Table 4.
Occupancy of Bruton's tyrosine kinase (BTK) following single and multiple oral doses of PRN1008
| Part A Dose | PRN1008% BTK Occupancy (Mean ± SD)** | |||||||
|---|---|---|---|---|---|---|---|---|
| Day 1 (4 h) | Day 1 (12 h) | Day 1 (24 h) | ||||||
| 50 mg | 18 ± 7.9 | 18 ± 12 | 12 ± 5.5 | |||||
| 150 mg | 55 ± 15 | 33 ± 7.1 | 21 ± 17 | |||||
| 300 mg | 75 ± 7.3 | 61 ± 9.6 | 45 ± 14 | |||||
| 600 mg | 92 ± 3.2 | 79 ± 9.7 | 57 ± 17 | |||||
| 1200 mg | 92 ± 3.0 | 83 ± 6.9 | 63 ± 14 | |||||
| Part B Dose | PRN1008% BTK Occupancy (Mean ± SD)** | |||||||
|---|---|---|---|---|---|---|---|---|
| Day 1 (4 h) | Day 1 (12 h) | Day 1 (24 h) | Day 3 (24 h) | Day 10 (Predose) | Day 10 (4 h^) | Day 10 (12 h) | Day 10 (24 h) | |
| 300 mg QD | 79 ± 7.7 | 57 ± 8.8 | 31 ± 18 | 28 ± 15 | 29 ± 24.6 | 84 ± 4.4 | 62 ± 12.7 | 27 ± 19.4 |
| 300 mg BID | 78 ± 8.6 | 59 ± 18 | 62 ± 18 | 73 ± 12 | 74 ± 4.2 | 91 ± 2.3 | 77 ± 6.7 | 60 ± 8.3 |
| 600 mg QD | 90 ± 5.8 | 78 ± 7.2 | 60 ± 9.9 | 58 ± 13 | 58 ± 11.4 | 93 ± 2.0 | 80 ± 5.6 | 59 ± 11.1 |
| 450 mg BID | 81 ± 7.4 | 73 ± 8.7 | 75 ± 8.9 | 77 ± 7.8 | 76 ± 7.4 | 91 ± 4.6 | 75 ± 8.4 | 54 ± 15.1 |
SD, standard deviation; QD = every 24 h; BID = every 12 h