A Phase I, Open-label Study to Assess Bioavailability of a Single Oral Dose of AZD9291 vs an IV Dose of [14C]AZD9291
Condition: Oncology
MeSH terms: Neoplasms
Intervention: AZD9291; [14C]AZD9291
Intervention description: Single oral dose of 80 mg AZD9291 tablet on Day 1 administered orally with 240 mL water following an overnight fast.; Each healthy male subject will also receive a single, radiolabeled, 100 μg dose of [14C] AZD9291 administered as an IV microdose infusion starting at 5 hours and 45 minutes after receiving the oral dose.
Intervention MeSH terms: Osimertinib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 27.0
Sex: Male
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The Sponsor is developing the study drug, AZD9291, for the potential treatment of nonsmall
      cell lung cancer. Lung cancer has been the most common cancer in the world for several
      decades and represents 12.8% of all new cancer cases in 2008.

      The purpose of this study is to see how much AZD9291 is taken up by the body when dosed by
      mouth (tablet) compared to when the study drug is dosed once by injection directly into the
      vein (intravenously). The dose given directly into the vein will be radiolabelled. This means
      that the test drug has a radioactive component which helps us to track where the drug is in
      the body. This allows us to detect the differences between the tablet and the intravenous
      dose.

      The study will be performed in 12 healthy male subjects aged 18-65 years. On Day 1, subjects
      will be dosed with a single oral dose of 80 milligrams AZD9291 tablet followed by 100
      micrograms [14C] AZD9291 dosed as an intravenous microdose beginning 5 hours and 45 minutes
      after the oral dose has been administered. Subjects will remain in the study centre until
      after the 120 hour post-dose blood sample is obtained and will return to the clinic for
      further visits on Day 8, 10, 15 and 22 for pharmacokinetic and safety assessments.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Signed dated, written informed consent.

          2. Healthy male aged 18 to 65 yrs with suitable veins for blood sampling

          3. BMI: 19 and 32 kg/m2 inclusive, weight at least 50 kg and no more than 100 kg,
             inclusive.

          4. At screening, calculated creatinine clearance ≥50 mL/min using Cockcroft Gault
             formula.

          5. Willing to use defined methods of contraception

          6. Willing and able to comply with study procedures, restrictions and requirements.

          7. Provision of informed consent for genetic research. Declining genetic research will
             not exclude subjects from other aspects of study.

        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