Dolutegravir Compared to Darunavir/Ritonavir , Each in Combination With Dual Nucleoside Reverse Transcriptase Inhibitors (NRTIs) in ART-naive Subjects

• Status: Completed
• Trial end date: 2016-12-26
• Target enrollment: 0
• Participant gender: All

Summary

This study will be conducted in approximately 468 HIV-1 infected antiretroviral therapy (ART)-naïve subjects. Subjects will be randomized 1:1 to receive dolutegravir (DTG) 50 mg once daily (approximately 234 subjects) or darunavir/ritonavir (DRV/r) 800 mg/100 mg once daily (approximately 234 subjects), each in combination with fixed-dose dual nucleoside reverse transriptase inhibitor (NRTI) therapy (either abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC). Subjects will be stratified by screening HIV-1 RNA and background NRTI selection. The primary analysis will take place after the last subject completes 48 weeks on therapy; an additional analysis will be conducted after the last subject completes Week 96 on study.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: ViiV Healthcare
• Collaborator: GlaxoSmithKline
• Treatments: Darunavir; Dolutegravir; Reverse Transcriptase Inhibitors; Ritonavir; Tenofovir

Criteria

Inclusion Criteria:

• HIV-1 infected adults greater than or equal to 18 years of age. Females are eligible to enter and participate in the study if she is (1) non-childbearing potential, (2) child bearing potential with negative pregnancy test at screening and Day 1 and agrees to use protocol-specified methods of birth control while on study.

• HIV-1 infection with a screening plasma HIV-1 RNA greater than or equal to 1000copies/mL

• Antiretroviral-naïve (less than or equal to 10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection)

• Signed and dated written informed consent is obtained from the subject or the subject's legal representative prior to screening

Exclusion Criteria:

• Women who are pregnant or breastfeeding

• Any evidence of an active Centers for Disease and Prevention Control (CDC) Category C disease [CDC, 1993], except cutaneous Kaposi's sarcoma not requiring systemic therapy

• Subjects with moderate to severe hepatic impairment (Class B or C) as determined by Child-Pugh classification

• Anticipated need for Hepatitis C virus (HCV) 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 the Study medical monitor for inclusion of the subject

• Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening

• Treatment with any of the following agents within 28 days of Screening: radiation therapy; cytotoxic chemotherapeutic agents; any immunomodulators

• Treatment with any agent, except recognized ART as allowed above, with documented activity against HIV-1 in vitro within 28 days of first dose of investigational product

• Exposure to an experimental drug or experimental vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of investigational product

• Any evidence of primary viral resistance based on the presence of any major resistance-associated mutation [IAS-USA, 2010] in the Screening result or, if known, any historical resistance test result

• Any verified Grade 4 laboratory abnormality. Any acute laboratory abnormality at Screening, which, in the opinion of the Investigator, would preclude the subject's participation in the study of an investigational compound is exclusionary

• Alanine aminotransferase (ALT) greater than 5 times the upper limit of normal

• ALT greater than 3 times the upper limit of normal and bilirubin greater than or equal to 1.5 times the upper limit of normal (with greater than 35% direct bilirubin)

• Subject has creatinine clearance of less than 50 mL/min via Cockroft-Gault method

• Recent history (less than or equal to 3 months) of any upper or lower gastrointestinal bleed, with the exception of anal or rectal bleeding