Study to Assess the Effect of Osimertinib (TAGRISSO™ ) on Blood Levels of Fexofenadine in Patients With EGFRm+ NSCLC

Study identifier:D5160C00036

ClinicalTrials.gov identifier:NCT02908750

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

An Open-label, Non-randomised, Phase I Study to Assess the Effect of Single and Multiple Oral Doses of Osimertinib (TAGRISSO™) on the Pharmacokinetics of a P-glycoprotein Probe Drug (Fexofenadine) in Patients with Advanced EGFRm NSCLC that have Progressed on a Prior EGFR-TKI Regimen

Medical condition

Non Small Cell Lung Cancer

Phase

Phase 1

Healthy volunteers

Study drug

Fexofenadine tablet dosing, Osimertininb tablet dosing

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 02 Mar 2017

Primary Completion Date: 31 Jul 2017

Study Completion Date: 11 Oct 2022

Study design

Allocation: Non-randomized
Endpoint Classification: Pharmacokinetics
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 Nov 2023 by AstraZeneca

Collaborators

Quintiles

Inclusion and exclusion criteria

Inclusion Criteria

• Male or female, ≥18 years
• Histological or cytological confirmation diagnosis of NSCLC
• Radiological documentation of disease progression while receiving previous continuous treatment with an EGFR-TKI.
• Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR-TKI sensitivity
• ECOG performance status 0 to 1, with no deterioration over the previous 2 weeks.
• Patients must have a life expectancy of 12 weeks or longer
• Females should be using adequate contraceptive measures and must have a negative serum pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child bearing potential.
• Male patients should be willing to use barrier contraception ie, condoms until 6 months after the last study drug is taken.
• For inclusion in optional genetic research, patients must provide separate informed consent.

Exclusion Criteria

• Treatment with any of the following:
o A 1st or 2nd generation EGFR-TKI within 8 days or approximately 5 half-lives, of the first dose of study treatment
o Osimertinib in the present study [ie, dosing with osimertinib previously initiated in this study] or has previously received a 3rd generation EGFR-TKI [eg, CO 1686].
o Any cytotoxic chemotherapy, investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment.
o Major surgery [excluding placement of vascular access] within 4 weeks of the first dose of study treatment.
o Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of study treatment
o Patients currently receiving [or unable to stop at least 3 weeks prior to first dose of osimertinib] medications or herbal supplements known to be potent inducers of CYP3A4 or inducers/inhibitors of P-gp.
• Spinal cord compression or brain metastases, unless asymptomatic, stable and not requiring steroids for at least 4 weeks prior to start of study treatment.
• Any of the following cardiac criteria:
o Mean resting corrected QT interval corrected for heart rate using Fridericia’s correction factor [QTcF] greater than 470 msec, obtained from 3 ECGs.
o Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG [eg, complete left bundle branch block, third degree heart block, second degree heart block, PR interval greater than 250 msec]
o Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval
• Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
• Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
o Absolute neutrophil count [ANC] less than 1.5 × 109/L
o Platelet count less than 100 × 109/L
o Haemoglobin less than 90 g/L
o ALT greater than 2.5 times ULN if no demonstrable liver metastases or greater than 5 times ULN in the presence of liver metastases
o AST greater than 2.5 times ULN if no demonstrable liver metastases or greater than 5 times ULN in the presence of liver metastases
o Total bilirubin greater than 1.5 times ULN if no liver metastases or greater than 3 times ULN in the presence of liver metastases
o Creatinine greater than 1.5 times institutional ULN concurrent with creatinine clearance less than 50 mL/min [measured or calculated by Cockcroft-Gault formula]
• Patients unable to swallow orally administered medication or with gastrointestinal disorders or significant gastrointestinal resection likely to interfere with the absorption of the study drugs.

This is a Phase I, open-label, non-randomised, two-part study in patients with EGFRm+ NSCLC who have progressed on an EGFR-TKI. The PK phase will assess the effect of osimertinib on the PK parameters of fexofenadine following both single and multiple oral dosing of osimertinib. Continued access will provide patients with further access to osimertinib after the PK phase. The study will be conducted at approximately 10 sites across Asia and Western Europe, with approximately 24 patients enrolled in order to achieve at least 18 evaluable patients. Additional patients may be dosed to ensure the minimum number of evaluable patients. PK phase The PK phase is a non-randomised, open-label, 2-period design. Treatment Period 1 and Treatment Period 2 are separated by a 3 to 7 day washout period between doses. A study flow chart for the PK phase is presented in Figure 1. Patients will receive osimertinib 80 mg as a single dose on Day 1 of Treatment Period 2, then 80 mg once daily for 38 days (from Day 4 to Day 41 in Treatment Period 2). Patients will also receive a single oral dose of fexofenadine on Day 1 in Treatment Period 1, and on Days 1 and 39 in Treatment Period 2. Continued access On completion of the PK phase (ie, following collection of the 72-hour fexofenadine sample on Day 42), patients may continue to take osimertinib tablets (80 mg once daily) as a single agent in continued access if they and the Investigator agree that this is appropriate. This will continue until the Investigator believes they are no longer deriving clinical benefit, or they stop taking osimertinib for any other reason. No clinical data will be collected during this phase other than sudden death of unknown reason, serious adverse events (SAEs) that may be related to osimertinib, outcomes of pregnancy and drug dispensing/accountability. If a patient discontinues treatment during the PK phase, they will return to the clinic for follow-up assessments 30 days (±7 days) after their last dose of treatment in the PK phase. If the patient’s last dose of osimertinib is in continued access, the patient should be contacted 30 days after their last dose of osimertinib to follow-up any existing SAEs, monitor for new SAEs that may be related to the IP, and record any sudden deaths of unknown cause.

Location

Research Site

Madrid, Spain, 28050

Location

Research Site

Sevilla, Spain, 41013

Location

Research Site

Seoul, Republic of Korea, 05505

Location

Research Site

Seongnam-si, Republic of Korea, 13620

Location

Research Site

Rennes Cedex 9, France, 35033

Location

Research Site

Madrid, Spain, 28040

Location

Research Site

Madrid, Spain, 28046

Arms	Assigned Interventions
Experimental: osimertinib and fexofenadine Sequential treatments of fexofenadine alone followed by osimertinib + fexofenadine, followed by osimertinib alone, followed by osimertinib + fexofenadine	Drug: Fexofenadine tablet dosing Fexofenadine (P-gp substrate) 120mg taken once daily on Days 1 in Treatment Period 1 and Day 1 and Day 39 in Treatment Period 2 Other Name: Mucinex, Allegra, Select, Rugby Drug: Osimertininb tablet dosing Osimertininb 80 mg taken once daily on Day 1 and Days 4 to 41 in Treatment Period 2 Other Name: TAGRISSO™

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
First patient enrolled: 02 March 2017; last patient completed: 30 July 2017. This study was performed at 7 sites in 3 countries: South Korea, Spain and France. Study assessed effect of AZD9291 on the pharmacokinetics (PK) of fexofenadine (a sensitive P-glycoprotein substrate) after both single and multiple AZD9291 dosing.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
27 patients were enrolled (signed informed consent). 3 were not assigned to treatment as they met an exclusion criterion (n=2) or died before treatment assignment (n=1). The remaining 24 patients received treatment.

Reporting Groups

	Description
AZD9291 and fexofenadine	Sequential treatments of fexofenadine alone (Treatment Period 1) followed by AZD9291 + fexofenadine, followed by AZD9291 alone, followed by AZD9291 + fexofenadine (Treatment Period 2). Patients received a single oral dose of fexofenadine 120 mg on Day 1 of Treatment Period 1. Treatment Period 1 and Treatment Period 2 were separated by a 3 to 7 day washout period between doses. Patients received a second oral dose of fexofenadine 120 mg in combination with a single oral dose of AZD9291 80 mg on Day 1 of Treatment Period 2. Patients then received AZD9291 80 mg once daily from Day 4 to Day 41 inclusive. In addition, patients received a third oral dose of fexofenadine 120 mg on Day 39.

Description

AZD9291 and fexofenadine

Sequential treatments of fexofenadine alone (Treatment Period 1) followed by AZD9291 + fexofenadine, followed by AZD9291 alone, followed by AZD9291 + fexofenadine (Treatment Period 2).
Patients received a single oral dose of fexofenadine 120 mg on Day 1 of Treatment Period 1. Treatment Period 1 and Treatment Period 2 were separated by a 3 to 7 day washout period between doses. Patients received a second oral dose of fexofenadine 120 mg in combination with a single oral dose of AZD9291 80 mg on Day 1 of Treatment Period 2. Patients then received AZD9291 80 mg once daily from Day 4 to Day 41 inclusive. In addition, patients received a third oral dose of fexofenadine 120 mg on Day 39.

