Example 2
Twenty-eight (28) healthy, adult male and female (non-childbearing potential) subjects were enrolled in the study in total; 14 subjects in each study part (Parts 1 and 2). A minimum of 8 female subjects were enrolled in the study (i.e., a minimum of 4 female subjects per study part). Each subject participated in either Part 1 or Part 2, but not both.
Part 1
On Day 1 of Treatment Period 1, a single oral dose of 20 mg mitapivat sulfate was administered. Serial blood samples for plasma assay of mitapivat concentrations and its CYP3A4 metabolite, referred to herein as the “Metabolite” (structure below),
In Treatment Period 1, mitapivat sulfate was administered orally with approximately 240 mL of water. In Treatment Period 2, on Days 1 to 4, itraconazole was administered alone immediately followed by approximately 220 mL of water, and on Day 5, itraconazole was administered first (no water) and was immediately followed by mitapivat sulfate administration with approximately 220 mL of water. Study drugs (mitapivat sulfate and itraconazole) were administered following an overnight fast of at least 10 hours on Day 1 of Treatment Period 1 (mitapivat sulfate only) and Day 5 of Treatment Period 2 (mitapivat sulfate and itraconazole), and subjects remained fasted for 4 hours after dosing. On all other dosing days, itraconazole was administered following a predose fast of at least 4 hours and subjects remained fasted for at least 2 hours after dosing.
Part 2
On Day 1 of Treatment Period 1, a single oral dose of 50 mg mitapivat sulfate was administered. Serial blood samples for plasma assay of mitapivat and the Metabolite concentrations were collected from predose to 120 hours following administration of mitapivat sulfate. In Treatment Period 2, an oral dose of 600 mg rifampin was administered QD for 12 consecutive days (Day 1 through Day 12 of Treatment Period 2) with a single oral dose of 50 mg mitapivat sulfate coadministered on Day 8. Serial blood samples for plasma assay of mitapivat sulfate and the Metabolite concentrations were collected from predose to 120 hours following coadministration of mitapivat and rifampin on Day 8.
In Part 2, study drugs were administered with approximately 240 mL of water on all dosing days including the coadministration of mitapivat sulfate and rifampin on Day 8 of Treatment Period 2. Mitapivat sulfate and rifampin was administered following an overnight fast of at least 10 hours on Day 1 of Treatment Period 1 (mitapivat sulfate only) and Day 8 of Treatment Period 2 (both mitapivat sulfate and rifampin) and subjects remained fasted for 4 hours after dosing. On all other dosing days, rifampin was administered following a predose fast of at least 4 hours and subjects remained fasted for at least 2 hours after dosing. There was a washout period of 7 days between the mitapivat sulfate dose in Treatment Period 1 and the first itraconazole (Part 1) or rifampin (Part 2) dose in Treatment Period 2. All study drugs were consumed within 5 minutes for both Part 1 and Part 2.
