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

• Status: Completed
• Trial end date: 2016-12-22
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: ViiV Healthcare
• Collaborators: GlaxoSmithKline; Shionogi
• Treatments: Abacavir; Dolutegravir; Efavirenz; Emtricitabine; Integrase Inhibitors; Lamivudine; Tenofovir

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.