Trial Outcomes & Findings for A Phase I, Open-label Study to Assess Bioavailability of a Single Oral Dose of AZD9291 vs an IV Dose of [14C]AZD9291 (NCT NCT02491944)

NCT ID: NCT02491944

Last Updated: 2016-10-13

Results Overview

Absolute bioavailability of AZD9291 will be calculated from area under the plasma concentration versus time curve (AUC) of the oral dose of AZD9291 / AUC of the IV dose of \[14C\]AZD9291 x IV dose/Oral dose x 100

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 27 participants
• Primary outcome timeframe: Samples taken at pre-dose, 1, 2, 3, 4, 5:45, 5:52, 6, 6:05, 6:10, 6:20, 6:25, 6:30, 7, 8, 9, 10, 12, 14, 16, 18, 24, 30, 48, 72, 120, 168, 216, 336 and 504 hours relative to the oral dose.
• Results posted on: 2016-10-13

Participant Flow

First subject enrolled: 10 July 2015; Last subject last visit: 26 August 2015. This study was conducted in a single study centre in the UK.

27 subjects were enrolled (signed informed consent). Subjects were assigned to treatment if they met all the inclusion and none of the exclusion criteria. 17 subjects were enrolled but failed inclusion/exclusion criteria and so were not eligible to be assigned treatment. The remaining 10 subjects received treatment.

Participant milestones

Measure	AZD9291 and [14C]AZD9291 Single oral dose of 80 mg AZD9291 tablet on Day 1 and 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.
Overall Study STARTED	10
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	AZD9291 and [14C]AZD9291 n=10 Participants Single oral dose of 80 mg AZD9291 tablet on Day 1 and 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.
Age, Continuous	34.8 Years STANDARD_DEVIATION 13.29 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Samples taken at pre-dose, 1, 2, 3, 4, 5:45, 5:52, 6, 6:05, 6:10, 6:20, 6:25, 6:30, 7, 8, 9, 10, 12, 14, 16, 18, 24, 30, 48, 72, 120, 168, 216, 336 and 504 hours relative to the oral dose.

Population: PK analysis set included all healthy male subjects who received at least 1 dose of AZD9291 and have at least 1 post-dose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of AZD9291.

Absolute bioavailability of AZD9291 will be calculated from area under the plasma concentration versus time curve (AUC) of the oral dose of AZD9291 / AUC of the IV dose of [14C]AZD9291 x IV dose/Oral dose x 100

Outcome measures

Measure	AZD9291 and [14C]AZD9291 n=10 Participants Single oral dose of 80 mg AZD9291 tablet on Day 1 and 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.
Absolute Oral Bioavailability	69.75 Percentage Interval 66.71 to 72.92

SECONDARY outcome

Timeframe: Samples taken at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 and 504 hours post-dose.

Population: PK analysis set included all healthy male subjects who received at least 1 dose of AZD9291 and have at least 1 post-dose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of AZD9291.

Pharmacokinetic (PK) profile of the oral dose of AZD9291 in terms of Area under the plasma concentration - time curve (AUC) from zero to infinity for AZD9291 and it's metabolites AZ5104 and AZ7550.

Outcome measures

Measure	AZD9291 and [14C]AZD9291 n=10 Participants Single oral dose of 80 mg AZD9291 tablet on Day 1 and 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.
AUC for AZD9291 and it's Metabolites AZ5104 and AZ7550 AZD9291	6791 nM*h Geometric Coefficient of Variation 27.6
AUC for AZD9291 and it's Metabolites AZ5104 and AZ7550 AZ5104	694.5 nM*h Geometric Coefficient of Variation 37.6
AUC for AZD9291 and it's Metabolites AZ5104 and AZ7550 AZ7550	602.5 nM*h Geometric Coefficient of Variation 28.6

SECONDARY outcome

Timeframe: Samples taken at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 and 504 hours post-dose.

Population: PK analysis set included all healthy male subjects who received at least 1 dose of AZD9291 and have at least 1 post-dose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of AZD9291.

Pharmacokinetic (PK) profile of the oral dose of AZD9291 in terms of Area under the plasma concentration - time curve (AUC) from time zero to 24 hours (AUC 0-24) for AZD9291 and it's metabolites AZ5104 and AZ7550.