Participant Flow: Overall Study

	AZD9291 and fexofenadine
STARTED	24
COMPLETED	21
NOT COMPLETED	3
Progressive disease	2
Death	1

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

All patients in the safety analysis set who received at least one dose of AZD9291 or fexofenadine were included in the baseline analysis.

Reporting Groups

	Description
AZD9291 and fexofenadine	Sequential treatments of fexofenadine alone (Treatment Period 1) followed by AZD9291 + fexofenadine, followed by AZD9291 alone, followed by AZD9291 + fexofenadine (Treatment Period 2). Patients received a single oral dose of fexofenadine 120 mg on Day 1 of Treatment Period 1. Treatment Period 1 and Treatment Period 2 were separated by a 3 to 7 day washout period between doses. Patients received a second oral dose of fexofenadine 120 mg in combination with a single oral dose of AZD9291 80 mg on Day 1 of Treatment Period 2. Patients then received AZD9291 80 mg once daily from Day 4 to Day 41 inclusive. In addition, patients received a third oral dose of fexofenadine 120 mg on Day 39.

Description

AZD9291 and fexofenadine

Sequential treatments of fexofenadine alone (Treatment Period 1) followed by AZD9291 + fexofenadine, followed by AZD9291 alone, followed by AZD9291 + fexofenadine (Treatment Period 2). Patients received a single oral dose of fexofenadine 120 mg on Day 1 of Treatment Period 1. Treatment Period 1 and Treatment Period 2 were separated by a 3 to 7 day washout period between doses. Patients received a second oral dose of fexofenadine 120 mg in combination with a single oral dose of AZD9291 80 mg on Day 1 of Treatment Period 2. Patients then received AZD9291 80 mg once daily from Day 4 to Day 41 inclusive. In addition, patients received a third oral dose of fexofenadine 120 mg on Day 39.

Baseline Measures

	AZD9291 and fexofenadine
Number of Participants [units: Participants]	24
Age Continuous [units: years] Mean ± Standard Deviation	61.7 ± 12.77
Sex: Female, Male [units: participants]
Female	15
Male	9
Race (NIH/OMB) [units: participants]
American Indian or Alaska Native	0
Asian	12
Native Hawaiian or Other Pacific Islander	0
Black or African American	0
White	12
More than one race	0
Unknown or Not Reported	0

Outcome Measures

1. Primary Outcome Measure: Maximum plasma concentration (Cmax) for fexofenadine after dosing alone and in combination with AZD9291 [ Time Frame: Blood samples were collected on Days 1 to 4 in Treatment Period 1, and on Days 1 to 4 and Days 39 to 42 in Treatment Period 2. PK sampling at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 24, 36, 48, 60 and 72 hours post-dose (fexofenadine dosing). ]

Measure Type	Primary
Measure Name	Maximum plasma concentration (Cmax) for fexofenadine after dosing alone and in combination with AZD9291
Measure Description	Rate and extent of absorption of fexofenadine by assessment of Cmax following administration of fexofenadine alone (during Treatment Period 1) and then with AZD9291 as a single dose and as multiple doses (during Treatment Period 2).
Time Frame	Blood samples were collected on Days 1 to 4 in Treatment Period 1, and on Days 1 to 4 and Days 39 to 42 in Treatment Period 2. PK sampling at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 24, 36, 48, 60 and 72 hours post-dose (fexofenadine dosing).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose for any analyte without any important deviations or events that would exclude the patient. Only patients with data available at the timepoints of testing were included in the analyses.

Reporting Groups

	Description
Fexofenadine alone (Treatment Period 1)	Patients received a single oral dose of fexofenadine 120 mg on Day 1 of Treatment Period 1.
Fexofenadine + AZD9291 single dose (Treatment Period 2)	Patients received a single oral dose of fexofenadine 120 mg in combination with a single oral dose of AZD9291 80 mg on Day 1 of Treatment Period 2.
Fexofenadine + AZD9291 multiple dose (Treatment Period 2)	Patients received oral doses of AZD9291 80 mg once daily from Days 4 to 41 inclusive during Treatment Period 2. In addition, patients received a single oral dose of fexofenadine 120 mg on Day 39 of Treatment Period 2.

Measured Values

	Fexofenadine alone (Treatment Period 1)	Fexofenadine + AZD9291 single dose (Treatment Period 2)	Fexofenadine + AZD9291 multiple dose (Treatment Period 2)
Number of Participants Analyzed [units:participants]	24	22	21
Maximum plasma concentration (Cmax) for fexofenadine after dosing alone and in combination with AZD9291 [units: nanograms per millilitre (ng/mL)] Geometric Mean (Geometric Coefficient of Variation)	497.7 (66.9%)	890.9 (55.6%)	615.0 (39.6%)

Statistical Analysis 1 for Maximum plasma concentration (Cmax) for fexofenadine after dosing alone and in combination with AZD9291

Groups^[1]	Fexofenadine alone (Treatment Period 1), Fexofenadine + AZD9291 single dose (Treatment Period 2)
Other^[5]	176.38
90% Confidence Interval	( 149.33 to 208.33 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Natural log-transformed Cmax values were compared between treatments using a linear mixed effects model, with treatment as a fixed effect and patient as a random effect.
[5]	Other relevant estimation information:
	Fexofenadine + AZD9291 single dose versus fexofenadine alone.

Statistical Analysis 2 for Maximum plasma concentration (Cmax) for fexofenadine after dosing alone and in combination with AZD9291

Groups^[1]	Fexofenadine alone (Treatment Period 1), Fexofenadine + AZD9291 multiple dose (Treatment Period 2)
Other^[5]	125.06
90% Confidence Interval	( 105.58 to 148.12 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Natural log-transformed Cmax values were compared between treatments using a linear mixed effects model, with treatment as a fixed effect and patient as a random effect.
[5]	Other relevant estimation information:
	Fexofenadine + AZD9291 multiple dose versus fexofenadine alone.

2. Primary Outcome Measure: Area under plasma concentration-time curve from time zero extrapolated to infinity (AUC) for fexofenadine after dosing alone and in combination with AZD9291 [ Time Frame: Blood samples were collected on Days 1 to 4 in Treatment Period 1, and on Days 1 to 4 and Days 39 to 42 in Treatment Period 2. PK sampling at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 24, 36, 48, 60 and 72 hours post-dose (fexofenadine dosing). ]

Measure Type	Primary
Measure Name	Area under plasma concentration-time curve from time zero extrapolated to infinity (AUC) for fexofenadine after dosing alone and in combination with AZD9291
Measure Description	Rate and extent of absorption of fexofenadine by assessment of AUC following administration of fexofenadine alone (during Treatment Period 1) and then with AZD9291 as a single dose and as multiple doses (during Treatment Period 2).
Time Frame	Blood samples were collected on Days 1 to 4 in Treatment Period 1, and on Days 1 to 4 and Days 39 to 42 in Treatment Period 2. PK sampling at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 24, 36, 48, 60 and 72 hours post-dose (fexofenadine dosing).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose for any analyte without any important deviations or events that would exclude the patient. Only patients with data available at the timepoints of testing were included in the analyses.

Reporting Groups

	Description
Fexofenadine alone (Treatment Period 1)	Patients received a single oral dose of fexofenadine 120 mg on Day 1 of Treatment Period 1.
Fexofenadine + AZD9291 single dose (Treatment Period 2)	Patients received a single oral dose of fexofenadine 120 mg in combination with a single oral dose of AZD9291 80 mg on Day 1 of Treatment Period 2.
Fexofenadine + AZD9291 multiple dose (Treatment Period 2)	Patients received oral doses of AZD9291 80 mg once daily from Days 4 to 41 inclusive during Treatment Period 2. In addition, patients received a single oral dose of fexofenadine 120 mg on Day 39 of Treatment Period 2.

