The class
A reformulated version of the CETP inhibitor DRL-17822 reduces its food-driven exposure spike (Clin Pharmacol Drug Dev 2019)
Original title: Effect of Food on the Pharmacokinetics of 2 Formulations of DRL-17822, a Novel Selective Cholesteryl Ester Transfer Protein (CETP) Inhibitor, in Healthy Males
DRL-17822, a novel selective CETP inhibitor, showed a more than twentyfold increase in maximum concentration and exposure following a high-fat breakfast with its original nanocrystal formulation, prompting development of an amorphous solid dispersion formulation to reduce this food effect. In a two-part, randomised, open-label, four-way crossover study, 12 healthy men aged 18 to 45 received both formulations fasted and fed, with a low-fat breakfast in part one and a high-fat breakfast in part two. The amorphous solid dispersion formulation substantially increased fasted-state exposure compared with the nanocrystal formulation, but after a high-fat breakfast its exposure increase was smaller (P less than .001), and it produced a more pronounced HDL cholesterol rise in the fasted state, indicating the reformulation gives DRL-17822 a more predictable food-effect profile.
Original abstract
DRL-17822 is a novel selective cholesteryl ester transfer protein inhibitor that showed an increased exposure, including an increase of >20-fold of maximum concentration and area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration, following a high-fat breakfast using a nanocrystal formulation. To reduce this effect of food, we generated an amorphous solid dispersion formulation. In this study, we compared the food effect of both formulations of DRL-17822 in a 2-part randomized, open-label, 4-way crossover study involving healthy adult males 18-45 years of age. In both parts of the study, 12 subjects received both formulations of DRL-17822 in both the fasted and fed states; a low-fat breakfast was provided in the first part and a high-fat breakfast in the second part. Compared to the nanocrystal formulation, the amorphous solid dispersion formulation substantially increased DRL-17822 exposure in the fasted state, including increased maximum concentration, area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration, and area under plasma concentration-time curve from time zero to infinity. Following a high-fat breakfast, DRL-17822 exposure was increased to a lesser extent in the amorphous solid dispersion formulation compared to the nanocrystal formulation (P < .001). Moreover, compared to the nanocrystal formulation the amorphous solid dispersion formulation caused a more pronounced increase in high-density lipoprotein in the fasted state. Consuming breakfast increased the effect of DRL-17822 on high-density lipoprotein. Taken together, our results indicate that by improving its formulation, DRL-17822 has a favorable exposure profile and therefore a more predictable food effect profile.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.