Abstract
Purpose
Idelalisib is a novel, potent inhibitor of phosphatidylinositol 3-kinase delta (PI3Kδ), which is prominently expressed in cells of hematopoietic origin. Renal excretion plays a minor role in elimination of idelalisib in humans (~15 % of the dose is excreted in urine). This study evaluated the pharmacokinetics (PK) and safety of idelalisib and GS-563117 (its inactive primary metabolite) in subjects with severe renal impairment and healthy subjects.
Methods
Subjects with severe renal impairment were matched in age, sex, and body mass index with healthy subjects who had normal renal function. Each subject received a single oral dose of idelalisib at 150 mg, and safety assessments and PK analyses were performed.
Results
Compared with healthy subjects, the geometric least-squares mean ratio of area under the concentration–time curve from zero to last PK observation (AUClast), area under the concentration–time curve from zero to infinity (AUCinf), and maximum observed plasma concentration (C max) were 127, 127, and 105 % for idelalisib and 124, 124, and 96 % for GS-563117, respectively, in subjects with severe renal impairment.
Conclusions
There were no clinically relevant changes of idelalisib or GS-563117 PK in subjects with severe renal impairment versus matched healthy controls. No relevant relationships were identified between idelalisib or GS-563117 exposures and baseline creatinine clearance. Idelalisib dosing was generally well tolerated with most treatment-emergent adverse events and laboratory abnormalities assessed as grade 1 or 2 in severity. Accordingly, dose adjustments for idelalisib are not necessary in subjects with mild, moderate, or severe renal impairment.
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Editorial assistance was provided by Impact Communication Partners, Inc. Financial support for this study was provided by Gilead Sciences, Inc.
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This study was sponsored by Gilead Sciences, Inc. All authors are employees of Gilead Sciences, Inc., and may own stock or hold stock options in the company.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
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Jin, F., Robeson, M., Zhou, H. et al. The pharmacokinetics and safety of idelalisib in subjects with severe renal impairment. Cancer Chemother Pharmacol 76, 1133–1141 (2015). https://doi.org/10.1007/s00280-015-2898-1
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DOI: https://doi.org/10.1007/s00280-015-2898-1