Measured Values

	Fexofenadine alone (Treatment Period 1)	Fexofenadine + AZD9291 single dose (Treatment Period 2)	Fexofenadine + AZD9291 multiple dose (Treatment Period 2)
Number of Participants Analyzed [units:participants]	22	19	20
Area under plasma concentration-time curve from time zero extrapolated to infinity (AUC) for fexofenadine after dosing alone and in combination with AZD9291 [units: ng * hour per mL (ng*h/mL)] Geometric Mean (Geometric Coefficient of Variation)	3291 (56.9%)	5081 (53.1%)	3996 (33.5%)

Statistical Analysis 1 for Area under plasma concentration-time curve from time zero extrapolated to infinity (AUC) for fexofenadine after dosing alone and in combination with AZD9291

Groups^[1]	Fexofenadine alone (Treatment Period 1), Fexofenadine + AZD9291 single dose (Treatment Period 2)
Other^[5]	155.50
90% Confidence Interval	( 135.39 to 178.59 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Natural log-transformed AUC values were compared between treatments using a linear mixed effects model, with treatment as a fixed effect and patient as a random effect.
[5]	Other relevant estimation information:
	Fexofenadine + AZD9291 single dose versus fexofenadine alone.

Statistical Analysis 2 for Area under plasma concentration-time curve from time zero extrapolated to infinity (AUC) for fexofenadine after dosing alone and in combination with AZD9291

Groups^[1]	Fexofenadine alone (Treatment Period 1), Fexofenadine + AZD9291 multiple dose (Treatment Period 2)
Other^[5]	127.31
90% Confidence Interval	( 111.15 to 145.82 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Natural log-transformed AUC values were compared between treatments using a linear mixed effects model, with treatment as a fixed effect and patient as a random effect.
[5]	Other relevant estimation information:
	Fexofenadine + AZD9291 multiple dose versus fexofenadine alone.

3. Secondary Outcome Measure: Time to maximum plasma concentration (tmax) for fexofenadine after dosing alone and in combination with AZD9291 [ Time Frame: Blood samples were collected on Days 1 to 4 in Treatment Period 1, and on Days 1 to 4 and Days 39 to 42 in Treatment Period 2. PK sampling at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 24, 36, 48, 60 and 72 hours post-dose (fexofenadine dosing). ]

Measure Type	Secondary
Measure Name	Time to maximum plasma concentration (tmax) for fexofenadine after dosing alone and in combination with AZD9291
Measure Description	Rate and extent of absorption of fexofenadine by assessment of tmax following administration of fexofenadine alone (during Treatment Period 1) and then with AZD9291 as a single dose and as multiple doses (during Treatment Period 2).
Time Frame	Blood samples were collected on Days 1 to 4 in Treatment Period 1, and on Days 1 to 4 and Days 39 to 42 in Treatment Period 2. PK sampling at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 24, 36, 48, 60 and 72 hours post-dose (fexofenadine dosing).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose for any analyte without any important deviations or events that would exclude the patient. Only patients with data available at the timepoints of testing were included in the analyses.

Reporting Groups

	Description
Fexofenadine alone (Treatment Period 1)	Patients received a single oral dose of fexofenadine 120 mg on Day 1 of Treatment Period 1.
Fexofenadine + AZD9291 single dose (Treatment Period 2)	Patients received a single oral dose of fexofenadine 120 mg in combination with a single oral dose of AZD9291 80 mg on Day 1 of Treatment Period 2.
Fexofenadine + AZD9291 multiple dose (Treatment Period 2)	Patients received oral doses of AZD9291 80 mg once daily from Days 4 to 41 inclusive during Treatment Period 2. In addition, patients received a single oral dose of fexofenadine 120 mg on Day 39 of Treatment Period 2.

Measured Values

	Fexofenadine alone (Treatment Period 1)	Fexofenadine + AZD9291 single dose (Treatment Period 2)	Fexofenadine + AZD9291 multiple dose (Treatment Period 2)
Number of Participants Analyzed [units:participants]	24	22	21
Time to maximum plasma concentration (tmax) for fexofenadine after dosing alone and in combination with AZD9291 [units: Hours] Median (Full Range)	2.00 (0.97 to 8.00)	2.96 (1.08 to 6.02)	2.93 (1.00 to 8.13)

Statistical Analysis 1 for Time to maximum plasma concentration (tmax) for fexofenadine after dosing alone and in combination with AZD9291

Groups^[1]	Fexofenadine alone (Treatment Period 1), Fexofenadine + AZD9291 single dose (Treatment Period 2)
Method^[3]	Other [Wilcoxon signed rank test]
P-Value^[4]	0.0505
Other^[5]	0.48
90% Confidence Interval	( 0.05 to 0.75 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	P-values for treatment difference were calculated using the Wilcoxon signed rank test.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	Hodges-Lehmann median estimator of the difference in treatments for Fexofenadine + AZD9291 single dose versus fexofenadine alone.

Statistical Analysis 2 for Time to maximum plasma concentration (tmax) for fexofenadine after dosing alone and in combination with AZD9291

Groups^[1]	Fexofenadine alone (Treatment Period 1), Fexofenadine + AZD9291 multiple dose (Treatment Period 2)
Method^[3]	Other [Wilcoxon signed rank test]
P-Value^[4]	0.0365
Other^[5]	0.52
90% Confidence Interval	( 0.18 to 1.00 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	P-values for treatment difference were calculated using the Wilcoxon signed rank test.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	Hodges-Lehmann median estimator of the difference in treatments for Fexofenadine + AZD9291 multiple dose versus fexofenadine alone.

4. Secondary Outcome Measure: Area under plasma concentration-time curve from time 0 to the last quantifiable concentration at time “t” (AUC0-t) for fexofenadine after dosing alone and in combination with AZD9291 [ Time Frame: Blood samples were collected on Days 1 to 4 in Treatment Period 1, and on Days 1 to 4 and Days 39 to 42 in Treatment Period 2. PK sampling at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 24, 36, 48, 60 and 72 hours post-dose (fexofenadine dosing). ]

Measure Type	Secondary
Measure Name	Area under plasma concentration-time curve from time 0 to the last quantifiable concentration at time “t” (AUC0-t) for fexofenadine after dosing alone and in combination with AZD9291
Measure Description	Rate and extent of absorption of fexofenadine by assessment of AUC0-t following administration of fexofenadine alone (during Treatment Period 1) and then with AZD9291 as a single dose and as multiple doses (during Treatment Period 2).
Time Frame	Blood samples were collected on Days 1 to 4 in Treatment Period 1, and on Days 1 to 4 and Days 39 to 42 in Treatment Period 2. PK sampling at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 24, 36, 48, 60 and 72 hours post-dose (fexofenadine dosing).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose for any analyte without any important deviations or events that would exclude the patient. Only patients with data available at the timepoints of testing were included in the analyses.

Reporting Groups

	Description
Fexofenadine alone (Treatment Period 1)	Patients received a single oral dose of fexofenadine 120 mg on Day 1 of Treatment Period 1.
Fexofenadine + AZD9291 single dose (Treatment Period 2)	Patients received a single oral dose of fexofenadine 120 mg in combination with a single oral dose of AZD9291 80 mg on Day 1 of Treatment Period 2.
Fexofenadine + AZD9291 multiple dose (Treatment Period 2)	Patients received oral doses of AZD9291 80 mg once daily from Days 4 to 41 inclusive during Treatment Period 2. In addition, patients received a single oral dose of fexofenadine 120 mg on Day 39 of Treatment Period 2.

Measured Values

	Fexofenadine alone (Treatment Period 1)	Fexofenadine + AZD9291 single dose (Treatment Period 2)	Fexofenadine + AZD9291 multiple dose (Treatment Period 2)
Number of Participants Analyzed [units:participants]	24	20	21
Area under plasma concentration-time curve from time 0 to the last quantifiable concentration at time “t” (AUC0-t) for fexofenadine after dosing alone and in combination with AZD9291 [units: ng*h/mL] Geometric Mean (Geometric Coefficient of Variation)	2988 (59.2%)	4813 (54.4%)	3801 (35.3%)

No statistical analysis provided for Area under plasma concentration-time curve from time 0 to the last quantifiable concentration at time “t” (AUC0-t) for fexofenadine after dosing alone and in combination with AZD9291

5. Secondary Outcome Measure: Apparent plasma clearance (CL/F) for fexofenadine after dosing alone and in combination with AZD9291 [ Time Frame: Blood samples were collected on Days 1 to 4 in Treatment Period 1, and on Days 1 to 4 and Days 39 to 42 in Treatment Period 2. PK sampling at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 24, 36, 48, 60 and 72 hours post-dose (fexofenadine dosing). ]

Measure Type	Secondary
Measure Name	Apparent plasma clearance (CL/F) for fexofenadine after dosing alone and in combination with AZD9291
Measure Description	Rate and extent of absorption of fexofenadine by assessment of CL/F following administration of fexofenadine alone (during Treatment Period 1) and then with AZD9291 as a single dose and as multiple doses (during Treatment Period 2).
Time Frame	Blood samples were collected on Days 1 to 4 in Treatment Period 1, and on Days 1 to 4 and Days 39 to 42 in Treatment Period 2. PK sampling at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 24, 36, 48, 60 and 72 hours post-dose (fexofenadine dosing).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose for any analyte without any important deviations or events that would exclude the patient. Only patients with data available at the timepoints of testing were included in the analyses.