Outcome measures

Measure	AZD9291 and [14C]AZD9291 n=10 Participants Single oral dose of 80 mg AZD9291 tablet on Day 1 and 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.
AUC(0-24) for AZD9291 and it's Metabolites AZ5104 and AZ7550 AZD9291	1963 nM*h Geometric Coefficient of Variation 26.6
AUC(0-24) for AZD9291 and it's Metabolites AZ5104 and AZ7550 AZ5104	113.7 nM*h Geometric Coefficient of Variation 40.1
AUC(0-24) for AZD9291 and it's Metabolites AZ5104 and AZ7550 AZ7550	75.38 nM*h Geometric Coefficient of Variation 33.8

SECONDARY outcome

Timeframe: Samples taken at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 and 504 hours post-dose.

Population: PK analysis set included all healthy male subjects who received at least 1 dose of AZD9291 and have at least 1 post-dose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of AZD9291.

Pharmacokinetic (PK) profile of the oral dose of AZD9291 in terms of Area under the plasma concentration - time curve (AUC) from time zero to 120 hours (AUC 0-120) for AZD9291 and it's metabolites AZ5104 and AZ7550.

Outcome measures

Measure	AZD9291 and [14C]AZD9291 n=10 Participants Single oral dose of 80 mg AZD9291 tablet on Day 1 and 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.
AUC(0-120) for AZD9291 and it's Metabolites AZ5104 and AZ7550 AZD9291	5545 nM*h Geometric Coefficient of Variation 25.3
AUC(0-120) for AZD9291 and it's Metabolites AZ5104 and AZ7550 AZ5104	512.9 nM*h Geometric Coefficient of Variation 37.2
AUC(0-120) for AZD9291 and it's Metabolites AZ5104 and AZ7550 AZ7550	361.8 nM*h Geometric Coefficient of Variation 28.8

SECONDARY outcome

Timeframe: Samples taken at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 and 504 hours post-dose.

Population: PK analysis set included all healthy male subjects who received at least 1 dose of AZD9291 and have at least 1 post-dose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of AZD9291.

Pharmacokinetic (PK) profile of the oral dose of AZD9291 in terms of Area under the plasma concentration - time curve (AUC) from time zero to the last quantifiable concentration (AUC 0-t) for AZD9291 and it's metabolites AZ5104 and AZ7550.

Outcome measures

Measure	AZD9291 and [14C]AZD9291 n=10 Participants Single oral dose of 80 mg AZD9291 tablet on Day 1 and 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.
AUC(0-t) for AZD9291 and it's Metabolites AZ5104 and AZ7550 AZD9291	6770 nM*h Geometric Coefficient of Variation 27.6
AUC(0-t) for AZD9291 and it's Metabolites AZ5104 and AZ7550 AZ5104	684.4 nM*h Geometric Coefficient of Variation 37.6
AUC(0-t) for AZD9291 and it's Metabolites AZ5104 and AZ7550 AZ7550	591.2 nM*h Geometric Coefficient of Variation 29.0

SECONDARY outcome

Timeframe: Samples taken at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 and 504 hours post-dose.

Population: PK analysis set included all healthy male subjects who received at least 1 dose of AZD9291 and have at least 1 post-dose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of AZD9291.

PK profile of the oral dose of AZD9291 in terms of the maximum observed plasma concentration (Cmax) for AZD9291 and it's metabolites AZ5104 and AZ7550.

Outcome measures

Measure	AZD9291 and [14C]AZD9291 n=10 Participants Single oral dose of 80 mg AZD9291 tablet on Day 1 and 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.
Cmax for AZD9291 and it's Metabolites AZ5104 and AZ7550 AZD9291	118.0 nM Geometric Coefficient of Variation 28.1
Cmax for AZD9291 and it's Metabolites AZ5104 and AZ7550 AZ5104	6.187 nM Geometric Coefficient of Variation 38.0
Cmax for AZD9291 and it's Metabolites AZ5104 and AZ7550 AZ7550	4.302 nM Geometric Coefficient of Variation 34.3

SECONDARY outcome

Timeframe: Samples taken at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 and 504 hours post-dose.

Population: PK analysis set included all healthy male subjects who received at least 1 dose of AZD9291 and have at least 1 post-dose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of AZD9291.

