Pharmacokinetics and safety of niraparib in patients with moderate hepatic impairment.


Journal

Cancer chemotherapy and pharmacology
ISSN: 1432-0843
Titre abrégé: Cancer Chemother Pharmacol
Pays: Germany
ID NLM: 7806519

Informations de publication

Date de publication:
11 2021
Historique:
received: 25 03 2021
accepted: 24 06 2021
pubmed: 30 7 2021
medline: 4 1 2022
entrez: 29 7 2021
Statut: ppublish

Résumé

The purpose of this study is to characterize niraparib pharmacokinetics (PK) and safety in patients with normal hepatic function (NHF) versus moderate hepatic impairment (MHI). Patients with advanced solid tumors were stratified by NHF or MHI (National Cancer Institute-Organ Dysfunction Working Group criteria [bilirubin > 1.5-3 × upper limit of normal and any aspartate aminotransferase elevation]). In the PK phase, all patients received one 300 mg dose of niraparib. In the extension phase, patients with MHI received niraparib 200 mg daily; patients with NHF received 200 or 300 mg based on weight (< 77 kg, ≥ 77 kg)/platelets (< 150,000/µL, ≥ 150,000/µL). PK parameters included maximum concentration (C In the PK phase (NHF, n = 9; MHI, n = 8), mean niraparib C These findings support adjusting the 300 mg niraparib starting dose to 200 mg QD in patients with MHI. NCT03359850; registered December 2, 2017.

Identifiants

pubmed: 34324028
doi: 10.1007/s00280-021-04329-8
pii: 10.1007/s00280-021-04329-8
pmc: PMC8484145
doi:

Substances chimiques

Indazoles 0
Piperidines 0
niraparib HMC2H89N35

Banques de données

ClinicalTrials.gov
['NCT03359850']

Types de publication

Clinical Trial, Phase I Journal Article Multicenter Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

825-836

Subventions

Organisme : NCATS NIH HHS
ID : UL1 TR003167
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States

Informations de copyright

© 2021. The Author(s).

Références

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Auteurs

Mehmet Akce (M)

Winship Cancer Institute of Emory University, Atlanta, GA, USA.

Anthony El-Khoueiry (A)

University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA.

Sarina A Piha-Paul (SA)

University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Emeline Bacque (E)

GlaxoSmithKline, Waltham, MA, USA.

Peng Pan (P)

GlaxoSmithKline, Waltham, MA, USA.
EQRx, Cambridge, MA, USA.

Zhi-Yi Zhang (ZY)

GlaxoSmithKline, Waltham, MA, USA.
Dyne Therapeutics, Waltham, MA, USA.

Reginald Ewesuedo (R)

GlaxoSmithKline, Waltham, MA, USA.

Divya Gupta (D)

GlaxoSmithKline, Waltham, MA, USA.

Yongqiang Tang (Y)

GlaxoSmithKline, Waltham, MA, USA.

Ashley Milton (A)

GlaxoSmithKline, Waltham, MA, USA.
Mersana Therapeutics, Cambridge, MA, USA.

Stefan Zajic (S)

GlaxoSmithKline, Upper Providence, PA, USA.

Patricia L Judson (PL)

GlaxoSmithKline, Waltham, MA, USA.

Cindy L O'Bryant (CL)

University of Colorado Cancer Center, Mail Stop C238, 12850 East Montview Blvd., V20-1223, Aurora, CO, 80045, USA. cindy.obryant@cuanschutz.edu.

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Classifications MeSH