A Pilot Study Assessing the Integrase Inhibitor GSK1349572 in HIV-infected Persons With Virus Resistant to Raltegravir
Condition: Infection, Human Immunodeficiency Virus
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Intervention: GSK1349572 (Cohort I); GSK1349572 (Cohort II)
Intervention description: 50 mg once daily; 50 mg twice daily
Intervention MeSH terms: Dolutegravir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 51.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: treatment experienced; HIV Infection; raltegravir resistance; GSK1349572; optimized background regimen; integrase inhibitor

Summary:

      Integrase is an enzyme produced by HIV so that the virus can multiply in the human body.
      GSK1349572 is a new drug in the integrase inhibitor class that prevents the enzyme from
      working properly and therefore prevents the virus from multiplying.

      GSK1349572 has shown to be effective against viruses in a short-term monotherapy study in
      adults with no previous exposure to integrase inhibitors. The purpose of this study is to
      determine whether GSK1349572 is effective in the treatment of HIV-infected patients who no
      longer respond to treatment with the approved integrase inhibitor raltegravir and carry
      viruses with resistance to this drug. The safety and efficacy of GSK1349572 50mg once daily
      in combination with the background HIV drugs previously administered (unless discontinuation
      of a particular drug is required) will be assessed over 10 days (functional monotherapy
      phase), followed by the evaluation of the safety and efficacy of GSK1349572 given with a new
      optimised background regimen from Day 11 through at least Week 24.
    

Eligibility criteria:

        Inclusion Criteria:

          -  HIV-1 infected male or female adults at least 18 years of age with a plasma HIV-1 RNA
             > 1,000 copies/mL at study entry. Women capable of becoming pregnant must use
             appropriate contraception during the study (as defined by the protocol)

          -  ART-experienced (defined as on stable ART for at least the last 2 months) and is
             either currently experiencing virologic failure to RAL or experienced virologic
             failure to RAL > 8 weeks prior to Screening

          -  Must have documented RAL genotypic resistance on study entry genotype

          -  Must have documented genotypic or phenotypic resistance to at least one drug from each
             of three or more of all approved classes of ART

          -  For Cohort II, Subjects MUST be able to receive at least one fully active drug as part
             of the Day 11 optimised background regimen

          -  Willing and able to understand and provide signed and dated written informed consent
             prior to screening

        Exclusion Criteria:

          -  Any pre-existing mental, physical, or substance abuse disorder which, 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

          -  Currently take and/or anticipated need for EFV, NVP, FPV/RTV or TPV/RTV during the
             study

          -  Treatment with any of the following medications within 15 days of starting study drug,
             or anticipated to need, during the course of the study: Etravirine (unless
             co-administered with LPV/RTV or DRV/RTV), rifampin, rifabutin, phenytoin,
             phenobarbital, barbiturates, glucocorticoids, modafinil, oxcarbazepine, pioglitazone,
             troglitazone, carbamazepine, St. Johns wort

          -  Previous participation in an experimental drug and/or vaccine trial(s) within 30 days
             or 5 half-lives

          -  History of ongoing or clinically relevant pancreatitis or hepatitis within the
             previous 6 months

          -  Expected to require treatment for HCV infection during the first 24 weeks of the study

          -  Evidence of cirrhosis with or without hepatitis viral co-infection

          -  History of upper gastrointestinal bleed and/or active peptic ulcer disease

          -  Screening haemoglobin <10g/dL (100g/L)

          -  Subject suffers from a serious medical condition which could compromise the safety of
             the subject.

          -  Any condition that could interfere with the absorption, distribution, metabolism or
             excretion of the drug or render the subject unable to take oral medication

          -  Screening lipase 3 times the upper limit of normal (ULN)

          -  Any acute or Grade 4 laboratory abnormality at screening

          -  Screening alanine aminotransferase (ALT) >5xULN

          -  Screening ALT 3xULN and bilirubin 1.5xULN (with 35% direct bilirubin)

          -  Personal or family history of prolonged QT syndrome.

          -  Any clinically significant finding, as specified in the protocol, on screening or
             baseline electrocardiograph (ECG)

          -  History of allergy to the study drugs or their components or drugs of their class

          -  Treatment with radiation therapy or cytotoxic chemotherapeutic agents within 28 days
             prior to screening, or future need of treatment with these agents during the study

          -  Treatment with immunomodulators within 28 days prior to screening or subject has
             received an HIV-1 vaccine within 90 days prior to screening