TABLE A4.
Palbo (125 mg PO once daily) Steady-State PK Parameter Summary
| PK Parameter | Study GO39374a | Palbo FDA Clinical Pharmacology Review (NDA 20,7103 review)b,c | ||
|---|---|---|---|---|
| Inavo + Palbo + Letro Arm (n = 22) | Inavo + Palbo + Fulv Arm (n = 20) | Study 1001 (n = 13) | Study 1003 (n = 12) | |
| Geometric mean Cmax, ng/mL (geometric CV%) | 90.7 (60) | — | 94.9 (48) | 116 (28) |
| Median Tmax, hours (range) | 8.0 (0-8) | — | 4.2 (2.0-9.8) | 7.9 (2.2-8.2) |
| Geometric mean AUC0-24, ng × h/mL (geometric CV%) | 1,650 (61) | — | 1,633 (59) | 1,982 (29) |
| Geometric mean Cmin, ng/mL (geometric CV%) | 48.3 (107) | 61.0 (58) | 47.0 (49) | 60.8 (42) |
Abbreviations: AUC0-24, area under the concentration–time curve from 0 to 24 hours after dosing; Cmax, maximum plasma concentration observed; Cmin, minimum plasma concentration observed; CV, coefficient of variation; FDA, US Food and Drug Administration; Fulv, fulvestrant; Inavo, inavolisib; Letro, letrozole; NDA, New Drug Application; Palbo, palbociclib; PK, pharmacokinetics; PO, orally; Tmax, time to maximum concentration.
Commercial freebase formulation of Palbo administered with a meal.
Isethionate capsule formulation of Palbo administered after an overnight fast.
Commercial freebase formulation administered with food has comparable exposure as the isethionate salt formulation on the basis of historical single-agent data of Palbo (NDA 20,7103 review).