Effect of food on the pharmacokinetics of nilotinib in chronic myeloid leukemia: assessment of a tailored dose reduction (NiFo-study)

Chronic myeloid leukemia (CML) is a rare disease, but prevalence is rising due
to the effectiveness of treatment with tyrosine kinase inhibitors (TKI) like
nilotinib. The acquisition price of nilotinib (600 mg) is ¤103 per day (¤37.600
per year). The complexity of its dosing regimen (twice daily, fasted,
approximately 12 hours apart) is a factor substantially contributing to
non-adherence, which is directly linked to therapeutic failure. As food
increases nilotinib bioavailability, intake of nilotinib with medium fat Dutch
food is expected to increase the bioavailability to an extent that it will
allow a reduction of the daily dose by about 30 percent. This both reduces
costs substantially and allows for increased adherence simultaneously.

To evaluate the effect of real-life food consumption on the pharmacokinetics of
nilotinib in CML patients

An intervention study with a pre-test post-test design, in patients with
chronic phase CML using nilotinib at a dose of 300 mg bid

Nilotinib at a lowered dose of 200 mg bid, administered with a meal for a
period of seven days. Patients will be instructed about their meals.

Nilotinib concentrations will be measured by means of the DBS sampling method.
Sampling will take place on day 1 and 4 during the fasting phase and day 1, 4
and 7 during the non-fasting phase. Patients are asked to complete a patient
diary collecting data on the exact time of intake of nilotinib, exact time of
blood sampling, consumption of food and side effects. The health status of
patients will be determined prior to study entry from medical history and
electrocardiograms. Online Holter monitoring with emphasis on conduction times
will be performed in all patients.