PK profile of the oral dose of AZD9291 in terms of the time to maximum observed plasma concentration (Tmax) for AZD9291 and it's metabolites AZ5104 and AZ7550.

Outcome measures

Measure	AZD9291 and [14C]AZD9291 n=10 Participants Single oral dose of 80 mg AZD9291 tablet on Day 1 and 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.
Tmax for AZD9291 and it's Metabolites AZ5104 and AZ7550 AZD9291	7.01 hours Full Range 28.1 • Interval 6.0 to 10.0
Tmax for AZD9291 and it's Metabolites AZ5104 and AZ7550 AZ5104	12.00 hours Full Range 38.0 • Interval 6.0 to 48.07
Tmax for AZD9291 and it's Metabolites AZ5104 and AZ7550 AZ7550	11.03 hours Full Range 34.3 • Interval 8.0 to 48.0

SECONDARY outcome

Timeframe: Samples taken at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 and 504 hours post-dose.

Population: PK analysis set included all healthy male subjects who received at least 1 dose of AZD9291 and have at least 1 post-dose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of AZD9291.

PK profile of the oral dose of AZD9291 in terms of the elimination half life (t1/2,λz) for AZD9291 and it's metabolites AZ5104 and AZ7550.

Outcome measures

Measure	AZD9291 and [14C]AZD9291 n=10 Participants Single oral dose of 80 mg AZD9291 tablet on Day 1 and 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.
t1/2,λz for AZD9291 and it's Metabolites AZ5104 and AZ7550 AZD9291	59.72 hours Standard Deviation 4.257 • Interval 6.0 to 10.0
t1/2,λz for AZD9291 and it's Metabolites AZ5104 and AZ7550 AZ5104	52.59 hours Standard Deviation 7.355 • Interval 6.0 to 48.07
t1/2,λz for AZD9291 and it's Metabolites AZ5104 and AZ7550 AZ7550	72.58 hours Standard Deviation 11.86 • Interval 8.0 to 48.0

SECONDARY outcome

Timeframe: Samples taken at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 and 504 hours post-dose.

Population: PK analysis set included all healthy male subjects who received at least 1 dose of AZD9291 and have at least 1 post-dose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of AZD9291.

PK profile of the oral dose of AZD9291 in terms of apparent total body clearance of drug from plasma after extravascular administration(CL/F) for AZD9291.

Outcome measures

Measure	AZD9291 and [14C]AZD9291 n=10 Participants Single oral dose of 80 mg AZD9291 tablet on Day 1 and 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.
CL/F for AZD9291	24.40 L/h Standard Deviation 6.979 • Interval 6.0 to 10.0

SECONDARY outcome

Timeframe: Samples taken pre-dose, during the infusion, immediately at the end of infusion and then at 5, 10, 20, 25 and 30 minutes and 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 42, 66, 114, 162, 210, 330 and 498 hours after the end of the infusion.

Population: PK analysis set included all healthy male subjects who received at least 1 dose of AZD9291 and have at least 1 post-dose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of AZD9291.

Pharmacokinetic (PK) profile of the IV dose of AZD9291 in terms of Area under the plasma concentration - time curve (AUC) from zero to infinity for [14C]AZD9291 and it's metabolites [14C]AZ5104 and [14C]AZ7550.

Outcome measures

Measure	AZD9291 and [14C]AZD9291 n=10 Participants Single oral dose of 80 mg AZD9291 tablet on Day 1 and 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.
AUC for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550 [14C]AZD9291	12.12 nM*eq*h Geometric Coefficient of Variation 22.8
AUC for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550 [14C]AZ5104	1.247 nM*eq*h Geometric Coefficient of Variation 26.8
AUC for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550 [14C]AZ7550	1.177 nM*eq*h Geometric Coefficient of Variation 19.9

SECONDARY outcome

Timeframe: Samples taken pre-dose, during the infusion, immediately at the end of infusion and then at 5, 10, 20, 25 and 30 minutes and 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 42, 66, 114, 162, 210, 330 and 498 hours after the end of the infusion.

Population: PK analysis set included all healthy male subjects who received at least 1 dose of AZD9291 and have at least 1 post-dose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of AZD9291.

Pharmacokinetic (PK) profile of the IV dose of AZD9291 in terms of Area under the plasma concentration - time curve (AUC) from time zero to 24 hours (AUC 0-24) for [14C]AZD9291 and it's metabolites [14C]AZ5104 and [14C]AZ7550.

