TABLE 3.
Statistical comparison of primary pharmacokinetic parameters of midazolam, S‐/R‐warfarin, and repaglinide when administered alone or at steady‐state asciminib
| PK parameter | Treatment | n |
Adjusted G mean |
Comparison | Treatment comparison | |
|---|---|---|---|---|---|---|
| G mean ratio | 90% CI | |||||
| Midazolam | ||||||
| AUCinf (ng × h/ml) | Midazolam | 22 | 37.4 | Midazolam + asciminib/midazolam | 1.28 | 1.15–1.43 |
| Midazolam + asciminib | 21 | 48.0 | ||||
| AUClast (ng × h/ml) | Midazolam | 22 | 35.4 | Midazolam + asciminib/midazolam | 1.27 | 1.14–1.41 |
| Midazolam + asciminib | 21 | 44.8 | ||||
| Cmax (ng/ml) | Midazolam | 22 | 15.9 | Midazolam + asciminib/midazolam | 1.11 | 0.96–1.28 |
| Midazolam + asciminib | 21 | 17.6 | ||||
| S‐Warfarin | ||||||
| AUCinf (ng × h/ml) | Warfarin | 21 | 7350 | Warfarin + asciminib/warfarin | 1.41 | 1.37–1.45 |
| Warfarin + asciminib | 20 | 10,300 | ||||
| AUClast (ng ×h/ml) | Warfarin | 21 | 6480 | Warfarin + asciminib/warfarin | 1.39 | 1.36–1.42 |
| Warfarin + asciminib | 21 | 9010 | ||||
| Cmax (ng/ml) | Warfarin | 22 | 209 | Warfarin + asciminib/warfarin | 1.08 | 1.04–1.13 |
| Warfarin + asciminib | 21 | 227 | ||||
| R‐Warfarin | ||||||
| AUCinf (ng ×h/ml) | Warfarin | 18 | 10,800 | Warfarin + asciminib/warfarin | 1.25 | 1.21–1.29 |
| Warfarin + asciminib | 15 | 13,500 | ||||
| AUClast (ng ×h/ml) | Warfarin | 21 | 9700 | Warfarin + asciminib/warfarin | 1.24 | 1.21–1.26 |
| Warfarin + asciminib | 21 | 12,000 | ||||
| Cmax (ng/ml) | Warfarin | 22 | 196 | Warfarin + asciminib/warfarin | 1.10 | 1.04–1.15 |
| Warfarin + asciminib | 21 | 215 | ||||
| Repaglinide | ||||||
| AUCinf (ng ×h/ml) | Repaglinide | 23 | 10,600 | Repaglinide + asciminib/repaglinide | 1.08 | 1.02–1.14 |
| Repaglinide + asciminib | 24 | 11,400 | ||||
| AUClast (ng ×h/ml) | Repaglinide | 25 | 10,300 | Repaglinide + asciminib/repaglinide | 1.09 | 1.03–1.15 |
| Repaglinide + asciminib | 24 | 11,200 | ||||
| Cmax (ng/ml) | Repaglinide | 25 | 6710 | Repaglinide + asciminib/repaglinide | 1.14 | 1.01–1.28 |
| Repaglinide +asciminib | 24 | 7640 | ||||
Results were back‐transformed to obtain the adjusted G mean, G mean ratio, and 90% CI.
AUCinf, area under the plasma concentration–time curve from zero to infinity; AUClast, area under the plasma concentration–time curve from zero to the last quantifiable concentration; CI, confidence interval; Cmax, maximum plasma concentration; G mean, geometric mean; GCV%, geometric coefficient of variation; n, number of observations used for analysis; PK, pharmacokinetic.