A Dose Ranging Trial of GSK1349572 and 2 NRTI in HIV-1 Infected, Therapy Naive Subjects
Condition: Infection, Human Immunodeficiency Virus
MeSH terms: Infections; Acquired Immunodeficiency Syndrome; HIV Infections
Intervention: GSK1349572; efavirenz
Intervention description: investigational HIV-1 integrase inhibitor; approved therapy for HIV-1 infection, used as an internal study control
Intervention MeSH terms: Efavirenz; Dolutegravir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 208.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: GSK1349572; emtricitabine; tenofovir; efavirenz; abacavir; antiretroviral therapy naive; dose selection; HIV-1 Infection; integrase inhibitor; HIV infection; once daily; lamivudine

Summary:

      This Phase IIb study in HIV-infected antiretroviral naive subjects will select an optimal
      once daily dose of GSK1349572 from a range of doses for future evaluation.
    

Eligibility criteria:

        Inclusion Criteria:

          -  HIV-1 infected male or female adults at least 18 years of age. Women capable of
             becoming pregnant must use appropriate contraception during the study (as defined by
             the protocol);

          -  HIV-1 infection with a screening plasma HIV-1 RNA greater than or equal to
             1000copies/mL;

          -  CD4+ cell count greater than or equal to 200cells/mm3 (or higher as local guidelines
             dictate);

          -  ART-naive (less than or equal to 10 days of prior therapy with any antiretroviral
             agent). Any previous exposure to an HIV integrase inhibitor other than GSK1349572 will
             be exclusionary.

          -  No evidence of viral resistance to any antiretroviral drug indicative of primary
             transmitted resistance at screening;

          -  Able to understand and comply with protocol requirements;

          -  Able to provide written informed consent prior to screening;

          -  French subjects: In France, a subject will be eligible for inclusion in this study
             only if either affiliated to or a beneficiary of a social security category.

        Note: Subjects starting abacavir as part of the NRTI backbone must have been screened and
        be negative for the HLA-B*5701 allele.

        Exclusion Criteria:

          -  Any pre-existing or serious mental or physical disorder which could compromise ability
             to comply with the protocol or compromise subject safety;

          -  Women who are pregnant or breastfeeding;

          -  An active AIDS-defining condition at the screening visit;

          -  Previous participation in an experimental drug and/or vaccine trial(s) within 30 days
             or 5 half-lives;

          -  History of clinically relevant pancreatitis or hepatitis within the previous 6 months,
             including HBsAg positive result. Asymptomatic HCV infection will not be exclusionary,
             however subject who will require HCV therapy during the trial should be excluded. Any
             subject with a history of liver cirrhosis with or without hepatitis viral co-infection
             will be excluded.

          -  Any condition which could interfere with the absorption, distribution, metabolism or
             excretion of the drug;

          -  Any acute or Grade 4 laboratory abnormality at screening;

          -  History of upper gastrointestinal bleed and/or subjects with active peptic ulcer
             disease;

          -  Estimated creatinine clearance <50 mL/min;

          -  Alanine aminotransferase (ALT) greater than or equal to 5 times ULN;

          -  Alanine aminotransferase (ALT) greater than or equal to 3xULN and bilirubin greater
             than or equal to 1.5xULN (with >35% direct bilirubin);

          -  Lipase greater than or equal to 3xULN;

          -  Hemoglobin < 100 g/L(10 g/dL);

          -  History of allergy to the study drugs or their components or drugs of their class;

          -  Treatment with radiation therapy, cytotoxic chemotherapeutic agents, any agents with
             activity against HIV-1 or immunomodulators within 28 days prior to screening;

          -  Treatment with an HIV-1 immunotherapeutic vaccine within 90 days prior to screening;

          -  History of protocol-defined cardiac diseases;

          -  Personal or family history of prolonged QT syndrome;

          -  Any clinically significant finding, as specified in the protocol, on
             electrocardiograph (ECG);

          -  Significant blood loss in excess of 500 mL within a 56 day period prior to screening
             visit;

          -  Immunization within 30 days prior to first dose of investigational product;

          -  French subjects: The subject has participated in any study using an investigational
             drug during the previous 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 or the subject will participate simultaneously in another
             clinical study.