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

Kruithof, A. C., Kumar, R., Stevens, J., de Kam, M. L., Gautam, A., Alikunju, S., Padhi, B. K., Kulkarni, S., Raghuvanshi, R. S., Gandhi, R., Burggraaf, J. & Kamerling, I. M. C., 10-Jun-2019, In : Clinical pharmacology in drug development. 8, 8, p. 1042-1052 11 p.

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

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DOI

  • 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

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
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

ID: 85444357