title: Bioequivalence of a dolutegravir, abacavir, and lamivudine fixed-dose combination tablet and the effect of food.
abstract: BACKGROUND
  The integrase inhibitor dolutegravir and nucleoside analogues abacavir and lamivudine are once-daily treatment options for HIV. This study (NCT01622790) evaluated, first, the bioequivalence (BE) of a fixed-dose combination (FDC) tablet containing dolutegravir 50 mg, abacavir 600 mg, and lamivudine 300 mg (dolutegravir/abacavir/lamivudine FDC) vs coadministered dolutegravir 50 mg and abacavir/lamivudine combination tablets (Epzicom) and, second, the effect of food on the dolutegravir/abacavir/lamivudine FDC tablet.
  
  
  METHODS
  Study part A (66 healthy subjects) was a single-dose, open-label, randomized, 2-period crossover study to evaluate the BE of the dolutegravir/abacavir/lamivudine FDC tablet and dolutegravir + abacavir/lamivudine tablets in the fasted state. In study part B, 12 subjects from part A received the dolutegravir/abacavir/lamivudine FDC tablet with a high-fat meal. BE and food effect were assessed by analysis of variance to determine the ratio of geometric least squares means and associated 90% confidence intervals for key pharmacokinetic parameters for each of dolutegravir, abacavir, and lamivudine.
  
  
  RESULTS
  Sixty-two subjects completed part A. The dolutegravir/abacavir/lamivudine tablet was bioequivalent to the dolutegravir + abacavir/lamivudine tablets; 90% confidence intervals for the geometric least squares mean ratios fell within the 0.8-1.25 BE criteria. The effect of food on the dolutegravir/abacavir/lamivudine FDC tablet was similar to previous food effects observed with the separate formulations. The safety profile was comparable between treatments, with no observed serious or grade 3/4 adverse events.
  
  
  CONCLUSIONS
  The BE of the dolutegravir/abacavir/lamivudine FDC tablet was demonstrated; it may be administered without regard to meals.
authors.affiliation: *GlaxoSmithKline, Research Triangle Park, NC; and †GlaxoSmithKline, Collegeville, PA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Weller
authors.forename: Shuguang
authors.initials: S
authors.lastname: Chen
authors.forename: Julie
authors.initials: J
authors.lastname: Borland
authors.forename: Paul
authors.initials: P
authors.lastname: Savina
authors.forename: Brian
authors.initials: B
authors.lastname: Wynne
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Piscitelli
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004041:Dietary Fats; D004338:Drug Combinations; D005260:Female; D018565:Food-Drug Interactions; D006575:Heterocyclic Compounds, 3-Ring / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D013810:Therapeutic Equivalency; D014622:Vaginal Creams, Foams, and Jellies; D055815:Young Adult; D000099227:Abacavir; D000099226:Dolutegravir
chemical_list: D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D004041:Dietary Fats; D004338:Drug Combinations; D006575:Heterocyclic Compounds, 3-Ring; D019259:Lamivudine; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D014622:Vaginal Creams, Foams, and Jellies; D000099227:Abacavir; D000099226:Dolutegravir