The Effect of a High-Fat Meal on the Pharmacokinetics of Brigatinib, an Oral Anaplastic Lymphoma Kinase Inhibitor, in Healthy Volunteers.

Abstract

Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, received accelerated approval in the United States for the treatment of patients with metastatic ALK+ non-small-cell lung cancer who have progressed on or are intolerant to crizotinib. A clinical study was conducted to assess the effect of food on brigatinib pharmacokinetics (PK). Healthy subjects received a single oral dose of brigatinib 180 mg (2 × 90-mg tablets) after a 10-hour fast or after a high-fat meal in a 2-period, 2-sequence crossover study. Plasma samples for PK characterization were collected over 168 hours postdose. Twenty-four subjects were enrolled (mean age 44 years; 58% male), with 21 included in the PK-evaluable population. Brigatinib peak concentration was reduced by 13% under fed (high-fat meal) versus fasted conditions, with no effect on area under the concentration-time curve. The median time to peak concentration of brigatinib was longer under fed conditions (5 hours) than in fasted conditions (2 hours). Treatment-emergent adverse events were similar under fasted (48%) and fed (46%) conditions and were of mild intensity. Consumption of a high-fat meal decreased the rate of brigatinib oral absorption but had no impact on the extent of absorption, thereby supporting brigatinib administration without regard to meals. These recommendations are reflected in the US prescribing information for brigatinib.

• Authors: Meera Tugnait, Neeraj Gupta, Michael J Hanley, Karthik Venkatakrishnan, Daryl Sonnichsen, David Kerstein, David J Dorer, Narayana Narasimhan
• Journal: Clinical pharmacology in drug development (Clin Pharmacol Drug Dev) Vol. 8 Issue 6 Pg. 734-741 (08 2019) ISSN: 2160-7648 [Electronic] United States
• PMID: 30570839 (Publication Type: Clinical Trial, Phase I, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

Chemical References

• Organophosphorus Compounds
• Protein Kinase Inhibitors
• Pyrimidines
• Tablets
• brigatinib

Topics

• Administration, Oral
• Adult
• Biological Availability
• Cross-Over Studies
• Diet, High-Fat (adverse effects)
• Fasting (blood)
• Female
• Food-Drug Interactions
• Healthy Volunteers
• Humans
• Male
• Ontario
• Organophosphorus Compounds (administration & dosage, pharmacokinetics)
• Protein Kinase Inhibitors (administration & dosage, pharmacokinetics)
• Pyrimidines (administration & dosage, pharmacokinetics)
• Tablets
• Young Adult