Reporting Groups

	Description
Fexofenadine alone (Treatment Period 1)	Patients received a single oral dose of fexofenadine 120 mg on Day 1 of Treatment Period 1.
Fexofenadine + AZD9291 single dose (Treatment Period 2)	Patients received a single oral dose of fexofenadine 120 mg in combination with a single oral dose of AZD9291 80 mg on Day 1 of Treatment Period 2.
Fexofenadine + AZD9291 multiple dose (Treatment Period 2)	Patients received oral doses of AZD9291 80 mg once daily from Days 4 to 41 inclusive during Treatment Period 2. In addition, patients received a single oral dose of fexofenadine 120 mg on Day 39 of Treatment Period 2.

Measured Values

	Fexofenadine alone (Treatment Period 1)	Fexofenadine + AZD9291 single dose (Treatment Period 2)	Fexofenadine + AZD9291 multiple dose (Treatment Period 2)
Number of Participants Analyzed [units:participants]	22	19	20
Apparent plasma clearance (CL/F) for fexofenadine after dosing alone and in combination with AZD9291 [units: Litres per hour (L/h)] Mean (Standard Deviation)	38.64 (19.29)	24.47 (10.66)	29.42 (9.383)

No statistical analysis provided for Apparent plasma clearance (CL/F) for fexofenadine after dosing alone and in combination with AZD9291

6. Secondary Outcome Measure: Apparent volume of distribution (Vz/F) for fexofenadine after dosing alone and in combination with AZD9291 [ Time Frame: Blood samples were collected on Days 1 to 4 in Treatment Period 1, and on Days 1 to 4 and Days 39 to 42 in Treatment Period 2. PK sampling at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 24, 36, 48, 60 and 72 hours post-dose (fexofenadine dosing). ]

Measure Type	Secondary
Measure Name	Apparent volume of distribution (Vz/F) for fexofenadine after dosing alone and in combination with AZD9291
Measure Description	Rate and extent of absorption of fexofenadine by assessment of Vz/F following administration of fexofenadine alone (during Treatment Period 1) and then with AZD9291 as a single dose and as multiple doses (during Treatment Period 2).
Time Frame	Blood samples were collected on Days 1 to 4 in Treatment Period 1, and on Days 1 to 4 and Days 39 to 42 in Treatment Period 2. PK sampling at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 24, 36, 48, 60 and 72 hours post-dose (fexofenadine dosing).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose for any analyte without any important deviations or events that would exclude the patient. Only patients with data available at the timepoints of testing were included in the analyses.

Reporting Groups

	Description
Fexofenadine alone (Treatment Period 1)	Patients received a single oral dose of fexofenadine 120 mg on Day 1 of Treatment Period 1.
Fexofenadine + AZD9291 single dose (Treatment Period 2)	Patients received a single oral dose of fexofenadine 120 mg in combination with a single oral dose of AZD9291 80 mg on Day 1 of Treatment Period 2.
Fexofenadine + AZD9291 multiple dose (Treatment Period 2)	Patients received oral doses of AZD9291 80 mg once daily from Days 4 to 41 inclusive during Treatment Period 2. In addition, patients received a single oral dose of fexofenadine 120 mg on Day 39 of Treatment Period 2.

Measured Values

	Fexofenadine alone (Treatment Period 1)	Fexofenadine + AZD9291 single dose (Treatment Period 2)	Fexofenadine + AZD9291 multiple dose (Treatment Period 2)
Number of Participants Analyzed [units:participants]	22	19	20
Apparent volume of distribution (Vz/F) for fexofenadine after dosing alone and in combination with AZD9291 [units: Litres] Mean (Standard Deviation)	619.4 (342.7)	305.4 (150.0)	349.1 (180.4)

No statistical analysis provided for Apparent volume of distribution (Vz/F) for fexofenadine after dosing alone and in combination with AZD9291

7. Secondary Outcome Measure: Terminal elimination half-life (t1/2[lambda_z]) for fexofenadine after dosing alone and in combination with AZD9291 [ Time Frame: Blood samples were collected on Days 1 to 4 in Treatment Period 1, and on Days 1 to 4 and Days 39 to 42 in Treatment Period 2. PK sampling at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 24, 36, 48, 60 and 72 hours post-dose (fexofenadine dosing). ]

Measure Type	Secondary
Measure Name	Terminal elimination half-life (t1/2[lambda_z]) for fexofenadine after dosing alone and in combination with AZD9291
Measure Description	Rate and extent of absorption of fexofenadine by assessment of t1/2(lambda_z) following administration of fexofenadine alone (during Treatment Period 1) and then with AZD9291 as a single dose and as multiple doses (during Treatment Period 2).
Time Frame	Blood samples were collected on Days 1 to 4 in Treatment Period 1, and on Days 1 to 4 and Days 39 to 42 in Treatment Period 2. PK sampling at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 24, 36, 48, 60 and 72 hours post-dose (fexofenadine dosing).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose for any analyte without any important deviations or events that would exclude the patient. Only patients with data available at the timepoints of testing were included in the analyses.

Reporting Groups

	Description
Fexofenadine alone (Treatment Period 1)	Patients received a single oral dose of fexofenadine 120 mg on Day 1 of Treatment Period 1.
Fexofenadine + AZD9291 single dose (Treatment Period 2)	Patients received a single oral dose of fexofenadine 120 mg in combination with a single oral dose of AZD9291 80 mg on Day 1 of Treatment Period 2.
Fexofenadine + AZD9291 multiple dose (Treatment Period 2)	Patients received oral doses of AZD9291 80 mg once daily from Days 4 to 41 inclusive during Treatment Period 2. In addition, patients received a single oral dose of fexofenadine 120 mg on Day 39 of Treatment Period 2.

Measured Values

	Fexofenadine alone (Treatment Period 1)	Fexofenadine + AZD9291 single dose (Treatment Period 2)	Fexofenadine + AZD9291 multiple dose (Treatment Period 2)
Number of Participants Analyzed [units:participants]	22	19	20
Terminal elimination half-life (t1/2[lambda_z]) for fexofenadine after dosing alone and in combination with AZD9291 [units: Hours] Mean (Standard Deviation)	12.55 (7.608)	9.720 (5.571)	8.682 (4.780)

No statistical analysis provided for Terminal elimination half-life (t1/2[lambda_z]) for fexofenadine after dosing alone and in combination with AZD9291

8. Secondary Outcome Measure: Cmax for AZD9291, and AZ5104 and AZ7550 (metabolites) after a single dose of AZD9291 [ Time Frame: Blood samples were collected on Days 1 to 4 in Treatment Period 2. PK sampling at pre-dose, 1, 2, 3, 4, 6, 8, 10, 24, 36, 48, 60 and 72 hours post-dose (AZD9291 dosing). ]

Measure Type	Secondary
Measure Name	Cmax for AZD9291, and AZ5104 and AZ7550 (metabolites) after a single dose of AZD9291
Measure Description	Rate and extent of absorption of AZD9291, and AZ5104 and AZ7550 (metabolites) by assessment of Cmax following administration of a single dose of AZD9291 in combination with a single dose of fexofenadine in Treatment Period 2.
Time Frame	Blood samples were collected on Days 1 to 4 in Treatment Period 2. PK sampling at pre-dose, 1, 2, 3, 4, 6, 8, 10, 24, 36, 48, 60 and 72 hours post-dose (AZD9291 dosing).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose for any analyte without any important deviations or events that would exclude the patient. Only patients with data available at the timepoints of testing were included in the analyses.

Reporting Groups

	Description
Fexofenadine + AZD9291 single dose (Treatment Period 2)	Patients received a single oral dose of fexofenadine 120 mg in combination with a single oral dose of AZD9291 80 mg on Day 1 of Treatment Period 2.

