A Dose Ranging Trial of GSK1349572 and 2 NRTI in HIV-1 Infected, Therapy Naive Subjects

Trial end date:
Target enrollment:
Participant gender:
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.
Phase 2
Accepts Healthy Volunteers?
Lead Sponsor:
ViiV Healthcare
Integrase Inhibitors
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

- CD4+ cell count greater than or equal to 200cells/mm3 (or higher as local guidelines

- 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

- 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

- 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.