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

• To evaluate the efficacy of the treatment arms over time using proportions of subjects maintaining plasma HIV-1 RNA <50copies/mL to Week 96 as well as change from baseline in HIV-1 RNA and increases in CD4+ cell counts [ Time Frame: 48 and 96 weeks ] [ Designated as safety issue: No ]
• To evaluate the number of participants with clinical or laboratory adverse events as a measure of safety and tolerability of the two treatment arms [ Time Frame: 48 and 96 Weeks ] [ Designated as safety issue: No ]
• To assess the development of viral resistance in subjects experiencing virological failure. [ Time Frame: 48 and 96 Weeks ] [ Designated as safety issue: No ]
• To evaluate the incidence of HIV-associated conditions. [ Time Frame: 48 and 96 Weeks ] [ Designated as safety issue: No ]

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.

ING114467 is a Phase 3 randomized, double-blind, double dummy, active-controlled, multicenter, study conducted in approximately 788 HIV-1 infected ART-naïve subjects. Subjects will be randomized 1:1 one of the following treatment arms:

GSK1349572 50 mg plus abacavir/lamivudine fixed-dose combination once daily (approximately 394 subjects)

OR

Atripla once daily (approximately 394 subjects)

Analyses will be conducted at 48 weeks and 96 weeks. Subjects randomized to receive GSK1349572 and who successfully complete 96 weeks of treatment will continue to have access to GSK1349572 plus abacavir/lamivudine fixed-dose combination through the study until it is locally available-as long as they continue to derive clinical benefit, until they meet a protocol-defined reason for discontinuation, or until development of the compound is terminated.

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

• Drug: Dolutegravir
  Dolutegravir (also known as GSK1349572) 50 mg taken once daily
• Drug: Atripla
  Atripla once daily on an empty stomach
• Drug: Abacavir/Lamivudine
  taken once daily; also known as EPZICOM
• Drug: Abacavir/Lamivudine Placebo
  matching placebo taken once daily
• Drug: Dolutegravir placebo
  matching placebo taken once daily
• Drug: Atripla placebo
  matching placebo taken once daily on an empty stomach

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

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

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

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

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

• Shionogi
• GlaxoSmithKline