Table 2.
Geometric mean ratios and 90% confidence intervals (CIs) for comparison of oral capsule and intravenous (i.v.) formulation of ibrutinib, with and without food (treatment B vs. treatment A), and with and without grapefruit juice (treatment C vs. treatment B)
| Parameter* | Test treatment/reference treatment | N | Geometric mean | Ratio: test/reference (%) | 90% CI (%) | Intraparticipant CV (%) |
|---|---|---|---|---|---|---|
| Oral (treatment B vs. treatment A: with vs. without food) | ||||||
| Cmax (ng ml–1) | B | 8 | 121 | 352 | (213, 582) | 62 |
| A | 8 | 34 | ||||
| AUClast (ng h ml–1) | B | 8 | 588 | 223 | (167, 297) | 31 |
| A | 8 | 264 | ||||
| AUC∞ (ng h ml–1) | B | 4 | 677 | 187 | (137, 256) | 19 |
| A | 4 | 362 | ||||
| i.v. (treatment B vs. treatment A: with vs. without food | ||||||
| B | 8 | 5032 | 81 | (37, 176) | 99 | |
| Cmax (pg ml–1) | A | 8 | 6255 | |||
| B | 8 | 1380 | 85 | (72, 100) | 18 | |
| AUClast (pg h ml–1) | A | 8 | 1631 | |||
| B | 6 | 1329 | 82 | (68, 100) | 17 | |
| AUC∞ (pg h ml–1) | A | 6 | 1612 | |||
| Oral (treatment C vs. treatment B: with vs. without GFJ) | ||||||
| Cmax (ng ml–1) | C | 8 | 437 | 360 | (269, 483) | 31 |
| B | 8 | 121 | ||||
| AUClast (ng h ml–1) | C | 8 | 1236 | 210 | (182, 243) | 15 |
| B | 8 | 588 | ||||
| AUC∞ (ng h ml–1) | C | 7 | 1378 | 215 | (184, 250) | 14 |
| B | 7 | 643 | ||||
| i.v. (treatment C vs. treatment B: with vs. without GFJ) | ||||||
| Cmax (pg ml–1) | C | 8 | 5903 | 117 | (58, 238) | 84 |
| B | 8 | 5032 | ||||
| AUClast (pg h ml–1) | C | 8 | 1401 | 102 | (89, 116) | 14 |
| B | 8 | 1380 | ||||
| AUC∞ (pg h ml–1) | C | 7 | 1416 | 104 | (90, 120) | 13 |
| B | 7 | 1363 | ||||
AUC∞, area under the plasma concentration–time curve from time zero to infinite time, calculated as the sum of AUClast and Clast/λz; AUClast, area under the plasma concentration–time curve from time zero to the time of the last quantifiable concentration; Cmax, maximum plasma concentration; CV, coefficient of variation.
A mixed‐effects model with treatment as a fixed effect and subject as a random effect was used for analysis on a log scale and the results were presented at original scale after antilogarithmic transformation.