Measured Values

	Fexofenadine + AZD9291 single dose (Treatment Period 2)
Number of Participants Analyzed [units:participants]	24
Cmax for AZD9291, and AZ5104 and AZ7550 (metabolites) after a single dose of AZD9291 [units: Nanomolar (nM)] Geometric Mean (Geometric Coefficient of Variation)
AZD9291	221.8 (70.8%)
AZ5104	8.509 (61.4%)
AZ7550	4.621 (59.9%)

No statistical analysis provided for Cmax for AZD9291, and AZ5104 and AZ7550 (metabolites) after a single dose of AZD9291

9. Secondary Outcome Measure: Area under plasma concentration-time curve from time zero to 24 hours (AUC0-24) for AZD9291, and AZ5104 and AZ7550 (metabolites) after a single dose of AZD9291 [ Time Frame: Blood samples were collected on Days 1 to 4 in Treatment Period 2. PK sampling at pre-dose, 1, 2, 3, 4, 6, 8, 10, 24, 36, 48, 60 and 72 hours post-dose (AZD9291 dosing). ]

Measure Type	Secondary
Measure Name	Area under plasma concentration-time curve from time zero to 24 hours (AUC0-24) for AZD9291, and AZ5104 and AZ7550 (metabolites) after a single dose of AZD9291
Measure Description	Rate and extent of absorption of AZD9291, and AZ5104 and AZ7550 (metabolites) by assessment of AUC0-24 following administration of a single dose of AZD9291 in combination with a single dose of fexofenadine in Treatment Period 2.
Time Frame	Blood samples were collected on Days 1 to 4 in Treatment Period 2. PK sampling at pre-dose, 1, 2, 3, 4, 6, 8, 10, 24, 36, 48, 60 and 72 hours post-dose (AZD9291 dosing).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose for any analyte without any important deviations or events that would exclude the patient. Only patients with data available at the timepoints of testing were included in the analyses.

Reporting Groups

	Description
Fexofenadine + AZD9291 single dose (Treatment Period 2)	Patients received a single oral dose of fexofenadine 120 mg in combination with a single oral dose of AZD9291 80 mg on Day 1 of Treatment Period 2.

Measured Values

	Fexofenadine + AZD9291 single dose (Treatment Period 2)
Number of Participants Analyzed [units:participants]	24
Area under plasma concentration-time curve from time zero to 24 hours (AUC0-24) for AZD9291, and AZ5104 and AZ7550 (metabolites) after a single dose of AZD9291 [units: nM*h] Geometric Mean (Geometric Coefficient of Variation)
AZD9291	3364 (54.5%)
AZ5104	149.3 (64.1%)
AZ7550	76.26 (66.3%)

No statistical analysis provided for Area under plasma concentration-time curve from time zero to 24 hours (AUC0-24) for AZD9291, and AZ5104 and AZ7550 (metabolites) after a single dose of AZD9291

10. Secondary Outcome Measure: Area under the plasma concentration-time curve from time zero to 72 hours (AUC0-72) for AZD9291, and AZ5104 and AZ7550 (metabolites) after a single dose of AZD9291 [ Time Frame: Blood samples were collected on Days 1 to 4 in Treatment Period 2. PK sampling at pre-dose, 1, 2, 3, 4, 6, 8, 10, 24, 36, 48, 60 and 72 hours post-dose (AZD9291 dosing). ]

Measure Type	Secondary
Measure Name	Area under the plasma concentration-time curve from time zero to 72 hours (AUC0-72) for AZD9291, and AZ5104 and AZ7550 (metabolites) after a single dose of AZD9291
Measure Description	Rate and extent of absorption of AZD9291, and AZ5104 and AZ7550 (metabolites) by assessment of AUC0-72 following administration of a single dose of AZD9291 in combination with a single dose of fexofenadine in Treatment Period 2.
Time Frame	Blood samples were collected on Days 1 to 4 in Treatment Period 2. PK sampling at pre-dose, 1, 2, 3, 4, 6, 8, 10, 24, 36, 48, 60 and 72 hours post-dose (AZD9291 dosing).
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose for any analyte without any important deviations or events that would exclude the patient. Only patients with data available at the timepoints of testing were included in the analyses.

Reporting Groups

	Description
Fexofenadine + AZD9291 single dose (Treatment Period 2)	Patients received a single oral dose of fexofenadine 120 mg in combination with a single oral dose of AZD9291 80 mg on Day 1 of Treatment Period 2.

Measured Values

	Fexofenadine + AZD9291 single dose (Treatment Period 2)
Number of Participants Analyzed [units:participants]	21
Area under the plasma concentration-time curve from time zero to 72 hours (AUC0-72) for AZD9291, and AZ5104 and AZ7550 (metabolites) after a single dose of AZD9291 [units: nM*h] Geometric Mean (Geometric Coefficient of Variation)
AZD9291	7354 (42.9%)
AZ5104	473.1 (62.1%)
AZ7550	255.9 (61.3%)

No statistical analysis provided for Area under the plasma concentration-time curve from time zero to 72 hours (AUC0-72) for AZD9291, and AZ5104 and AZ7550 (metabolites) after a single dose of AZD9291

11. Secondary Outcome Measure: Tmax for AZD9291, and AZ5104 and AZ7550 (metabolites) after a single dose of AZD9291 [ Time Frame: Blood samples were collected on Days 1 to 4 in Treatment Period 2. PK sampling at pre-dose, 1, 2, 3, 4, 6, 8, 10, 24, 36, 48, 60 and 72 hours post-dose (AZD9291 dosing). ]

Measure Type	Secondary
Measure Name	Tmax for AZD9291, and AZ5104 and AZ7550 (metabolites) after a single dose of AZD9291
Measure Description	Rate and extent of absorption of AZD9291, and AZ5104 and AZ7550 (metabolites) by assessment of tmax following administration of a single dose of AZD9291 in combination with a single dose of fexofenadine in Treatment Period 2.
Time Frame	Blood samples were collected on Days 1 to 4 in Treatment Period 2. PK sampling at pre-dose, 1, 2, 3, 4, 6, 8, 10, 24, 36, 48, 60 and 72 hours post-dose (AZD9291 dosing).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose for any analyte without any important deviations or events that would exclude the patient. Only patients with data available at the timepoints of testing were included in the analyses.

Reporting Groups

	Description
Fexofenadine + AZD9291 single dose (Treatment Period 2)	Patients received a single oral dose of fexofenadine 120 mg in combination with a single oral dose of AZD9291 80 mg on Day 1 of Treatment Period 2.

Measured Values

	Fexofenadine + AZD9291 single dose (Treatment Period 2)
Number of Participants Analyzed [units:participants]	24
Tmax for AZD9291, and AZ5104 and AZ7550 (metabolites) after a single dose of AZD9291 [units: Hours] Median (Full Range)
AZD9291	7.96 (2.92 to 59.33)
AZ5104	24.00 (4.00 to 72.08)
AZ7550	24.52 (4.00 to 73.00)

No statistical analysis provided for Tmax for AZD9291, and AZ5104 and AZ7550 (metabolites) after a single dose of AZD9291

12. Secondary Outcome Measure: Metabolite to parent ratios of Cmax (MRCmax) for AZ5104 and AZ7550 after a single dose of AZD9291 [ Time Frame: Blood samples were collected on Days 1 to 4 in Treatment Period 2. PK sampling at pre-dose, 1, 2, 3, 4, 6, 8, 10, 24, 36, 48, 60 and 72 hours post-dose (AZD9291 dosing). ]

Measure Type	Secondary
Measure Name	Metabolite to parent ratios of Cmax (MRCmax) for AZ5104 and AZ7550 after a single dose of AZD9291
Measure Description	Assessment of MRCmax for each metabolite following administration of a single dose of AZD9291 in combination with a single dose of fexofenadine in Treatment Period 2. Ratios were calculated for AZ5104 to AZD9291 and for AZ7550 to AZD9291.
Time Frame	Blood samples were collected on Days 1 to 4 in Treatment Period 2. PK sampling at pre-dose, 1, 2, 3, 4, 6, 8, 10, 24, 36, 48, 60 and 72 hours post-dose (AZD9291 dosing).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose for any analyte without any important deviations or events that would exclude the patient. Only patients with data available at the timepoints of testing were included in the analyses.

Reporting Groups

	Description
Fexofenadine + AZD9291 single dose (Treatment Period 2)	Patients received a single oral dose of fexofenadine 120 mg in combination with a single oral dose of AZD9291 80 mg on Day 1 of Treatment Period 2.

