Evaluation of the Bioequivalence of a Combined Formulated Tablet
Condition: 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. Part A of this study will be a single-dose,
      two-treatment crossover pivotal bioequivalence (BE) evaluation of the DTG/ABC/3TC FDC tablet
      in 66 healthy subjects. The reference formulations in this trial will be the 50 mg DTG tablet
      that is currently being used in the Phase 3 clinical trials and the already marketed FDC
      tablet product EPZICOM™ (ABC 600 mg/3TC 300 mg).It is intended that the results of this
      pivotal bioequivalence study will show that the proposed commercial DTG/ABC/3TC FDC tablet
      formulation is bioequivalent to DTG plus EPZICOM administered as separate tablets. Part B of
      this study will evaluate the effect of a high fat meal on the FDC tablet in 12 healthy
      subjects that have already participated in Part A of the study. 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), terminal elimination phase rate constant (λz),
      percentage of AUC obtained by extrapolation (%AUCex),apparent clearance following oral dosing
      (CL/F) and apparent terminal phase volume
    


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)
Primary purpose: Basic Science