CML-268: Study to Evaluate the Effect of Fatty Meals on Nilotinib Drug Levels in Patients with CML-CP

Context: Nilotinib is an oral tyrosine kinase inhibitor used in chronic myeloid leukemia (CML) and is known to have food interactions. It is recommended for administration in a fasting state (meals taken either 2 hours after dose or 1 hour before a dose). Food, especially fat-rich food, has been shown to increase the bioavailability of drugs. If the drug is allowed to be taken with food, it will be convenient for patients and also lower the dose needed to produce clinical benefit. This will decrease the cost of therapy and will improve the quality of life of patients. Objective: To assess the effect of fatty meals on nilotinib drug levels in patients with CML. Design/Setting/Patients/Intervention: It is a single-center, open-label, pharmacokinetic study. There were 5 cohorts with 6 patients enrolled in each. A total of 30 patients were included in the study. The patient population included patients of newly diagnosed CML (chronic phase). The dose of nilotinib in each cohort was 150 mg OD, 200 mg OD, 150 mg BD, 200 mg BD, and 300 mg BD, respectively. The drug was given an empty stomach for an initial 8 days, followed by fatty meals for the next 8 days. Fatty meals were defined as 2 slices of bread with 10 grams of butter. Two ml blood was withdrawn at specified time points at 0 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 16 hours, 20 hours, and 24 hours and on day 8 (0 hour and 3 hours). Nilotinib drug levels were estimated by liquid chromatography mass spectrometry. Main Outcome Measures: To assess serum drug levels of nilotinib in both fasting and post-meals statuses to determine an increase in drug levels with fatty meals. Results: Initial results of the study have shown the significant benefit of food on nilotinib drug levels. We will discuss the complete results at the SOHO conference. Acknowledgements: The study is funded by a research grant from the Indian Council of Medical Research, New Delhi (ICMR).