Table 5.
Simcyp Prediction and Actual Observed Effect of Itraconazole on PK Parameters of Molibresib, Its Two Active Metabolites (GSK3529246), and Total Active Moiety—Part 1
| Molibresib | GSK3529246 | Total Active Moiety | |||
|---|---|---|---|---|---|
| Parameter | Observed Geometric Mean Ratio (90%CI) | Predicted Ratio (5th and 95th Percentiles) | Observed Geometric Mean Ratio (90%CI) | Predicted Ratio (5th and 95th Percentiles) | Observed Least‐Squares Mean Ratio (90%CI) |
| Cmax | 1.66 (1.43‐1.92) | 1.30 (1.14‐1.52) | 0.13 (0.11‐0.14) | 0.14 (0.03‐0.55) | 1.40 (1.22‐1.61) |
| AUC | 4.15 (3.77‐4.58) | 4.41 (2.95‐6.02) | 0.29 (0.26‐0.32) | 0.29 (0.09‐0.82) | 2.38 (2.24‐2.52) |
CI, confidence interval; Cmax, maximum concentration; AUC, area under the curve from 0 to infinity.
The predicted ratios are presented as geometric mean and 5th and 95th percentiles for 100 simulated subjects. The total active moiety represents the sum of molibresib and its 2 active metabolites reported as GSK3529246.