A Study of GSK1349572 Versus Raltegravir (RAL) With Investigator Selected Background Regimen in Antiretroviral-Experienced, Integrase Inhibitor-Naive Adults
Condition: Infection, Human Immunodeficiency Virus; HIV Infections
MeSH terms: Infections; Communicable Diseases; HIV Infections; Acquired Immunodeficiency Syndrome
Intervention: GSK1349572; Raltegravir; GSK1349572 Placebo; Raltegravir Placebo
Intervention description: 50mg once daily; 400mg twice daily; Inactive placebo tablet once daily; Inactive placebo tablet twice daily
Intervention MeSH terms: Raltegravir Potassium; Dolutegravir
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 724.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ART-experienced; Integrase inhibitor; Raltegravir; GSK1349572; Integrase inhibitor naive

Summary:

      ING111762 is a 48 week, randomized, double-blind, active-controlled, multicenter, parallel
      group, non-inferiority study. The study will be conducted in at least 688 HIV-1 infected
      antiretroviral experienced, integrase-naïve subjects. Subjects will be randomized 1:1 to
      receive GSK1349572 50 mg once daily or raltegravir (RAL) 400 mg twice daily, each added to an
      investigator selected background regimen consisting of at least one fully active agent plus
      no more than one second single agent which may or may not be active. Antiviral activity,
      safety, pharmacokinetics (PK), and development of viral resistance will be evaluated.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Antiretroviral therapy (ART)-experienced, Human Immunodeficiency Virus (HIV) -1
             infected 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 as documented by HIV-1 RNA >400 copies/mL (c/mL) at Screening and with
             at least one consecutive HIV-1 RNA >400 c/mL within the four months prior to Screening
             (unless the Screening HIV-1 RNA is > 1000 c/mL where no additional plasma HIV-1 RNA
             assessment is needed).

          -  Have documented resistance (via Screening resistance test) to two or more different
             classes of antiretroviral agents. For subjects off ART for at least one month, if
             Screening resistance results provide a fully active agent and do not show two class
             resistance then historical resistance results from the subject's most recent
             resistance testing may be used, following consultation with the study virologist and
             /or medical monitor.

          -  Integrase inhibitor (INI)-naïve, defined as no prior exposure to any INI (e.g. RAL,
             elvitegravir, or GSK1349572).

          -  Able to provide written informed consent prior to Screening.

          -  French subjects: In France, subjects will be eligible for inclusion in this study only
             if either affiliated to or a beneficiary of a social security category.

        Exclusion Criteria:

          -  Screening resistance test result indicates no fully active antiviral agents are
             available for design of the background regimen.

          -  Subject-virus does not yield results using genotype/phenotype/tropism at Screening
             (assay data is essential for eligibility determination).

          -  Women who are breastfeeding.

          -  Any evidence of an active AIDS-defining condition (except cutaneous Kaposi's sarcoma
             not requiring systemic therapy or CD4+ <200c/mm3).

          -  Subjects with moderate to severe hepatic impairment as defined by Child-Pugh
             classification.

          -  Recent history (less than or equal to 3 months) of upper or lower gastrointestinal
             bleed, with the exception of anal or rectal bleeding.

          -  Anticipated need for hepatitis C therapy during the study.

          -  History or presence of allergy or intolerance to the study drugs or their components
             or drugs of their class.

          -  History of malignancy within the past 5 years or ongoing malignancy other than
             cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous
             squamous cell carcinoma; other localized malignancies require agreement between the
             investigator and study medical monitor for inclusion of the subject.

          -  Treatment with an HIV-1 immunotherapeutic vaccine within 90 days prior to Screening.

          -  Treatment with any of the following agents within 28 days of Screening: radiation
             therapy, cytotoxic chemotherapeutic agents, any immunomodulator.

          -  Treatment with any agent, other than licensed ART, which has documented activity
             against HIV-1 in vitro within 28 days of first dose of investigational product.

          -  Exposure to an experimental drug and/or experimental vaccine within either 28 days, 5
             half-lives of the test agent, or twice the duration of the biological effect of the
             experimental test agent - whichever is longer, prior to the first dose of IP.

          -  French subjects recruited at sites in France will be excluded if the subject has
             participated in any study using an investigational drug and/or vaccine 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 or the
             subject plans to participate simultaneously in another clinical study.

          -  Any acute or verified Grade 4 laboratory abnormality.

          -  Alanine aminotransferase (ALT) >5 times the upper limit of normal (ULN).

          -  ALT greater than or equal to 3xULN and bilirubin greater than or equal to 1.5xULN
             (with >35% direct bilirubin).