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dc.contributor.authorVishwanathan, Ken_US
dc.contributor.authorDickinson, PAen_US
dc.contributor.authorBui, Ken_US
dc.contributor.authorCassier, PAen_US
dc.contributor.authorGreystoke, Aen_US
dc.contributor.authorLisbon, Een_US
dc.contributor.authorMoreno, Ven_US
dc.contributor.authorSo, Ken_US
dc.contributor.authorThomas, Ken_US
dc.contributor.authorWeilert, Den_US
dc.contributor.authorYap, TAen_US
dc.contributor.authorPlummer, Ren_US
dc.date.accessioned2018-02-14T14:46:29Z
dc.date.issued2018-04en_US
dc.identifier.citationJournal of clinical pharmacology, 2018, 58 (4), pp. 474 - 484en_US
dc.identifier.issn0091-2700en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1077
dc.identifier.eissn1552-4604en_US
dc.identifier.doi10.1002/jcph.1035en_US
dc.description.abstractTwo phase 1, open-label studies assessed the impact of food or gastric pH modification (omeprazole) on the exposure and safety/tolerability of osimertinib and its metabolites. The food effect study was an open-label, 2-period crossover study in patients with advanced non-small-cell lung cancer, randomized into 2 treatment sequences: single-dose osimertinib 80 mg in a fed then fasted state or fasted then fed. The gastric pH study was an open-label, 2-period fixed sequence study assessing the effect of omeprazole on osimertinib exposure in healthy male volunteers. In period 1, volunteers received omeprazole 40 mg (days 1-4), then omeprazole 40 mg plus osimertinib 80 mg (day 5). In period 2, volunteers received osimertinib 80 mg alone (single dose). Blood samples were collected at prespecified time points for pharmacokinetic analyses. Safety/tolerability was also assessed. In the food effect study 38 patients were randomized to fed/fasted (n = 18) or fasted/fed (n = 20) sequences with all patients completing treatment. Coadministration with food did not affect osimertinib exposure (geometric least-squares mean ratios [90% confidence intervals]: 106.05% [94.82%, 118.60%] [area under the plasma concentration time curve from zero to 72 hours] and 92.75% [81.40%, 105.68%] [maximum plasma concentration]). In the gastric pH study (n = 68 received treatment, n = 47 completed the study), coadministration with omeprazole did not affect osimertinib exposure (geometric least-squares mean ratios 106.66% [100.26%, 113.46%] [area under the concentration-time curve], 101.65% [94.65%, 109.16%] [peak concentration]). Osimertinib was well tolerated in both studies. Osimertinib may be administered without regard to food. Dose restriction is not required in patients whose gastric pH may be altered by concomitant agents or medical conditions. ClinicalTrials.gov: NCT02224053, NCT02163733.en_US
dc.formatPrint-Electronicen_US
dc.format.extent474 - 484en_US
dc.languageengen_US
dc.language.isoengen_US
dc.subjectHumansen_US
dc.subjectCarcinoma, Non-Small-Cell Lungen_US
dc.subjectLung Neoplasmsen_US
dc.subjectPiperazinesen_US
dc.subjectOmeprazoleen_US
dc.subjectAntineoplastic Agentsen_US
dc.subjectProtein Kinase Inhibitorsen_US
dc.subjectFastingen_US
dc.subjectCross-Over Studiesen_US
dc.subjectDrug Interactionsen_US
dc.subjectFooden_US
dc.subjectAdolescenten_US
dc.subjectAdulten_US
dc.subjectAgeden_US
dc.subjectAged, 80 and overen_US
dc.subjectMiddle Ageden_US
dc.subjectFemaleen_US
dc.subjectMaleen_US
dc.subjectProton Pump Inhibitorsen_US
dc.subjectYoung Adulten_US
dc.subjectHealthy Volunteersen_US
dc.titleThe Effect of Food or Omeprazole on the Pharmacokinetics of Osimertinib in Patients With Non-Small-Cell Lung Cancer and in Healthy Volunteers.en_US
dc.typeJournal Article
dcterms.dateAccepted2017-09-22en_US
rioxxterms.versionofrecord10.1002/jcph.1035en_US
rioxxterms.licenseref.startdate2018-04en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfJournal of clinical pharmacologyen_US
pubs.issue4en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicine Drug Development Unit (de Bono)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine Drug Development Unit (de Bono)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublisheden_US
pubs.volume58en_US
pubs.embargo.termsNot knownen_US
icr.researchteamMedicine Drug Development Unit (de Bono)en_US
dc.contributor.icrauthorYap, Timothyen_US
dc.contributor.icrauthorMarsden,en_US


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