Does food affect brigatinib/brigatinib?

The next-generation anaplastic lymphoma kinase (ALK) inhibitor brigatinib/brigatinib has received accelerated approval in the United States for the treatment of patients with metastatic ALK+ non-small cell lung cancer who have progressed or are intolerant to crizotinib. A clinical study was conducted to evaluate the effect of food on the pharmacokinetics (PK) of brigatinib.

In a Phase 2 sequence crossover study, healthy subjects received a single oral dose of brigatinib 180 mg (2 x 90 mg tablets) after a 10-hour fast or a high-fat meal. Plasma samples for pharmacokinetic characterization were collected within 168 hours after dosing. Twenty-four subjects (mean age, 44 years; 58% male) were recruited, 21 of whom were included in the PK-evaluable population. Peak brigatinib concentrations were reduced by 13% under fed (high-fat meal) conditions compared with fasted conditions, with no effect on the area under the concentration-time curve.

The median time to peak brigatinib concentration was longer under fed conditions (5 hours) than under fasted conditions (2 hours). Treatment-emergent adverse events were similar under fasted (48%) and fed (46%) conditions and were of moderate intensity. Consumption of a high-fat meal reduced the oral absorption rate of brigatinib but had no effect on the extent of absorption, thus supporting the administration of brigatinib independent of diet.

When patients received a single oral dose of brigatinib in the dose range 30-240 mg, the average time for the drug to reach maximum plasma concentration was 1 to 4 hours. A high-fat diet does not have a significant impact on brigatinib exposure, meaning patients do not need to consider the fat content of their meals when taking the drug. Therefore, brigatinib can be taken with or without food.