Measured Values

	Fexofenadine + AZD9291 single dose (Treatment Period 2)
Number of Participants Analyzed [units:participants]	21
Metabolite to parent ratios of Cmax (MRCmax) for AZ5104 and AZ7550 after a single dose of AZD9291 [units: Ratio] Geometric Mean (Geometric Coefficient of Variation)
AZ5104 to AZD9291	0.04439 (35.6%)
AZ7550 to AZD9291	0.02410 (38.8%)

No statistical analysis provided for Metabolite to parent ratios of Cmax (MRCmax) for AZ5104 and AZ7550 after a single dose of AZD9291

13. Secondary Outcome Measure: Maximum plasma concentration at steady state (Css,max) for AZD9291, and AZ5104 and AZ7550 (metabolites) after multiple doses of AZD9291 [ Time Frame: Blood samples were collected on Days 11, 18, 25 and 32 in Treatment Period 2 at pre-dose, and on Days 39 and 40 in Treatment Period 2 at pre-dose, 1, 2, 3, 4, 6, 8, 10 and 24 hours post-dose (AZD9291 dosing). ]

Measure Type	Secondary
Measure Name	Maximum plasma concentration at steady state (Css,max) for AZD9291, and AZ5104 and AZ7550 (metabolites) after multiple doses of AZD9291
Measure Description	Rate and extent of absorption of AZD9291, and AZ5104 and AZ7550 (metabolites) by assessment of Css,max following administration of multiple doses of AZD9291 in combination with fexofenadine as a single dose during Treatment Period 2.
Time Frame	Blood samples were collected on Days 11, 18, 25 and 32 in Treatment Period 2 at pre-dose, and on Days 39 and 40 in Treatment Period 2 at pre-dose, 1, 2, 3, 4, 6, 8, 10 and 24 hours post-dose (AZD9291 dosing).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose for any analyte without any important deviations or events that would exclude the patient. Only patients with data available at the timepoints of testing were included in the analyses.

Reporting Groups

	Description
Fexofenadine + AZD9291 multiple dose (Treatment Period 2)	Patients received oral doses of AZD9291 80 mg once daily from Days 4 to 41 inclusive during Treatment Period 2. In addition, patients received a single oral dose of fexofenadine 120 mg on Day 39 of Treatment Period 2.

Measured Values

	Fexofenadine + AZD9291 multiple dose (Treatment Period 2)
Number of Participants Analyzed [units:participants]	21
Maximum plasma concentration at steady state (Css,max) for AZD9291, and AZ5104 and AZ7550 (metabolites) after multiple doses of AZD9291 [units: nM] Geometric Mean (Geometric Coefficient of Variation)
AZD9291	643.2 (27.4%)
AZ5104	63.11 (36.9%)
AZ7550	57.86 (39.0%)

No statistical analysis provided for Maximum plasma concentration at steady state (Css,max) for AZD9291, and AZ5104 and AZ7550 (metabolites) after multiple doses of AZD9291

14. Secondary Outcome Measure: Area under plasma concentration-time curve during the dosing interval (AUCtau) for AZD9291, and AZ5104 and AZ7550 (metabolites) after multiple doses of AZD9291 [ Time Frame: Blood samples were collected on Days 11, 18, 25 and 32 in Treatment Period 2 at pre-dose, and on Days 39 and 40 in Treatment Period 2 at pre-dose, 1, 2, 3, 4, 6, 8, 10 and 24 hours post-dose (AZD9291 dosing). ]

Measure Type	Secondary
Measure Name	Area under plasma concentration-time curve during the dosing interval (AUCtau) for AZD9291, and AZ5104 and AZ7550 (metabolites) after multiple doses of AZD9291
Measure Description	Rate and extent of absorption of AZD9291, and AZ5104 and AZ7550 (metabolites) by assessment of AUCtau following administration of multiple doses of AZD9291 in combination with fexofenadine as a single dose during Treatment Period 2.
Time Frame	Blood samples were collected on Days 11, 18, 25 and 32 in Treatment Period 2 at pre-dose, and on Days 39 and 40 in Treatment Period 2 at pre-dose, 1, 2, 3, 4, 6, 8, 10 and 24 hours post-dose (AZD9291 dosing).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose for any analyte without any important deviations or events that would exclude the patient. Only patients with data available at the timepoints of testing were included in the analyses.

Reporting Groups

	Description
Fexofenadine + AZD9291 multiple dose (Treatment Period 2)	Patients received oral doses of AZD9291 80 mg once daily from Days 4 to 41 inclusive during Treatment Period 2. In addition, patients received a single oral dose of fexofenadine 120 mg on Day 39 of Treatment Period 2.

Measured Values

	Fexofenadine + AZD9291 multiple dose (Treatment Period 2)
Number of Participants Analyzed [units:participants]	21
Area under plasma concentration-time curve during the dosing interval (AUCtau) for AZD9291, and AZ5104 and AZ7550 (metabolites) after multiple doses of AZD9291 [units: nM*h] Geometric Mean (Geometric Coefficient of Variation)
AZD9291	11910 (30.4%)
AZ5104	1281 (36.0%)
AZ7550	1199 (38.7%)

No statistical analysis provided for Area under plasma concentration-time curve during the dosing interval (AUCtau) for AZD9291, and AZ5104 and AZ7550 (metabolites) after multiple doses of AZD9291

15. Secondary Outcome Measure: Minimum plasma concentration at steady state (Css,min) for AZD9291, and AZ5104 and AZ7550 (metabolites) after multiple doses of AZD9291 [ Time Frame: Blood samples were collected on Days 11, 18, 25 and 32 in Treatment Period 2 at pre-dose, and on Days 39 and 40 in Treatment Period 2 at pre-dose, 1, 2, 3, 4, 6, 8, 10 and 24 hours post-dose (AZD9291 dosing). ]

Measure Type	Secondary
Measure Name	Minimum plasma concentration at steady state (Css,min) for AZD9291, and AZ5104 and AZ7550 (metabolites) after multiple doses of AZD9291
Measure Description	Rate and extent of absorption of AZD9291, and AZ5104 and AZ7550 (metabolites) by assessment of Css,min following administration of multiple doses of AZD9291 in combination with fexofenadine as a single dose during Treatment Period 2.
Time Frame	Blood samples were collected on Days 11, 18, 25 and 32 in Treatment Period 2 at pre-dose, and on Days 39 and 40 in Treatment Period 2 at pre-dose, 1, 2, 3, 4, 6, 8, 10 and 24 hours post-dose (AZD9291 dosing).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose for any analyte without any important deviations or events that would exclude the patient. Only patients with data available at the timepoints of testing were included in the analyses.

Reporting Groups

	Description
Fexofenadine + AZD9291 multiple dose (Treatment Period 2)	Patients received oral doses of AZD9291 80 mg once daily from Days 4 to 41 inclusive during Treatment Period 2. In addition, patients received a single oral dose of fexofenadine 120 mg on Day 39 of Treatment Period 2.

Measured Values

	Fexofenadine + AZD9291 multiple dose (Treatment Period 2)
Number of Participants Analyzed [units:participants]	21
Minimum plasma concentration at steady state (Css,min) for AZD9291, and AZ5104 and AZ7550 (metabolites) after multiple doses of AZD9291 [units: nM] Geometric Mean (Geometric Coefficient of Variation)
AZD9291	364.9 (38.8%)
AZ5104	43.52 (41.7%)
AZ7550	40.68 (44.1%)

No statistical analysis provided for Minimum plasma concentration at steady state (Css,min) for AZD9291, and AZ5104 and AZ7550 (metabolites) after multiple doses of AZD9291

16. Secondary Outcome Measure: Time to maximum plasma concentration at steady state (tss,max) for AZD9291, and AZ5104 and AZ7550 (metabolites) after multiple doses of AZD9291 [ Time Frame: Blood samples were collected on Days 11, 18, 25 and 32 in Treatment Period 2 at pre-dose, and on Days 39 and 40 in Treatment Period 2 at pre-dose, 1, 2, 3, 4, 6, 8, 10 and 24 hours post-dose (AZD9291 dosing). ]

Measure Type	Secondary
Measure Name	Time to maximum plasma concentration at steady state (tss,max) for AZD9291, and AZ5104 and AZ7550 (metabolites) after multiple doses of AZD9291
Measure Description	Rate and extent of absorption of AZD9291, and AZ5104 and AZ7550 (metabolites) by assessment of tss,max following administration of multiple doses of AZD9291 in combination with fexofenadine as a single dose during Treatment Period 2.
Time Frame	Blood samples were collected on Days 11, 18, 25 and 32 in Treatment Period 2 at pre-dose, and on Days 39 and 40 in Treatment Period 2 at pre-dose, 1, 2, 3, 4, 6, 8, 10 and 24 hours post-dose (AZD9291 dosing).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose for any analyte without any important deviations or events that would exclude the patient. Only patients with data available at the timepoints of testing were included in the analyses.

