Clinical Trials

Date: 2012-07-11

Type of information: Results

phase: 3

Announcement: initial results

Company: Shionogi-ViiV Healthcare (Japan - UK - USA)

Product: dolutegravir-based regimen

Action mechanism:

  • S/GSK1349572 (dolutegravir) is an investigational integrase inhibitor (INI) currently in development by Shionogi-ViiV Healthcare LLC for the treatment of HIV. Dolutegravir does not require an additional \'booster\' drug be added to the regimen. Integrase inhibitors block HIV replication by preventing the viral DNA from integrating into the genetic material of human immune cells (T-cells). This step is essential in the HIV replication cycle and is also responsible for establishing chronic infection. Given the stage of development of this investigational HIV therapy, the full picture of the efficacy and safety of dolutegravir has not been conclusively determined.

Disease: HIV-Aids

Therapeutic area: Infectious diseases


Trial details:

  • SINGLE is an ongoing double blind, double dummy study designed to compare the efficacy and safety of two antiretroviral regimens: dolutegravir 50mg plus abacavir/lamivudine (Kivexa®/Epzicom®) versus Atripla® (tenofovir/emtricitabine/efavirenz). The primary endpoint was the proportion of study participants with undetectable HIV-1 RNA (<50c/mL) at 48 weeks; 414 treatment-naive study participants were randomised and exposed to the dolutegravir-based  regimen and 419 to the Atripla arm.  Overall, 2% of subjects on the dolutegravir-based regimen discontinued due to adverse events vs. 10% of those receiving the Atripla regimen. The most common drug related adverse events on Atripla were in the nervous system System Organ Class (reported by 41% of Atripla recipients, vs. 15% of participants receiving the dolutegravir-based regimen), while the most common drug related adverse events on the dolutegravir-based  regimen were in the gastrointestinal system organ class (reported by 22% of subjects receiving the dolutegravir-based  regimen and 22% of subjects receiving Atripla®)

Latest news:

  • Shionogi-ViiV Healthcare, joint venture between Shionogi and ViiV Healthcare, a global company with a sole focus on HIV established in 2009 by GSK and Pfizer, announced that initial results have been received from the Phase III SINGLE (ING114467) study of the investigational integrase inhibitor dolutegravir in treatment-naive adults with HIV-1. The study demonstrated superiority of the dolutegravir-based regimen compared to the single tablet regimen Atripla®. The primary objectivSINGLE e for is to demonstrate the antiviral activity of dolutegravir plus abacavir/lamivudine once-daily therapy compared to Atripla® over 48 weeks. At 48 weeks, 88% of study participants on the dolutegravir regimen were virologically suppressed (<50 copies/mL) vs. 81% of participants on the single tablet regimen Atripla® [difference and 95% CI; 7.4% (+2.5% to +12.3%); difference in the primary endpoint was statistically significant, p=0.003]. Differences in efficacy were primarily driven by a higher rate of discontinuation due to adverse events on the Atripla arm. The SINGLE study was designed to demonstrate non-inferiority of the dolutegravir-based regimen versus Atripla®  and the primary analysis met this criterion.  Statistical superiority was concluded as part of a subsequent, pre-specified testing procedure. Full results of this study, including key secondary endpoints, will be presented at upcoming scientific meetings. SINGLE is the second of four Phase III studies that are due to be reported in 2012. Data from the clinical trial SPRING-2 (ING113086) were announced in April 2012. Data from VIKING-3 (ING112574) and SAILING (ING111762) in treatment-experienced patients will be received later this year and will allow further characterization of the profile of dolutegravir. These studies are designed to support a future regulatory filing for dolutegravir.

Is general: Yes