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dc.contributor.authorVishwanathan, K
dc.contributor.authorDickinson, PA
dc.contributor.authorBui, K
dc.contributor.authorCassier, PA
dc.contributor.authorGreystoke, A
dc.contributor.authorLisbon, E
dc.contributor.authorMoreno, V
dc.contributor.authorSo, K
dc.contributor.authorThomas, K
dc.contributor.authorWeilert, D
dc.contributor.authorYap, TA
dc.contributor.authorPlummer, R
dc.date.accessioned2018-02-14T14:46:29Z
dc.date.issued2018-04
dc.identifier.citationJournal of clinical pharmacology, 2018, 58 (4), pp. 474 - 484
dc.identifier.issn0091-2700
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1077
dc.identifier.eissn1552-4604
dc.identifier.doi10.1002/jcph.1035
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.
dc.formatPrint-Electronic
dc.format.extent474 - 484
dc.languageeng
dc.language.isoeng
dc.subjectHumans
dc.subjectCarcinoma, Non-Small-Cell Lung
dc.subjectLung Neoplasms
dc.subjectPiperazines
dc.subjectOmeprazole
dc.subjectAntineoplastic Agents
dc.subjectProtein Kinase Inhibitors
dc.subjectFasting
dc.subjectCross-Over Studies
dc.subjectDrug Interactions
dc.subjectFood
dc.subjectAdolescent
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectProton Pump Inhibitors
dc.subjectYoung Adult
dc.subjectHealthy Volunteers
dc.titleThe Effect of Food or Omeprazole on the Pharmacokinetics of Osimertinib in Patients With Non-Small-Cell Lung Cancer and in Healthy Volunteers.
dc.typeJournal Article
dcterms.dateAccepted2017-09-22
rioxxterms.versionofrecord10.1002/jcph.1035
rioxxterms.licenseref.startdate2018-04
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfJournal of clinical pharmacology
pubs.issue4
pubs.notesNot known
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.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-statusPublished
pubs.volume58
pubs.embargo.termsNot known
icr.researchteamMedicine Drug Development Unit (de Bono)en_US
dc.contributor.icrauthorYap, Timothyen
dc.contributor.icrauthorMarsden,en


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