Effect of Food on the Pharmacokinetics of 2 Formulations of DRL-17822, a Novel Selective Cholesteryl Ester Transfer Protein (CETP) Inhibitor, in Healthy Males

Annelieke C Kruithof*, Rajinder Kumar, Jasper Stevens, Marieke L de Kam, Anirudh Gautam, Shanavas Alikunju, Bijay K Padhi, Swati Kulkarni, Rajeev S Raghuvanshi, Rajesh Gandhi, Jacobus Burggraaf, Ingrid M C Kamerling

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

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    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.

    Original languageEnglish
    Pages (from-to)1042-1052
    Number of pages11
    JournalClinical pharmacology in drug development
    Volume8
    Issue number8
    DOIs
    Publication statusE-pub ahead of print - 10-Jun-2019

    Keywords

    • amorphous solid dispersion formulation
    • cholesteryl ester transfer protein (CETP) inhibition
    • DRL-17822
    • food effect
    • nanocrystal formulation
    • pharmacokinetics

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