Outcome measures

Measure	AZD9291 and [14C]AZD9291 n=10 Participants Single oral dose of 80 mg AZD9291 tablet on Day 1 and 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.
AUC(0-24) for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550 [14C]AZD9291	3.463 nM*eq*h Geometric Coefficient of Variation 21.6
AUC(0-24) for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550 [14C]AZ5104	0.1172 nM*eq*h Geometric Coefficient of Variation 36.1
AUC(0-24) for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550 [14C]AZ7550	0.08919 nM*eq*h Geometric Coefficient of Variation 28.5

SECONDARY outcome

Timeframe: Samples taken pre-dose, during the infusion, immediately at the end of infusion and then at 5, 10, 20, 25 and 30 minutes and 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 42, 66, 114, 162, 210, 330 and 498 hours after the end of the infusion.

Population: PK analysis set included all healthy male subjects who received at least 1 dose of AZD9291 and have at least 1 post-dose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of AZD9291.

Pharmacokinetic (PK) profile of the IV dose of AZD9291 in terms of Area under the plasma concentration - time curve (AUC) from time zero to 120 hours (AUC 0-120) for [14C]AZD9291 and it's metabolites [14C]AZ5104 and [14C]AZ7550.

Outcome measures

Measure	AZD9291 and [14C]AZD9291 n=10 Participants Single oral dose of 80 mg AZD9291 tablet on Day 1 and 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.
AUC(0-120) for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550 [14C]AZD9291	9.551 nM*eq*h Geometric Coefficient of Variation 22.1
AUC(0-120) for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550 [14C]AZ5104	0.7450 nM*eq*h Geometric Coefficient of Variation 34.4
AUC(0-120) for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550 [14C]AZ7550	0.5292 nM*eq*h Geometric Coefficient of Variation 28.9

SECONDARY outcome

Timeframe: Samples taken pre-dose, during the infusion, immediately at the end of infusion and then at 5, 10, 20, 25 and 30 minutes and 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 42, 66, 114, 162, 210, 330 and 498 hours after the end of the infusion.

Population: PK analysis set included all healthy male subjects who received at least 1 dose of AZD9291 and have at least 1 post-dose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of AZD9291.

Pharmacokinetic (PK) profile of the IV dose of AZD9291 in terms of Area under the plasma concentration - time curve (AUC) from time zero to the last quantifiable concentration (AUC 0-t) for [14C]AZD9291 and it's metabolites [14C]AZ5104 and [14C]AZ7550.

Outcome measures

Measure	AZD9291 and [14C]AZD9291 n=10 Participants Single oral dose of 80 mg AZD9291 tablet on Day 1 and 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.
AUC(0-t) for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550 [14C]AZD9291	11.64 nM*eq*h Geometric Coefficient of Variation 25.7
AUC(0-t) for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550 [14C]AZ5104	0.8802 nM*eq*h Geometric Coefficient of Variation 44.2
AUC(0-t) for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550 [14C]AZ7550	0.6899 nM*eq*h Geometric Coefficient of Variation 38.1

SECONDARY outcome

Timeframe: Samples taken pre-dose, during the infusion, immediately at the end of infusion and then at 5, 10, 20, 25 and 30 minutes and 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 42, 66, 114, 162, 210, 330 and 498 hours after the end of the infusion.

Population: PK analysis set included all healthy male subjects who received at least 1 dose of AZD9291 and have at least 1 post-dose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of AZD9291.

Pharmacokinetic (PK) profile of the IV dose of AZD9291 in terms of the maximum observed plasma concentration (Cmax) for [14C]AZD9291 and it's metabolites [14C]AZ5104 and [14C]AZ7550.

Outcome measures

Measure	AZD9291 and [14C]AZD9291 n=10 Participants Single oral dose of 80 mg AZD9291 tablet on Day 1 and 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.
Cmax for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550 [14C]AZD9291	0.5762 nM*eq Geometric Coefficient of Variation 68.6
Cmax for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550 [14C]AZ5104	0.008309 nM*eq Geometric Coefficient of Variation 36.1
Cmax for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550 [14C]AZ7550	0.005751 nM*eq Geometric Coefficient of Variation 34.2

SECONDARY outcome

Timeframe: Samples taken pre-dose, during the infusion, immediately at the end of infusion and then at 5, 10, 20, 25 and 30 minutes and 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 42, 66, 114, 162, 210, 330 and 498 hours after the end of the infusion.

