Abstract CT217: Pharmacokinetics and safety of idelalisib, a novel PI3Kδ inhibitor, in Japanese and Caucasian subjects
Authors: Jin Feng , Robeson Michelle , Zhou Huafeng , Moyer Candra , Ramanathan Srini 
Published: May 2015

Background: PI3K-delta is critical for activation, proliferation and survival of B cells and plays a role in homing and retention in lymphoid tissues. PI3Kδ signaling is hyperactive in many B-cell malignancies. Idelalisib (IDELA) currently in Phase 3 clinical development, is a first-in-class, selective, oral inhibitor of PI3Kδ. The objective of the present study was to evaluate the PK and safety of IDELA and GS-563117 (primary metabolite) in healthy Japanese and Caucasian subjects following IDELA administration to support clinical development in cancer patients in Japan.

Methods: Healthy Caucasian and first-generation descent Japanese subjects (N = 10/group) were enrolled at a single center in the US and administered a single dose of IDELA (150 mg) under fed condition. Blood samples were collected and IDELA and GS-563117 levels were measured using a validated LC/MS/MS method. Safety assessments were performed throughout the study.

Results: All 20 subjects completed the study. Study treatments were generally well tolerated. All treatment-emergent AE and laboratory abnormalities were Grade 1 or 2 in severity. The exposures (AUCinf, AUClast, and Cmax) of IDELA and GS-563117 were slightly higher in Japanese subjects compared with Caucasian subjects (Table 1), and median t1/2 values were comparable. Overall, the observed exposures were in the range of those observed in other IDELA Phase 1 studies with non-Japanese subjects and the differences between Japanese and Caucasian subjects are not considered clinically relevant.

Conclusion: There were no clinically relevant differences in the PK of IDELA and GS-563117 between Japanese and Caucasian subjects following a single oral dose of IDELA 150 mg. No dose adjustment is needed for IDELA 150 mg treatment in Japanese subjects. Single oral doses of IDELA 150 mg were well tolerated in Japanese and Caucasian subjects.

IDELA/GS-563117 PK Parameters in Healthy Japanese vs Caucasian SubjectsPK ParameterMean (%CV)% Geometric Least Squares Means Ratio(90% CI)Japanese(N = 10)Caucasian(N = 10)IDELACmax (ng/mL)2540 (32)1950 (23)128 (104, 157)Tmax (h)1.25 (1.00, 2.50)2.75 (1.50, 3.00)t1/2 (h)8.42 (5.63, 10.6)10.0 (5.32, 17.4)AUClast (ng·h/mL)9670 (27)8190 (38)122 (95.4, 157)AUCinf (ng·h/mL)9830 (27)8320 (38)123 (95.5, 157)GS-563117Cmax (ng/mL)1800 (35)1640 (42)114 (86.0, 152)Tmax (h)2.00 (1.50, 4.00)3.50 (2.50, 4.00)t1/2 (h)8.36 (7.44, 8.80)8.69 (7.68, 9.68)AUClast (ng·h/mL)21900 (56)17700 (62)137 (86.6, 216)AUCinf (ng·h/mL)22400 (56)18200 (62)137 (86.3, 217)Tmax and t1/2: median (Q1, Q3)

Citation Format: Feng Jin, Michelle Robeson, Huafeng Zhou, Candra Moyer, Srini Ramanathan. Pharmacokinetics and safety of idelalisib, a novel PI3Kδ inhibitor, in Japanese and Caucasian subjects. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT217. doi:10.1158/1538-7445.AM2014-CT217