title: Evaluation of food effect on the oral bioavailability of pradigastat, a diacylglycerol acyltransferase 1 inhibitor.
abstract: Pradigastat, a diacylglycerol acyltransferase 1 inhibitor, is being developed for the treatment of familial chylomicronemia syndrome. The results of two studies that evaluated the effect of food on the oral bioavailability of pradigastat using randomized, open-label, parallel group designs in healthy subjects (n=24/treatment/study) are presented. In study 1, a single dose of 20 mg pradigastat was administered under the fasted condition or with a high-fat meal. In study 2, a single dose of 40 mg pradigastat was administered under the fasted condition or with a low- or high-fat meal. At the 20 mg dose, the pradigastat Cmax and AUClast increased by 38% and 41%, respectively, with a high-fat meal. When 40 mg pradigastat was administered with a low-fat meal, the Cmax and AUClast increased by 8% and 18%, respectively, whereas with a high-fat meal the increase was 20% and 18%, respectively. The population pharmacokinetic analysis with the pooled data from 13 studies indicated that administration of pradigastat with a meal resulted in an increase of 30% in both the Cmax and AUC parameters. Based on these results, food overall increased pradigastat exposure in the range of less than 40%, which is not considered clinically significant. Both 20 and 40 mg doses of pradigastat were well tolerated under fasted or fed conditions.
authors.affiliation: Novartis Institutes for BioMedical Research, East Hanover, NJ, USA.
authors.forename: Surya P
authors.initials: SP
authors.lastname: Ayalasomayajula
authors.affiliation: Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Meyers
authors.affiliation: Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.affiliation: Novartis Institutes for BioMedical Research, East Hanover, NJ, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Kagan
authors.affiliation: Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: Matott
authors.affiliation: Novartis Healthcare Pvt. Ltd, Hyderabad, India.
authors.forename: Parasar
authors.initials: P
authors.lastname: Pal
authors.affiliation: Alcon Laboratories Inc., Fort Worth, TX, USA.
authors.forename: Tapan
authors.initials: T
authors.lastname: Majumdar
authors.affiliation: Novartis Institutes for BioMedical Research, Shanghai, China.
authors.forename: Zhenzhong
authors.initials: Z
authors.lastname: Su
authors.affiliation: Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Crissey
authors.affiliation: Novartis Institutes for BioMedical Research, East Hanover, NJ, USA.
authors.forename: Sam
authors.initials: S
authors.lastname: Rebello
authors.affiliation: Novartis Institutes for BioMedical Research, East Hanover, NJ, USA.
authors.forename: Gangadhar
authors.initials: G
authors.lastname: Sunkara
authors.affiliation: Novartis Institutes for BioMedical Research, East Hanover, NJ, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
mesh_terms: D000085:Acetates / Q000008:administration & dosage* / Q000097:blood*; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000631:Aminopyridines / Q000008:administration & dosage* / Q000097:blood*; D001682:Biological Availability; D051048:Diacylglycerol O-Acyltransferase / Q000037:antagonists & inhibitors* / Q000097:blood*; D059305:Diet, High-Fat / Q000379:methods; D004041:Dietary Fats / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000097:blood; D005215:Fasting / Q000378:metabolism; D018565:Food-Drug Interactions / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000085:Acetates; D000631:Aminopyridines; D004041:Dietary Fats; D004791:Enzyme Inhibitors; C000594809:pradigastat; D051048:Diacylglycerol O-Acyltransferase
keywords: bioavailability; food effect; pharmacokinetics; pradigastat