Food‐effect study of nilotinib in chronic myeloid leukaemia (NiFo study): Enabling dose reduction and relief of treatment burden

Objectives Taking advantage of its food‐dependent bioavailability, the present study investigated the effect of a reduced dose taken with real‐life meals on the pharmacokinetics (PK) of nilotinib in chronic myeloid leukaemia (CML) patients. Methods Nilotinib was taken fasted (300 mg BID, days 1‐4) or with real‐life meals (200 mg BID, days 5‐11). Rich sampling (days 1, 3, 8, 11) allowed for non‐compartmental PK analysis. Nilotinib exposure (AUC0–12 h ‐Cmin ‐Cmax) and its intra‐ and interpatient variability were compared between the two regimens. Adverse events were recorded by means of a patient diary and ECG monitoring. Results Fifteen patients aged 40‐74 years participated. Nilotinib PK following 200 mg BID taken with a meal strongly resembled that of 300 mg BID taken fasted (Cmin percentile (P)10‐P90: 665‐1404 ng/mL and 557‐1743 ng/mL, respectively). Meals delayed nilotinib absorption. Intra‐ and interpatient variability were not increased by intake with meals. Nilotinib with food was well tolerated. Conclusion With support of therapeutic drug monitoring, the use of a reduced 200 mg nilotinib dose with real‐life meals seems feasible and safe. Future (confirmatory) studies should further explore the usefulness of nilotinib dosing together with food, including the relationship with treatment efficacy as well as long‐term effects on quality of life. Clinical Trial Registration: NTR5000 (Netherlands Trial Register, www.trialregister.nl ).