain

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GSK Investigational Site

Madrid, 28007, Spain

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GSK Investigational Site

Madrid, 28029, Spain

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GSK Investigational Site

Madrid, 28034, Spain

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GSK Investigational Site

Madrid, 28040, Spain

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GSK Investigational Site

Madrid, 28041, Spain

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GSK Investigational Site

Madrid, 28046, Spain

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GSK Investigational Site

Madrid, 28911, Spain

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GSK Investigational Site

Marid, 28040, Spain

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GSK Investigational Site

Málaga, 29010, Spain

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GSK Investigational Site

Murcia, Spain

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GSK Investigational Site

Palma de Mallorca, 07010, Spain

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GSK Investigational Site

Sabadell (Barcelona), 08208, Spain

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GSK Investigational Site

San Sebastián, 20014, Spain

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GSK Investigational Site

Santiago de Compostela, 15706, Spain

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GSK Investigational Site

Seville, 41013, Spain

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GSK Investigational Site

Valencia, 46010, Spain

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GSK Investigational Site

Valencia, 46015, Spain

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GSK Investigational Site

Valencia, 46026, Spain

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GSK Investigational Site

Vigo ( Pontevedra), 36204, Spain

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GSK Investigational Site

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

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GSK Investigational Site

Birmingham, B9 5SS, United Kingdom

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GSK Investigational Site

Liverpool, L7 8XP, United Kingdom

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GSK Investigational Site

London, NW3 2QG, United Kingdom

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GSK Investigational Site

London, SE1 7EH, United Kingdom

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GSK Investigational Site

London, SW10 9TH, United Kingdom

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GSK Investigational Site

Tooting, London, SW17 0QT, United Kingdom

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Related Publications (3)

• 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.

  BACKGROUND

• Walmsley S, Baumgarten A, Berenguer J, Felizarta F, Florence E, Khuong-Josses MA, Kilby JM, Lutz T, Podzamczer D, Portilla J, Roth N, Wong D, Granier C, Wynne B, Pappa K. Brief Report: Dolutegravir Plus Abacavir/Lamivudine for the Treatment of HIV-1 Infection in Antiretroviral Therapy-Naive Patients: Week 96 and Week 144 Results From the SINGLE Randomized Clinical Trial. J Acquir Immune Defic Syndr. 2015 Dec 15;70(5):515-9. doi: 10.1097/QAI.0000000000000790.

  PMID: 26262777 DERIVED

• Walmsley SL, Antela A, Clumeck N, Duiculescu D, Eberhard A, Gutierrez F, Hocqueloux L, Maggiolo F, Sandkovsky U, Granier C, Pappa K, Wynne B, Min S, Nichols G; SINGLE Investigators. Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection. N Engl J Med. 2013 Nov 7;369(19):1807-18. doi: 10.1056/NEJMoa1215541.

  PMID: 24195548 DERIVED

MeSH Terms

Conditions

Infections; HIV Infections

Interventions

dolutegravir; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; abacavir, lamivudine drug combination; abacavir

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)

Tenofovir; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2010
• First Posted: December 20, 2010
• Study Start: February 1, 2011
• Primary Completion: May 14, 2012
• Study Completion: December 3, 2015
• Last Updated: April 4, 2018
• Results First Posted: July 2, 2014

Record last verified: 2018-03

Locations

RO (3); BE (4); GB (7); NL (3); AU (4); IT (6); FR (6); CA (10); ES (34); DE (10); US (55); DK (3)