Abstract CT204: The pharmacokinetics and safety of idelalisib in subjects with severe renal impairment

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Background: Idelalisib (IDELA) is a novel, potent inhibitor of PI3Kδ, which has been shown to be prominently expressed in cells of hematopoietic origin. Renal elimination plays a minor role on elimination of IDELA in humans (∼ 15% of dose excreted in urine). The objective of the present study was to evaluate the PK and safety of IDELA and GS-563117 (primary metabolite) in subjects with severe renal impairment (RI) following a single oral dose of IDELA. Methods: Subjects with severe RI (eGFR 15 - 29 ml/min) and healthy matched controls (eGFR ≥ 80 ml/min) received IDELA 150 mg single dose. Blood and urine samples were collected over 6 days and IDELA/GS-563117 levels were measured using a validated LC/MS/MS method. Geometric least-squares mean ratio and 90% confidence interval of PK exposure parameters in the RI group versus matched controls were calculated, with clinically relevant exposure change defined as ≥ two-fold increase. Safety assessments were performed throughout the study. Results: A total of 12 subjects were enrolled in the study. The majority of subjects were female, white, and of non-Hispanic/Latino ethnicity, and the median age was similar between the 2 groups. Study treatments were generally well tolerated. All AEs were Grade 1 in severity. No clinically significant abnormal changes were observed in vital signs and ECG results from baseline. The AUClast, AUCinf, and Cmax geometric least-squares mean ratio were 127%, 127%, and 105% for IDELA and 124%, 124%, and 96% for GS-563117, respectively, for subjects with severe renal impairment vs matched control subjects (Table 1). There were no relevant relationships between IDELA or GS-563117 exposures and baseline eGFR. Conclusion: There were no clinically relevant differences in the PK of IDELA or GS-563117 between subjects with severe RI vs matched healthy control subjects following a single oral dose of IDELA 150 mg. Dose adjustments for IDELA are not considered necessary in subjects with mild, moderate, or severe renal impairment. View this table: Tmax and T1/2 expressed as median (Q1, Q3) Citation Format: Feng Jin, Michelle Robeson, Huafeng Zhou, Grace Hisoire, Srini Ramanathan. The pharmacokinetics and safety of idelalisib in subjects with severe renal impairment. [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 CT204. doi:10.1158/1538-7445.AM2014-CT204