A Dose Calibration Study Comparing IkT-001Pro to Imatinib Mesylate 400mg

Part A, Dose Calibration Cohort:

This is a crossover design dose calibration study in healthy volunteers to identify a dose of IkT-001Pro film-coated tablets that would be equivalent to imatinib free base 400 mg film-coated tablets containing imatinib mesylate.

Dose calibration cohorts will each consist of eight (8) subjects who will receive a single dose of IkT-001Pro at 400, 500 or 600 mg and then crossover to a single dose of imatinib 400 mg delivered as imatinib mesylate following a 7-day washout. The three cohorts will have staggered starting points. The 400 mg IkT-001Pro dose, washout and 400 mg imatinib delivered as imatinib mesylate will be completed first including full PK analysis. Following review of the PK data at 400 mg IkT-001Pro, the 500 mg and 600 mg cohorts will be enrolled approximately simultaneously.

Pharmacokinetic plasma samples for all three cohorts will be drawn pre-dose at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours after dosing. A 7-day washout period will take place between dosing of IkT-001Pro and dosing of 400 mg imatinib delivered as imatinib mesylate. PK plasma samples for the imatinib mesylate arm will be obtained on the same sampling schedule as the IkT-001Pro arm.

Part B- Dose Equivalence Cohort:

Part B will test the bioequivalence of the IkT-001Pro dose chosen in Part A. In this two-period crossover design dose equivalence study, up to 16 subjects will receive IkT-001Pro and up to 16 subjects will receive 400 mg imatinib as imatinib mesylate as a single dose. The dose of IkT-001Pro will be computed from the exposures measured in Part A to estimate the dose of IkT-001Pro that should be equivalent to 400 mg imatinib delivered as imatinib mesylate. After a 7-day washout period, the subjects that began on IkT-001Pro will switch to 400 mg imatinib delivered as imatinib mesylate. Similarly, the subjects that began on 400 mg imatinib delivered as imatinib mesylate will switch to the equivalent dose of IkT-001Pro. Blood samples for PK assessment will be drawn pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours after dosing for both IkT-001Pro and 400 mg imatinib.

Part C- Dose Equivalence at 600 mg:

Part C will test the single dose bioequivalence of imatinib free base delivered as the equivalent dose IkT-001Pro dose computed from Part A to single dose of imatinib delivered as 600 mg imatinib mesylate. Up to eight (8) subjects will be administered a single dose of 800 mg IkT-001Pro. After a 7-day washout period, the subjects will switch to 600 mg imatinib free base delivered as imatinib mesylate.