Reporting Groups

	Description
Fexofenadine + AZD9291 multiple dose (Treatment Period 2)	Patients received oral doses of AZD9291 80 mg once daily from Days 4 to 41 inclusive during Treatment Period 2. In addition, patients received a single oral dose of fexofenadine 120 mg on Day 39 of Treatment Period 2.

Measured Values

	Fexofenadine + AZD9291 multiple dose (Treatment Period 2)
Number of Participants Analyzed [units:participants]	21
Time to maximum plasma concentration at steady state (tss,max) for AZD9291, and AZ5104 and AZ7550 (metabolites) after multiple doses of AZD9291 [units: Hours] Median (Full Range)
AZD9291	4.03 (0.00 to 10.12)
AZ5104	6.00 (0.00 to 10.03)
AZ7550	7.92 (0.00 to 10.12)

No statistical analysis provided for Time to maximum plasma concentration at steady state (tss,max) for AZD9291, and AZ5104 and AZ7550 (metabolites) after multiple doses of AZD9291

17. Secondary Outcome Measure: Metabolite to parent ratios of Css,max (MRCss,max) for AZ5104 and AZ7550 after multiple doses of AZD9291 [ Time Frame: Blood samples were collected on Days 11, 18, 25 and 32 in Treatment Period 2 at pre-dose, and on Days 39 and 40 in Treatment Period 2 at pre-dose, 1, 2, 3, 4, 6, 8, 10 and 24 hours post-dose (AZD9291 dosing). ]

Measure Type	Secondary
Measure Name	Metabolite to parent ratios of Css,max (MRCss,max) for AZ5104 and AZ7550 after multiple doses of AZD9291
Measure Description	Assessment of MRCss,max for each metabolite following administration of multiple doses of AZD9291 in combination with fexofenadine as a single dose during Treatment Period 2. Ratios were calculated for AZ5104 to AZD9291 and for AZ7550 to AZD9291.
Time Frame	Blood samples were collected on Days 11, 18, 25 and 32 in Treatment Period 2 at pre-dose, and on Days 39 and 40 in Treatment Period 2 at pre-dose, 1, 2, 3, 4, 6, 8, 10 and 24 hours post-dose (AZD9291 dosing).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose for any analyte without any important deviations or events that would exclude the patient. Only patients with data available at the timepoints of testing were included in the analyses.

Reporting Groups

	Description
Fexofenadine + AZD9291 multiple dose (Treatment Period 2)	Patients received oral doses of AZD9291 80 mg once daily from Days 4 to 41 inclusive during Treatment Period 2. In addition, patients received a single oral dose of fexofenadine 120 mg on Day 39 of Treatment Period 2.

Measured Values

	Fexofenadine + AZD9291 multiple dose (Treatment Period 2)
Number of Participants Analyzed [units:participants]	21
Metabolite to parent ratios of Css,max (MRCss,max) for AZ5104 and AZ7550 after multiple doses of AZD9291 [units: Ratio] Geometric Mean (Geometric Coefficient of Variation)
AZ5104	0.09812 (28.4%)
AZ7550	0.08996 (50.0%)

No statistical analysis provided for Metabolite to parent ratios of Css,max (MRCss,max) for AZ5104 and AZ7550 after multiple doses of AZD9291

18. Secondary Outcome Measure: Metabolite to parent ratios of AUCtau (MRAUCtau) for AZ5104 and AZ7550 after multiple doses of AZD9291 [ Time Frame: Blood samples were collected on Days 11, 18, 25 and 32 in Treatment Period 2 at pre-dose, and on Days 39 and 40 in Treatment Period 2 at pre-dose, 1, 2, 3, 4, 6, 8, 10 and 24 hours post-dose (AZD9291 dosing). ]

Measure Type	Secondary
Measure Name	Metabolite to parent ratios of AUCtau (MRAUCtau) for AZ5104 and AZ7550 after multiple doses of AZD9291
Measure Description	Assessment of MRAUCtau for each metabolite following administration of multiple doses of AZD9291 in combination with fexofenadine as a single dose during Treatment Period 2. Ratios were calculated for AZ5104 to AZD9291 and for AZ7550 to AZD9291.
Time Frame	Blood samples were collected on Days 11, 18, 25 and 32 in Treatment Period 2 at pre-dose, and on Days 39 and 40 in Treatment Period 2 at pre-dose, 1, 2, 3, 4, 6, 8, 10 and 24 hours post-dose (AZD9291 dosing).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose for any analyte without any important deviations or events that would exclude the patient. Only patients with data available at the timepoints of testing were included in the analyses.

Reporting Groups

	Description
Fexofenadine + AZD9291 multiple dose (Treatment Period 2)	Patients received oral doses of AZD9291 80 mg once daily from Days 4 to 41 inclusive during Treatment Period 2. In addition, patients received a single oral dose of fexofenadine 120 mg on Day 39 of Treatment Period 2.

Measured Values

	Fexofenadine + AZD9291 multiple dose (Treatment Period 2)
Number of Participants Analyzed [units:participants]	21
Metabolite to parent ratios of AUCtau (MRAUCtau) for AZ5104 and AZ7550 after multiple doses of AZD9291 [units: Ratio] Geometric Mean (Geometric Coefficient of Variation)
AZ5104	0.1075 (29.8%)
AZ7550	0.1007 (53.2%)

No statistical analysis provided for Metabolite to parent ratios of AUCtau (MRAUCtau) for AZ5104 and AZ7550 after multiple doses of AZD9291

19. Secondary Outcome Measure: Accumulation ratio of Css,max (RCss,max) for AZD9291, and AZ5104 and AZ7550 (metabolites) after multiple doses of AZD9291 [ Time Frame: Blood samples were collected on Days 11, 18, 25 and 32 in Treatment Period 2 at pre-dose, and on Days 39 and 40 in Treatment Period 2 at pre-dose, 1, 2, 3, 4, 6, 8, 10 and 24 hours post-dose (AZD9291 dosing). ]

Measure Type	Secondary
Measure Name	Accumulation ratio of Css,max (RCss,max) for AZD9291, and AZ5104 and AZ7550 (metabolites) after multiple doses of AZD9291
Measure Description	Assessment of RCss,max for AZD9291, and AZ5104 and AZ7550 (metabolites) following administration of multiple doses of AZD9291 in combination with fexofenadine as a single dose during Treatment Period 2.
Time Frame	Blood samples were collected on Days 11, 18, 25 and 32 in Treatment Period 2 at pre-dose, and on Days 39 and 40 in Treatment Period 2 at pre-dose, 1, 2, 3, 4, 6, 8, 10 and 24 hours post-dose (AZD9291 dosing).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose for any analyte without any important deviations or events that would exclude the patient. Only patients with data available at the timepoints of testing were included in the analyses.

Reporting Groups

	Description
Fexofenadine + AZD9291 multiple dose (Treatment Period 2)	Patients received oral doses of AZD9291 80 mg once daily from Days 4 to 41 inclusive during Treatment Period 2. In addition, patients received a single oral dose of fexofenadine 120 mg on Day 39 of Treatment Period 2.

Measured Values

	Fexofenadine + AZD9291 multiple dose (Treatment Period 2)
Number of Participants Analyzed [units:participants]	21
Accumulation ratio of Css,max (RCss,max) for AZD9291, and AZ5104 and AZ7550 (metabolites) after multiple doses of AZD9291 [units: Ratio] Geometric Mean (Geometric Coefficient of Variation)
AZD9291	3.159 (68.0%)
AZ5104	7.680 (58.4%)
AZ7550	13.28 (45.0%)

No statistical analysis provided for Accumulation ratio of Css,max (RCss,max) for AZD9291, and AZ5104 and AZ7550 (metabolites) after multiple doses of AZD9291

20. Secondary Outcome Measure: Accumulation ratio for AUCtau (RAUCtau) for AZD9291, and AZ5104 and AZ7550 (metabolites) after multiple doses of AZD9291 [ Time Frame: Blood samples were collected on Days 11, 18, 25 and 32 in Treatment Period 2 at pre-dose, and on Days 39 and 40 in Treatment Period 2 at pre-dose, 1, 2, 3, 4, 6, 8, 10 and 24 hours post-dose (AZD9291 dosing). ]

Measure Type	Secondary
Measure Name	Accumulation ratio for AUCtau (RAUCtau) for AZD9291, and AZ5104 and AZ7550 (metabolites) after multiple doses of AZD9291
Measure Description	Assessment of RAUCtau for AZD9291, and AZ5104 and AZ7550 (metabolites) following administration of multiple doses of AZD9291 in combination with fexofenadine as a single dose during Treatment Period 2.
Time Frame	Blood samples were collected on Days 11, 18, 25 and 32 in Treatment Period 2 at pre-dose, and on Days 39 and 40 in Treatment Period 2 at pre-dose, 1, 2, 3, 4, 6, 8, 10 and 24 hours post-dose (AZD9291 dosing).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose for any analyte without any important deviations or events that would exclude the patient. Only patients with data available at the timepoints of testing were included in the analyses.

