Investigation in volunteers only
Conditions
Interventions
Trade Name: Tarceva
Product Name: Erlotinib
Pharmaceutical Form: Tablet
INN or Proposed INN: ERLOTINIB HYDROCHLORIDE
CAS Number: 183319-69-9
Current Sponsor code: Ro 50-8231
Concentration unit: mg mil
Sponsors
Medizinische Universiät Wien
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Non-smokers • Age: >18 and =65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: • Smokers • Abnormalities found in blood and urine laboratory tests as part of the pretreatment screening or in any of the laboratory tests performed that the investigator considers clinically relevant • Presence of any ECG abnormalities, which the investigator considers clinically relevant • Abnormalities in the medical history (e.g. history of or current ethanol abuse, allergies, co-morbidities, anticoagulation with Marcoumar®) that might influence the outcome of the study or might result in inacceptable risks for the subject according to investigators judgment. • History of drug and alcohol abuse • Contraindication to arterial cannulation (e.g. intake of anticoagulants of any kind) • Blood donation within 1 month before the start of the study • Participation in a clinical study with radioactive substances if exposure exceeds the maximum foreseen radiation of the current guidelines • Intake of any medication during two weeks before the start of the study, which the investigator considers may affect the validity of the study, due to interference with CYP3A4, ABCB1 or ABCG2 (ABCB1 inducers such as St. John’s wort, docetaxel, etoposide, vincristine, cyclosporine, tacrolimus, macrolides, lovastatin, digoxin, digitoxin, carvedilol, rifampicin or inhibitors such as esomprazol, omeprazole, pantoprazole, lansoprazole, atorvastatin, itraconazol) or may cause potential harm to the subject (drug-drug interaction between tariquidar and loperamide or quinidine) • Subjects with Galactose-Intolerance, Lactase-Deficiency or Glucose-Galactose –Malabsorption (erlotinib tablets contain lactose) • For female subjects in child-bearing age: Pregnancy or breastfeeding • Exclusion criteria for patients of group 5 only: o A medical condition or drug treatment interfering with the study objectives (at investigators´ discretion) o Absolute contraindication for PET/MRI investigation o Patients with history of alcohol abuse who are currently abstinent o Presence of any ECG or other abnormalities, which the investigator considers clinically relevant o Participation in a clinical study with radioactive substances if exposure exceeds the maximum foreseen radiation of the current guidelines
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: ?To compare distribution of [11C]erlotinib to the brain and to peripheral organs (liver, gall bladder, intestine, kidneys, lungs) without and with co-administration of a therapeutic dose of erlotinib ?To compare distribution of [11C]erlotinib to peripheral organs without and with co-administration of a therapeutic dose of rifampicin ?To investigate whether PET with a microdose of [11C]erlotinib can predict tissue distribution of a therapeutic dose of erlotinib ?To compare distribution of [11C]erlotinib to the brain and to peripheral organs (liver, gall bladder, intestine, kidneys, lungs) without and with co-administration of the ABCB1 inhibitor tariquidar ?To obtain information regarding whole-body radiation dosimetry of [11C]erlotinib in humans ?To assess the utility of [11C]erlotinib for visualization of ABC transporters (ABCB1, ABCG2) at the human BBB and other peripheral organs ??To assess image derived input function for liver blood vessels with PET/MR ;Secondary Objective: ?To assess the safety and tolerability of [11C]erlotinib PET ?To assess radiolabelled metabolites of [11C]erlotinib in plasma ?To develop a kinetic model for quantification of [11C]erlotinib PET data in brain and peripheral organs ?To investigate whole-body biodistribution of [11C]erlotinib in humans ?To assess possible gender differences in [11C]erlotinib distribution ?To assess a dose-response relationship for enhancement of [11C]erlotinib PET signal in the brain after 300-1000 mg erlotinib p.o.- ?To investigate the feasibility of MR based assessment of liver blood flow.;Primary end point(s): ?Outcome parameters from pharmacokinetic modelling of [11C]erlotinib PET data (total volume of distribution VT, rate constants for transfer of [11C]erlotinib between plasma and organ compartments) ?Changes in [11C]erlotinib modelling outcome parameters in scans acquired after erlotinib and during tariquidar administration compared to outcome parameters measured before erlotinib a | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? Influence of erlotinib and tariquidar administration on percentage of radiolabelled metabolites in plasma ? Safety and tolerability of [11C]erlotinib PET imaging ? Whole-body distribution of [11C]erlotinib expressed as SUV ? Sex differences in [11C]erlotinib distribution ? ABCB1/ABCG2 genotype of the study participants;Timepoint(s) of evaluation of this end point: End of Study | — |
Countries
Austria
Contacts
Public ContactKlinische Pharmakologie
Medizinische Universität Wien
Outcome results
None listed