Phase 1 study to evaluate the effects of rifampin on pharmacokinetics of pevonedistat, a NEDD8-activating enzyme inhibitor in patients with advanced solid tumors.
Autor: | Zhou X; Takeda Development Center Americas, Inc. (TDCA), Lexington, MA, USA. xiaofei.zhou@takeda.com., Vaishampayan U; Karmanos Cancer Institute, Detroit, MI, USA.; University of Michigan, Ann Arbor, MI, USA., Mahalingam D; Northwestern Medical Group, Chicago, IL, USA., Harvey RD; Emory University, Atlanta, GA, USA., Chung KY; Prisma Health Cancer Institute/ITOR, Greenville, SC, USA., Sedarati F; Takeda Development Center Americas, Inc. (TDCA), Lexington, MA, USA., Dong C; Takeda Development Center Americas, Inc. (TDCA), Lexington, MA, USA., Faller DV; Takeda Development Center Americas, Inc. (TDCA), Lexington, MA, USA., Venkatakrishnan K; Takeda Development Center Americas, Inc. (TDCA), Lexington, MA, USA.; EMD Serono Research & Development Institute, Inc., MB, Billerica, USA., Gupta N; Takeda Development Center Americas, Inc. (TDCA), Lexington, MA, USA. |
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Jazyk: | angličtina |
Zdroj: | Investigational new drugs [Invest New Drugs] 2022 Oct; Vol. 40 (5), pp. 1042-1050. Date of Electronic Publication: 2022 Aug 06. |
DOI: | 10.1007/s10637-022-01286-8 |
Abstrakt: | Pevonedistat (TAK-924/MLN4924) is an investigational small molecule inhibitor of the NEDD8-activating enzyme that has demonstrated clinical activity across solid tumors and hematological malignancies. Here we report the results of a phase 1 study evaluating the effect of rifampin, a strong CYP3A inducer, on the pharmacokinetics (PK) of pevonedistat in patients with advanced solid tumors (NCT03486314). Patients received a single 50 mg/m 2 pevonedistat dose via a 1-h infusion on Days 1 (in the absence of rifampin) and 10 (in the presence of rifampin), and daily oral dosing of rifampin 600 mg on Days 3-11. Twenty patients were enrolled and were evaluable for PK and safety. Following a single dose of pevonedistat at 50 mg/m 2 , the mean terminal half-life of pevonedistat was 5.7 and 7.4 h in the presence and in the absence of rifampin, respectively. The geometric mean AUC (© 2022. The Author(s).) |
Databáze: | MEDLINE |
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