Abstract PE10/17
 
A Single Dose Food Effect Study of Raltegravir (RAL) Formulations Print
 
R. Krishna1, M.L. Rizk2, V. Schulz3, B. Ingelse4, P. Larson1
1Merck Sharp & Dohme Corp., Rahway, United States, 2Merck Sharp & Dohme Corp., West Point, United States, 3Merck Sharp & Dohme Corp., North Wales, United States, 4Merck Sharp & Dohme Corp., Oss, Netherlands
 
An open-label, single-dose, randomized, 2-cohort, 3-period, crossover, study assessed the effect of food on the pharmacokinetics (PK) of RAL after a 1200 mg dose. Thirty-six healthy male and female subjects (18 to 55 years) received either a 1200 mg dose of a reformulated (r) tablet of RAL (2 x 600 mg) or the poloxamer (p) tablet of RAL (3 x 400 mg; ISENTRESS). RAL was found to be generally well tolerated in healthy subjects. Administration of a 1200 mg pRAL in the fasted state resulted in a geometric mean (CV%) C24hr of 46.3 nM (54%), Cmax of 9.4 µM (203%), and AUCinf of 34.9 µM-hr (122%). Similarly, administration of a 1200 mg rRAL tablet in the fasted state resulted in a geometric mean (CV%) C24hr of 59.8 nM (87%), Cmax of 23.1 µM (77%), and AUCinf of 58.1 µM-hr (67%). Administration of pRAL with food resulted in a 71% decrease in AUC, 75% decrease in Cmax, and 18% decrease in C24hr (low fat meal); and a 26% increase in AUC, 24% decrease in Cmax, and 70% increase in C24hr (high fat meal). While the low fat meal food effect is directionally similar to those observed with the marketed product, the high fat meal food effect finding is different (a high fat meal increased AUC by 111%, Cmax by 96%, and C12hr by 313% for the marketed 400 mg BID dose). Administration of rRAL with food resulted in a 40% decrease in AUC, 52% decrease in Cmax, and 16% decrease in C24hr (low fat meal); and a 3% increase in AUC, 28% decrease in Cmax, and 12% decrease in C24hr (high fat meal). Multiple dose studies are ongoing, which together with PK/PD modeling and simulation, will further assess the feasibility of a once-daily regimen.


Assigned speakers:
Rajesh Krishna , Merck Sharp & Dohme Corp. , Rahway , United States

Assigned in sessions:
17.10.2013, 12:00-14:00, Poster Session, Poster Session 1, Exhibition
18.10.2013, 12:00-14:00, Poster Session, Poster Session 2, Exhibition