Table 4.
Summary of PK Parameters of Molibresib, Its Two Active Metabolites (GSK3529246), and Total Active Moiety—Itraconazole Interaction (Part 1)
| Analyte | Cohort | Parameter | Molibresib 10 mg Alone | Molibresib 5 mg + Itraconazole |
|---|---|---|---|---|
| Molibresib |
Cohort 1 n = 6 |
Cmax (ng/mL) | 167 (27) | 124 (10) |
| AUC0‐∞ (ng·h/mL) | 672 (11) | 1330 (11) | ||
| Tmax (h) | 0.52 (0.52‐1.5) | 1.5 (0.52‐3.0) | ||
| t1/2 (h) | 7.7 (16) | 10.2 (18) | ||
|
Cohort 2 n = 7 |
Cmax (ng/mL) | 176 (27) | 161 (25) | |
| AUC0‐∞ (ng·h/mL) | 683 (38) | 1470 (14) | ||
| Tmax (h) | 0.52 (0.50‐0.58) | 0.52 (0.27‐0.53) | ||
| t1/2 (h) | 6.6 (42) | 12.5 (18) | ||
|
Overall n = 13 |
Cmax (ng/mL) | 172 (26) | 142 (23) | |
| AUC0‐∞ (ng·h/mL) | 678 (27) | 1410 (13) | ||
| Tmax (h) | 0.52 (0.50‐1.5) | 0.52 (0.27‐3.0) | ||
| t1/2 (h) | 7.07 (32) | 11.4 (20) | ||
| Molibresib 2 active metabolites (GSK3529246) |
Cohort 1 n = 6 |
Cmax (ng/mL) | 44.1 (10) | 2.65 (18) |
| AUC0‐∞ (ng·h/mL) | 492 (13) | 68.2 (33) | ||
| Tmax (h) | 1.5 (0.52‐3.0) | 6.0 (1.5‐8.0) | ||
| t1/2 (h) | 11.2 (18) | 13.7 (31) | ||
|
Cohort 2 n = 7 |
Cmax (ng/mL) | 43.8 (14) | 2.92 (21) | |
| AUC0‐∞ (ng·h/mL) | 551 (15) | 83.4 (20) | ||
| Tmax (h) | 1.5 (1.0‐4.0) | 8.0 (4.0‐8.1) | ||
| t1/2 (h) | 10.7 (25) | 16.2 (48) | ||
|
Overall n = 13 |
Cmax (ng/mL) | 43.9 (12) | 2.80 (20) | |
| AUC0‐∞ (ng·h/mL) | 523 (15) | 76.0 (28) | ||
| Tmax (h) | 1.5 (0.52‐4.0) | 8.0 (1.5‐8.1) | ||
| t1/2 (h) | 10.9 (21) | 15.0 (40) | ||
| Total active moiety |
Cohort 1 n = 6 |
Cmax (nmol/mL) | 478 (22) | 297 (9) |
| AUC0‐∞ (nmol·h/mL) | 2850 (9) | 3310 (12) | ||
| Tmax (h) | 0.52 (0.52‐1.5) | 1.5 (0.52‐3.0) | ||
| t1/2 (h) | 10.7 (27) | 10.0 (20) | ||
|
Cohort 2 n = 7 |
Cmax (nmol/mL) | 494 (24) | 382 (25) | |
| AUC0‐∞ (nmol·h/mL) | 3040 (25) | 3680 (13) | ||
| Tmax (h) | 0.52 (0.50‐0.58) | 0.52 (0.27‐0.53) | ||
| t1/2 (h) | 9.6 (26) | 11.7 (19) | ||
|
Overall n = 13 |
Cmax (nmol/mL) | 486 (23) | 340 (23) | |
| AUC0‐∞ (nmol·h/mL) | 2950 (19) | 3510 (13) | ||
| Tmax (h) | 0.52 (0.50‐1.5) | 0.52 (0.27‐3.0) | ||
| t1/2 (h) | 10.1 (26) | 10.9 (20) |
Cmax, maximum concentration; AUC0‐∞, area under the curve from 0 to infinity; tmax, time of occurrence of Cmax; t1/2, terminal phase elimination half‐life.
Cmax, AUC, and t1/2 are presented as geometric means (CVb%) with 3 significant digits for the geometric mean and 2 for the CVb%; Tmax is presented as median (range) with 2 significant digits.
GSK3529246 represents the sum of GSK3529246 and GSK3536835; GSK3536835 was converted to GSK3529246 prior to analysis. The total active moiety represents the sum of molibresib and its 2 active metabolites reported as GSK3529246.