title: A randomized trial in healthy subjects to assess the bioequivalence of an atazanavir/cobicistat fixed-dose combination tablet versus administration as separate agents.
abstract: BACKGROUND
  Cobicistat (COBI) is an alternative pharmacoenhancer to ritonavir. A fixed-dose combination (FDC) tablet containing atazanavir (ATV) and COBI has been developed for the treatment of HIV-1-infected patients.
  
  
  METHODS
  This open-label, single-centre, single-dose, crossover study, randomized 64 healthy subjects to one of eight treatment sequences. Under light meal conditions, maximum plasma concentration (Cmax), area under the plasma concentration-time curve (AUC) to infinity (AUCINF) and AUC to the last measurable concentration (AUC0-T) for ATV and COBI administered as an FDC of ATV/COBI (300/150 mg) were compared to those following administration as separate agents given together; bioequivalence was concluded if the 90% CIs of the geometric mean ratios fell within the predetermined range of 0.80, 1.25. ATV and COBI pharmacokinetic parameters following administration as the FDC or as separate agents were also compared under fasted conditions. The effect of food (light and high-fat meals) on the pharmacokinetics of ATV and COBI for the FDC was also assessed.
  
  
  RESULTS
  ATV and COBI administered in an FDC tablet were bioequivalent to the individual agents when given with a light meal. Under fasted conditions, pharmacokinetic parameters for ATV and COBI were similar for the individual components and the FDC. For the FDC, systemic exposure to ATV increased with a light meal compared to fasted conditions, and ATV concentration 24 h post-dose was similar with a light meal compared with a high-fat meal.
  
  
  CONCLUSIONS
  ATV/COBI (300/150 mg) FDC tablet was bioequivalent to coadministration as separate agents with a light meal in healthy subjects. Clinicaltrials.gov identifier NCT01837719.
authors.affiliation: Research and Development, Bristol-Myers Squibb, Pennington, NJ, USA. heather.sevinsky@bms.com.
authors.forename: Heather
authors.initials: H
authors.lastname: Sevinsky
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Tao
authors.forename: Reena
authors.initials: R
authors.lastname: Wang
authors.forename: Palanikumar
authors.initials: P
authors.lastname: Ravindran
authors.forename: Karen
authors.initials: K
authors.lastname: Sims
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Xu
authors.forename: Navin
authors.initials: N
authors.lastname: Jariwala
authors.forename: Richard
authors.initials: R
authors.lastname: Bertz
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000069446:Atazanavir Sulfate / Q000493:pharmacokinetics*; D001682:Biological Availability; D000069547:Cobicistat / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D065692:Cytochrome P-450 CYP3A Inhibitors / Q000493:pharmacokinetics*; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D065692:Cytochrome P-450 CYP3A Inhibitors; D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D000069446:Atazanavir Sulfate; D000069547:Cobicistat