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
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      The study is a Phase I, open label, single dose, single centre study performed in 12 healthy
      male subjects aged 18 to 65 years, inclusive. This study will assess the absolute
      bioavailability of AZD9291 and evaluate the PK parameters following a single oral dose of
      AZD9291 and a radiolabelled IV microdose of AZD9291 in healthy male subjects. Oral AZD9291and
      [14C] AZD9291 intravenous solution are referred to as the investigational products in this
      study.

      A screening visit (Visit 1) to assess the eligibility of the healthy male subjects will occur
      within 28 days of the administration of the investigational product. Screening assessments
      will include evaluation of opthalmological assessments, clinical chemistry, haematology,
      urinalysis, a physical examination, vital signs, 12-lead electrocardiograms (ECGs), medical
      and surgical history, screening for drugs of abuse, alcohol, hepatitis B and C, and HIV, and
      recording of concomitant medications and Adverse Events. Study related procedures will only
      be performed after signing of the Informed Consent Form.

      The healthy male subjects will be admitted to the study centre the day before administration
      of the investigational product (Day 1; Visit 2). On Day 1 (Visit 2), subjects will be dosed
      with a single oral dose of 80 mg AZD9291 tablet followed by 100 μg [14C] AZD9291 dosed as an
      IV microdose beginning 5 hours and 45 minutes after the oral dose has been administered. The
      IV microdose will be infused over 15 minutes and the end of the infusion will be co
      incidental with median oral tmax (ie, estimated tmax is 6 hours).

      The subjects will remain in the study centre until the 120 hour post dose PK blood sample is
      obtained. Ambulatory visits will occur on Days 8 (Visit 3), 10 (Visit 4), 15 (Visit 5) and 22
      (Visit 6) for PK and safety assessments. A follow up visit (Visit 7) will occur 21 to 28 days
      after discharge (Days 27 - 34) from the study centre and will include routine safety
      assessments.
    

Intervention name(s): AZD9291; [14C]AZD9291
Intervention type(s): Drug; Drug
Intervention description(s): 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
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment