Relative Bioavailability Study of Two New Dolutegravir/Abacavir/Lamivudine Fixed Dose Combination Tablets
Condition: Healthy Subjects; Infection, Human Immunodeficiency Virus
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      Dolutegravir (DTG, GSK1349572) is a next-generation integrase inhibitor (INI) currently in
      phase 3 clinical trials for human immunodeficiency virus (HIV). Fixed-dose combinations
      (FDCs) have greatly simplified the treatment of patients with HIV. While Atripla (an FDC of
      tenofovir (TDF), emtricitabine (FTC) and efavirenz (EFV)) has become the preferred first line
      regimen due in large part to its convenient presentation as a full treatment regimen in a
      single product, other options are needed. A fixed-dose combination of DTG/abacavir
      (ABC)/lamivudine (3TC) is one such opportunity.

      This is a single-center, randomized, open-label, 3-period crossover study in healthy adult
      subjects to evaluate the single-dose relative bioavailability of two experimental oral DTG 50
      mg/ABC 600 mg/3TC 300 mg FDC tablet formulations compared to co-administration of the
      separate tablet formulations (DTG 50 mg tablet and EPZICOM), with each dose administered in
      the fasted state. Approximately 18 subjects will be enrolled and randomized to one of 6
      different treatment sequences. There will be a screening visit within 30 days prior to the
      first dose of study drug and a follow up visit within 7-14 days after the last dose. There
      will be a 7 day washout between doses in each treatment period.

      The following PK parameters for DTG, ABC and 3TC will be measured: area under the
      concentration curve from time zero (pre-dose) extrapolated to infinite time
      (AUC(0-infinity)), Area under the concentration-time curve from time zero (pre-dose) to the
      time of the last quantifiable concentration (AUC (0-t)), maximum observed concentration
      (Cmax), lag time before observation of drug concentrations (tlag), time of occurrence of Cmax
      (tmax), terminal phase half-life (t½), apparent clearance following oral dosing (CL/F) and
      apparent terminal phase volume of distribution (Vz/F).
    

Detailed description: 
      Official Title - Randomized, Open-Label, Single Dose, 3 Period, Crossover Evaluation of the
      Relative Bioavailability of Two Experimental Fixed-Dose Combination Tablet Formulations of
      Dolutegravir 50 mg/Abacavir 600 mg/Lamivudine 300 mg Compared to Co administered Dolutegravir
      50 mg and EPZICOM™ (Abacavir 600 mg/Lamivudine 300 mg) Tablets in Healthy Adult Subjects.

      ViiV Healthcare is the new sponsor of this study, and GlaxoSmithKline is in the process of
      updating systems to reflect the change in sponsorship
    

Intervention name(s): Dolutegravir 50 mg/abacavir 600 mg/lamivudine 300 mg; Dolutegravir 50 mg; abacavir 600 mg/lamivudine 300 mg
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Dolutegravir 50 mg/abacavir 600 mg/lamivudine 300 mg is an experimental fixed dose combination tablet of an experimental integrase inhibitor (dolutegravir) and two FDA approved nucleoside reverse transcriptase inhibitors (abacavir and lamivudine); Dolutegravir is an experimental drug in the integrase inhibitor class that is being studied for the treatment of HIV infection.; This is an FDA approved fixed dose combination tablet of two nucleoside reverse transcriptase inhibitors
Other intervention name(s): KIVEXA. This is a trademark of ViiV Healthcare; EPZICOM. This is a trademark of ViiV Healthcare.
Intervention MeSH terms: Lamivudine; Abacavir; Dideoxynucleosides; Dolutegravir
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Keywords: Bioavailability; Lamivudine; Dolutegravir; integrase; Abacavir