Population: PK analysis set included all healthy male subjects who received at least 1 dose of AZD9291 and have at least 1 post-dose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of AZD9291.

Pharmacokinetic (PK) profile of the IV dose of AZD9291 in terms of the the time to maximum observed plasma concentration (Tmax) for [14C]AZD9291 and it's metabolites [14C]AZ5104 and [14C]AZ7550.

Outcome measures

Measure	AZD9291 and [14C]AZD9291 n=10 Participants Single oral dose of 80 mg AZD9291 tablet on Day 1 and 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.
Tmax for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550 [14C]AZD9291	0.25 hours Full Range 68.6 • Interval 0.12 to 0.67
Tmax for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550 [14C]AZ5104	42.25 hours Full Range 36.1 • Interval 12.25 to 66.37
Tmax for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550 [14C]AZ7550	33.27 hours Full Range 34.2 • Interval 18.27 to 66.37

SECONDARY outcome

Timeframe: Samples taken pre-dose, during the infusion, immediately at the end of infusion and then at 5, 10, 20, 25 and 30 minutes and 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 42, 66, 114, 162, 210, 330 and 498 hours after the end of the infusion.

Population: PK analysis set included all healthy male subjects who received at least 1 dose of AZD9291 and have at least 1 post-dose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of AZD9291.

Pharmacokinetic (PK) profile of the IV dose of AZD9291 in terms of the elimination half life (t1/2,λz) for [14C]AZD9291 and it's metabolites [14C]AZ5104 and [14C]AZ7550.

Outcome measures

Measure	AZD9291 and [14C]AZD9291 n=10 Participants Single oral dose of 80 mg AZD9291 tablet on Day 1 and 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.
t1/2,λz for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550 [14C]AZD9291	54.93 hours Standard Deviation 9.032 • Interval 0.12 to 0.67
t1/2,λz for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550 [14C]AZ5104	68.35 hours Standard Deviation 15.73 • Interval 12.25 to 66.37
t1/2,λz for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550 [14C]AZ7550	99.69 hours Standard Deviation 29.33 • Interval 18.27 to 66.37

SECONDARY outcome

Timeframe: Samples taken pre-dose, during the infusion, immediately at the end of infusion and then at 5, 10, 20, 25 and 30 minutes and 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 42, 66, 114, 162, 210, 330 and 498 hours after the end of the infusion.

Population: PK analysis set included all healthy male subjects who received at least 1 dose of AZD9291 and have at least 1 post-dose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of AZD9291.

Pharmacokinetic (PK) profile of the IV dose of AZD9291 in terms of total body clearance of drug from plasma after intravascular administration (CL) for [14C]AZD9291.

Outcome measures

Measure	AZD9291 and [14C]AZD9291 n=10 Participants Single oral dose of 80 mg AZD9291 tablet on Day 1 and 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.
CL for [14C]AZD9291	16.84 L/h Standard Deviation 3.941 • Interval 0.12 to 0.67

Adverse Events

AZD9291 and [14C]AZD9291

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	AZD9291 and [14C]AZD9291 n=10 participants at risk Single oral dose of 80 mg AZD9291 tablet on Day 1 and 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.
Respiratory, thoracic and mediastinal disorders Cough	10.0% 1/10 • Number of events 1 • Adverse events were collected for 30 days starting from the dosing day Regular investigator assessment at study visits.
Gastrointestinal disorders Diarrhoea	10.0% 1/10 • Number of events 1 • Adverse events were collected for 30 days starting from the dosing day Regular investigator assessment at study visits.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	10.0% 1/10 • Number of events 2 • Adverse events were collected for 30 days starting from the dosing day Regular investigator assessment at study visits.

Additional Information

Dr Karen So

AstraZeneca

Email: ClinicalTrialTransparency@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Principal Investigator (PI) agrees to collaborate on the contents and formation of any publication and to pay due consideration to comments and opinions offered. AstraZeneca have 30 days for final manuscript review and may require that submission for publication be delayed in order to file patent application.
• Publication restrictions are in place

Restriction type: OTHER