This is a 2 part study in patients with EGFRm+ non small cell lung cancer (NSCLC), whose disease has progressed on an EGFRm TKI, who are refractory or resistant to standard therapy. Part A will assess the effect of multiple oral doses of itraconazole on the single dose pharmacokinetic (PK) parameters of AZD9291. On completion of Part A, patients may continue to take AZD9291 tablets (Part B) following the collection of the 216 hour sample on Day 19 if they and the Investigator deem it appropriate, until such time as their disease progresses, the Investigator believes they are no longer deriving clinical benefit, or they stop taking AZD9291 for any other reason
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
39
Blood samples taken pre and post dosing with AZD9291+/- itraconazole
AZD9291 tablets: Part A 80mg od, days 1 and 10 only. Part B 80mg od for 12 months.
Itraconazole tablets: 2x100mg bd, Part A days 6 to 19 only
Research Site
San Diego, California, United States
Research Site
Cleveland, Ohio, United States
Research Site
Edegem, Belgium
Research Site
Ghent, Belgium
Research Site
Amsterdam, Netherlands
Research Site
Maastricht, Netherlands
Research Site
Rotterdam, Netherlands
Research Site
lJongno-gu, South Korea
Research Site
Seongnam-si, South Korea
Research Site
Seoul, South Korea
...and 6 more locations
Cmax of AZD9291
Pharmacokinetics of AZD9291 by assessment of maximum plasma AZD9291 concentration
Time frame: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.
AUC of AZD9291
Pharmacokinetics of AZD9291 by assessment of area under the plasma concentration time curve from zero to infinity
Time frame: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.
AUC(0-120) of AZD9291
Pharmacokinetics of AZD9291 by assessment of area under the plasma concentration time curve from zero to 120 hours
Time frame: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.
AUC(0-t) of AZD9291
Pharmacokinetics of AZD9291 by assessment of area under the plasma concentration curve from time zero to last quantifiable dose
Time frame: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.
Tmax of AZD9291
Pharmacokinetics of AZD9291 by assessment of time to Cmax
Time frame: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.
t1/2 of AZD9291
Pharmacokinetics of AZD9291 by assessment of the terminal half-life
Time frame: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.
CL/F of AZD9291
Rate and extent of absorption of AZD9291 by assessment of apparent clearance following oral administration
Time frame: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.
Vz/F of AZD9291
Rate and extent of absorption of AZD9291 by assessment of the apprarent volume of distribution
Time frame: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.
Cmax of AZ5104
Pharmacokinetics of AZ5104 (metabolite to AZD9291) by assessment of maximum plasma AZ5104 concentration
Time frame: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.
AUC of AZ5104
Pharmacokinetics of AZ5104 (metabolite to AZD9291) by assessment of area under the plasma concentration time curve from zero to infinity
Time frame: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.
Cmax of AZ7550
Pharmacokinetics of AZ7550 (metabolite to AZD9291) by assessment of maximum plasma AZ7550 concentration
Time frame: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.
AUC of AZ7550
Pharmacokinetics of AZ7550 (metabolite to AZD9291) by assessment of area under the plasma concentration time curve from zero to infinity
Time frame: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.
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