A Phase I, Open-label study to Assess Bioavailability of a Single Oral Dose of AZD9291 vs an IV dose of [14C]AZD9291

Exclusion Criteria

• 1. Involvement in planning and/or conduct of study.
• 2. Subjects previously enrolled in this study.
• 3. History of clinically significant disease or disorder which, either puts subject at risk because of participation in study, or influences results or subject’s ability to participate in study.
• 4. History or presence of condition known to interfere with ADME of drugs.
• 5. Any clinically significant abnormalities in physical examination, as judged by PI.
• 6. Acute illness, surgical procedures, or trauma from within 2 wks before screening until first admin of investigational product (IMP).
• 7. Subjects who have received live or live-attenuated vaccine in 2 wks prior to IMP admin.
• 8. Subjects with active malignancy or neoplastic disease in previous 12 mths.
• 9. A suspected/manifested infection according to IATA Categories A and B.
• 10. Positive screening tests for serum hepatitis B surface antigen, hepatitis C antibody, or HIV.
• 11. Any clinically important abnormalities in rhythm, conduction, or morphology of resting 12-lead ECG, QT interval >470 ms.
• 12. Known or suspected history of significant drug abuse.
• 13. Positive screen for drugs of abuse or cotinine at screening or positive screen for alcohol, drugs of abuse, or cotinine on admission to centre prior to first admin of IMP.
• 14. History of alcohol abuse or excessive intake of alcohol, defined as regular weekly intake of more than 21 units of alcohol in men
• 15. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by PI, or history of hypersensitivity to AZD9291, its excipients, or drugs with a similar chemical structure or class.
• 16. Use of any prescribed or non-prescribed medication, including drugs during the 4 wks (or longer depending on the medication’s half-life) prior to admin of AZD9291 is not permitted. Occasional use of paracetamol and adrenergic nasal spray for relief of nasal congestion is permitted at the discretion of the PI. Exceptions as agreed by PI and sponsor’s medical monitor if do not interfere with aims of study.
• 17. Use of drugs with enzyme inducing properties such as St John’s Wort within 4 wks prior to IMP administration.
• 18. Any intake of grapefruit, grapefruit juice, Seville oranges or products containing these fruit within 7 days of first admin of IMP.
• 19. Blood donation within 1 mth of screening or any blood donation/blood loss greater than 500 mL during 3 mths prior to screening.
• 20. Subjects who received another NCE or participated in any other clinical study (including methodology studies where no drugs were given) within 3 mths of first admin of IMP
• 21. Judgment by PI that subject should not participate in study if subject is considered unlikely to comply with study procedures, restrictions, and requirements.
• 22. Ongoing or planned inpatient surgery, dental procedure, or hospitalisation during study
• 23. Radiation exposure exceeding 5 mSv in last 12 mths or 10 mSv in last 5 yrs.
• 24. Admin of any amount of a [14C]-labelled compound within last 12 mths.
• 25. Used of nicotine products (including cigarettes) within previous 3 mths.
• 26. Judgment by PI that subject would not be able to understand or cooperate with requirements of study.
• 27. Previous bone marrow transplant
• 28. Blood transfusion within 120 days of genetic sample collection