PII-081

F. Jin,1 S. Sharma,1 H. Zhou,2 Y. Gao,3 X. Li,4 T. Newcomb,4 S. Ramanathan1; 1Gilead Sciences, Foster City, CA, 2Cell Therapeutics Inc, Seattle, WA, 3Quantitative Solutions, Menlo Park, CA, 4Gilead Sciences, Seattle, WA

Background: Zydelig™ (idelalisib) is the first PI3Kδ inhibitor approved for the treatment of indolent non-Hodgkin lymphoma (iNHL) and chronic lymphocytic leukemia (CLL). As acid-reducing agents (ARA) are commonly used in these patients, the objective of this analysis was to evaluate the effect of ARA on the pharmacokinetics (PK) of idelalisib.
Methods: Individual idelalisib exposure in iNHL and CLL patients was determined using a Bayesian posthoc procedure from a previously developed population PK model for idelalisib. Idelalisib PK was compared between subjects with or without co-use of ARA (histamine 2 receptor antagonist [H2RA], proton pump inhibitor [PPI], or antacids) based on the ratio and 90% confidence intervals of the geometric means (use vs no use). Subjects were counted as being on ARA if concomitant use of such agents coincided with idelalisib PK sampling ≥50% of the time based on subject-reported data.
Results: The model predicted idelalisib exposures (AUC0-24h, Cmax, and Ctrough) following 150 mg BID dosing were comparable regardless of ARA use (H2RA or PPI, or combined) in both the iNHL and CLL populations, as shown in Table 1.
Conclusion: Acid-reducing agents do not impact idelalisib plasma exposures upon coadministration.
Effect of Histamine 2 Receptor Antagonist (H2RA) or Proton Pump Inhibitors (PPI) Usage on Idelalisib
PK Parameters (Mean (%CV))iNHLCLL
With H2RA
(N = 6)
Without H2RA
(N = 117)
%GLS Means Ratio (90% CI)With H2RA
(N = 16)
Without H2RA
(N = 86)
%GLS Means Ratio (90% CI)
AUC0-24h (ng*h/mL)23400 (21)20800 (35)117 (92, 147)20800 (40)22200 (40)93 (78, 111)
Ctrough (ng/mL)392 (40)338 (62)127 (85, 190)383 (57)388 (72)104 (76, 142)
Cmax (ng/mL)2200 (19)1940 (31)118 (93, 149)1810 (45)2020 (36)86 (71, 104)
With PPIs
(N = 27)
Without PPIs
(N = 95)
With PPIs
(N = 37)
Without PPIs
(N = 64)
AUC0-24h (ng*h/mL)20500 (30)20600 (31)100 (89, 113)21000 (36)22400 (42)95 (84, 109)
Ctrough (ng/mL)323 (47)332 (52)101 (83, 124)390 (60)390 (74)101 (80, 127)
Cmax (ng/mL)1890 (30)1950 (30)98 (86, 111)1780 (34)2090 (38)86 (75, 100)