MOPE029 - Poster Exhibition
Bioequivalence of darunavir (800mg) co-administered with cobicistat (150mg) as either a fixed-dose combination tablet or as single agents under fasted and fed conditions in healthy volunteers
T.N. Kakuda1, T. van de Casteele2, R. Petrovic2, M. Opsomer2, F. Tomaka1, J. Mrus3, R.M.W. Hoetelmans1
1Janssen Research & Development LLC, Titusville, United States, 2Janssen Infectious Diseases BVBA, Beerse, Belgium, 3Janssen Global Services, Titusville, United States
Background: The investigational booster cobicistat is an alternative to low-dose ritonavir. Comparable darunavir pharmacokinetics were demonstrated for darunavir/cobicistat (800/150mg) as single agents (Mathias et al. IWCPHIV 2010;abstract 28) or as a fixed-dose combination (FDC) (Kakuda et al. IWCPHIV 2012;abstract O20) versus darunavir/ritonavir (800/100mg). We evaluated the bioequivalence of a darunavir/cobicistat FDC versus darunavir/cobicistat co-administered as single agents.
Methods: TMC114IFD1003 (NCT01619527) was a phase I, open-label, 3-panel, randomized, crossover, healthy-volunteer study. Treatments were: 800mg darunavir/150mg cobicistat FDC versus darunavir (2x400mg tablets) and cobicistat (150mg tablet) under fasted (panel 1) or fed (standard breakfast; panel 2) conditions; and FDC under fasted versus fed (high-fat breakfast) conditions (panel 3). Treatments were administered as a single dose with a ≥7-day washout period. Darunavir and cobicistat plasma concentrations were evaluated over 72 hours. Safety assessments were conducted until 7-10 days after last intake.
Results: Most volunteers were white (95-100%) and male (54-58%). Median age (43-46 years) and BMI (25.1-25.3kg/m2) were similar across panels. For darunavir and cobicistat, Cmax and AUC∞ were bioequivalent between the FDC versus single agents, under fasted and fed conditions; 90% CIs were all within 80.00-125.00% (Table). Darunavir Cmax and AUC∞ were significantly higher and tmax was longer following FDC administration under fed versus fasted conditions, whereas cobicistat Cmax and AUC∞ were comparable (although tmax was prolonged with food). Sixty-four (48%) volunteers had ≥1 adverse event (AE) (all grade 1/2). There were no serious AEs, discontinuations due to AEs or clinically relevant differences in AEs/laboratory parameters between groups.
Conclusion: The 800mg darunavir/150mg cobicistat FDC was bioequivalent to darunavir and cobicistat administered as single agents under fasted and fed conditions. Food increased darunavir but not cobicistat exposure; therefore, darunavir/cobicistat should be administered with food. Darunavir/cobicistat were generally well tolerated irrespective of administration method.
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