Reporting Groups

	Description
Fexofenadine + AZD9291 multiple dose (Treatment Period 2)	Patients received oral doses of AZD9291 80 mg once daily from Days 4 to 41 inclusive during Treatment Period 2. In addition, patients received a single oral dose of fexofenadine 120 mg on Day 39 of Treatment Period 2.

Measured Values

	Fexofenadine + AZD9291 multiple dose (Treatment Period 2)
Number of Participants Analyzed [units:participants]	21
Accumulation ratio for AUCtau (RAUCtau) for AZD9291, and AZ5104 and AZ7550 (metabolites) after multiple doses of AZD9291 [units: Ratio] Geometric Mean (Geometric Coefficient of Variation)
AZD9291	3.858 (60.2%)
AZ5104	9.034 (65.1%)
AZ7550	16.58 (51.3%)

No statistical analysis provided for Accumulation ratio for AUCtau (RAUCtau) for AZD9291, and AZ5104 and AZ7550 (metabolites) after multiple doses of AZD9291

21. Secondary Outcome Measure: Apparent plasma clearance at steady state (CLss/F) for AZD9291 after multiple dosing [ Time Frame: Blood samples were collected on Days 11, 18, 25 and 32 in Treatment Period 2 at pre-dose, and on Days 39 and 40 in Treatment Period 2 at pre-dose, 1, 2, 3, 4, 6, 8, 10 and 24 hours post-dose (AZD9291 dosing). ]

Measure Type	Secondary
Measure Name	Apparent plasma clearance at steady state (CLss/F) for AZD9291 after multiple dosing
Measure Description	Assessment of CLss/F for AZD9291 following administration of multiple doses of AZD9291 in combination with fexofenadine as a single dose during Treatment Period 2.
Time Frame	Blood samples were collected on Days 11, 18, 25 and 32 in Treatment Period 2 at pre-dose, and on Days 39 and 40 in Treatment Period 2 at pre-dose, 1, 2, 3, 4, 6, 8, 10 and 24 hours post-dose (AZD9291 dosing).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose for any analyte without any important deviations or events that would exclude the patient. Only patients with data available at the timepoints of testing were included in the analyses.

Reporting Groups

	Description
Fexofenadine + AZD9291 multiple dose (Treatment Period 2)	Patients received oral doses of AZD9291 80 mg once daily from Days 4 to 41 inclusive during Treatment Period 2. In addition, patients received a single oral dose of fexofenadine 120 mg on Day 39 of Treatment Period 2.

Measured Values

	Fexofenadine + AZD9291 multiple dose (Treatment Period 2)
Number of Participants Analyzed [units:participants]	21
Apparent plasma clearance at steady state (CLss/F) for AZD9291 after multiple dosing [units: L/h] Mean (Standard Deviation)	14.00 (4.055)

No statistical analysis provided for Apparent plasma clearance at steady state (CLss/F) for AZD9291 after multiple dosing

Serious Adverse Events

Time Frame	Up to approximately 5 weeks for Treatment Period 1 (4 days study treatment + 30 days follow up); up to approximately 10 weeks for Treatment Period 2 (41 days study treatment + 30 days follow up).
Additional Description	Treatment Period 1: Adverse events (AEs) collected from day of first dose until day prior to first dose in Treatment Period 2, or until 30 days after last dose if discontinued in Treatment Period 1. Treatment Period 2: AEs collected from day of first dose in Treatment Period 2 until 30 days after last dose, or until last dose in Treatment Period 2 for those entering continued access phase (CAP).

Reporting Groups

Description

Fexofenadine alone (Treatment Period 1)

Patients received a single oral dose of fexofenadine 120 mg on Day 1 of Treatment Period 1.

Fexofenadine + AZD9291 (Treatment Period 2)

Patients received a single oral dose of fexofenadine 120 mg in combination with a single oral dose of AZD9291 80 mg on Day 1 of Treatment Period 2. Patients then received AZD9291 80 mg once daily from Day 4 to Day 41 inclusive. In addition, patients received another single oral dose of fexofenadine 120 mg on Day 39. Thus, patients received sequential treatments of AZD9291 + fexofenadine, followed by AZD9291 alone, followed by AZD9291 + fexofenadine during Treatment Period 2.

Serious Adverse Events

Fexofenadine alone (Treatment Period 1)

Fexofenadine + AZD9291 (Treatment Period 2)

Total, serious adverse events

# participants affected / at risk

0/24 (0.00%)

2/24 (8.33%)

Infections and infestations

Lower respiratory tract infection¹,^†

# participants affected / at risk

0/24 (0.00%)

1/24 (4.17%)

# events

Infections and infestations

Post procedural infection¹,^†

# participants affected / at risk

0/24 (0.00%)

1/24 (4.17%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 20.0

Other Adverse Events

Time Frame	Up to approximately 5 weeks for Treatment Period 1 (4 days study treatment + 30 days follow up); up to approximately 10 weeks for Treatment Period 2 (41 days study treatment + 30 days follow up).
Additional Description	Treatment Period 1: Adverse events (AEs) collected from day of first dose until day prior to first dose in Treatment Period 2, or until 30 days after last dose if discontinued in Treatment Period 1. Treatment Period 2: AEs collected from day of first dose in Treatment Period 2 until 30 days after last dose, or until last dose in Treatment Period 2 for those entering continued access phase (CAP).

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

Description

Fexofenadine alone (Treatment Period 1)

Patients received a single oral dose of fexofenadine 120 mg on Day 1 of Treatment Period 1.

Fexofenadine + AZD9291 (Treatment Period 2)

Other Adverse Events

Fexofenadine alone (Treatment Period 1)

Fexofenadine + AZD9291 (Treatment Period 2)

Total, other (not including serious) adverse events

# participants affected / at risk

0/24 (0.00%)

17/24 (70.83%)

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

0/24 (0.00%)

3/24 (12.50%)

# events

Gastrointestinal disorders

Stomatitis¹,^†

# participants affected / at risk

0/24 (0.00%)

3/24 (12.50%)

# events

Gastrointestinal disorders

Dyspepsia¹,^†

# participants affected / at risk

0/24 (0.00%)

2/24 (8.33%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

0/24 (0.00%)

2/24 (8.33%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

0/24 (0.00%)

2/24 (8.33%)

# events

Skin and subcutaneous tissue disorders

Rash macular¹,^†

# participants affected / at risk

0/24 (0.00%)

2/24 (8.33%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal pain¹,^†

# participants affected / at risk

0/24 (0.00%)

2/24 (8.33%)

# events

General disorders

Asthenia¹,^†

# participants affected / at risk

0/24 (0.00%)

2/24 (8.33%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 20.0

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: The Investigator shall provide the Sponsor with copies of any materials intended for publication, submission or presentation, at least 30 days in advance. At request of the Sponsor, the Investigator shall not include in or shall remove from any proposed publication any Confidential Information, errors or inaccuracies; and shall withhold publication or presentation for a period of 90 days to allow the Sponsor to preserve its proprietary rights and/or protect its Confidential Information.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
At end of the PK phase (i.e. end of Treatment Period 2), the CAP allowed patients to continue receiving AZD9291 if still deriving clinical benefit. No clinical data was databased during the CAP; thus AE data is presented to end of the PK phase only.

Results Point of Contact

Name/Title:	Global Clinical Lead
Organization:	AstraZeneca
Phone	+441625231825
E-mail:	[email protected]

Documents available

Redacted CSP
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Emiliano C Aller

Centro Integral Oncologico Clara Campal

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Redacted CSP

Trial Results Summaries