Study to assess the effect of rifampicin on blood levels and safety of AZD9291, in patients with EGFRm+ NSCLC

Study identifier:D5160C00013

ClinicalTrials.gov identifier:NCT02197247

EudraCT identifier:2014-001525-32

CTIS identifier:N/A

Study Complete

Official Title

A Phase I, Open-Label, Non-Randomised, Multicentre Study to Assess the Effect of Rifampicin (a CYP3A4 Inducer) on the Pharmacokinetics of AZD9291 in Patients with EGFRm Positive NSCLC whose disease has Progressed on an EGFR TKI

Medical condition

Non Small Cell Lung Cancer

Phase

Phase 1

Healthy volunteers

Study drug

Rifampicin, AZD9291 tablet dosing

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 04 Dec 2014

Primary Completion Date: 09 Jul 2015

Study Completion Date: 26 May 2021

Study design

Allocation: N/A
Endpoint Classification: Pharmacokinetics Study
Intervention Model: -
Masking: Open Label
Primary Purpose: Other

Verification:

Verified 01 Jul 2022 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Seoul, Republic of Korea, 03722

Location

Research Site

Seoul, Republic of Korea, 06351

Location

Research Site

Seongnam-si, Republic of Korea, 13620

Location

Research Site

Sevilla, Spain, 41013

Location

Research Site

Madrid, Spain, 28041

Location

Research Site

MAASTRICHT, Netherlands, 6229 HX

Location

Research Site

Amsterdam, Netherlands, 1066 CX

Location

Research Site

L'Hospitalet de Llobregat, Spain, 08908

Arms	Assigned Interventions
Experimental: Rifampicin and AZD9291 Sequential treatments of AZD9291 alone followed by AZD9291 +rifampicin, followed by AZD9291 alone.	Procedure/Surgery: Pharmacokinetic sampling - AZD9291 Blood sampling to measure AZD9291 Drug: Rifampicin Rifampicin (CYP inducer) 600mg taken once daily from Day 29 to Day 49 (Part A) Drug: AZD9291 tablet dosing Part A: AZD9291 80mg tablet taken daily from Days 1 to 77. Part B: AZD9291 80mg tablet taken daily for 12 months. Procedure/Surgery: Pharmacokinetic sampling - rifampicin Blood sampling to measure rifampicin levels Procedure/Surgery: Pharmacokinetic sampling - AZ5140 and AZ7550 Blood samples to measure levels of AZ5140 and AZ7550

Arms

Assigned Interventions

Experimental: Rifampicin and AZD9291
Sequential treatments of AZD9291 alone followed by AZD9291 +rifampicin, followed by AZD9291 alone.

Procedure/Surgery: Pharmacokinetic sampling - AZD9291
Blood sampling to measure AZD9291

Drug: Rifampicin
Rifampicin (CYP inducer) 600mg taken once daily from Day 29 to Day 49 (Part A)

Drug: AZD9291 tablet dosing
Part A: AZD9291 80mg tablet taken daily from Days 1 to 77. Part B: AZD9291 80mg tablet taken daily for 12 months.

Procedure/Surgery: Pharmacokinetic sampling - rifampicin
Blood sampling to measure rifampicin levels

Procedure/Surgery: Pharmacokinetic sampling - AZ5140 and AZ7550
Blood samples to measure levels of AZ5140 and AZ7550

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: 04 December 2014; Last Subject Last Visit Part A: 09 July 2015 and Part B: 29 June 2016. Study performed at 18 sites across Asia, North America and Western Europe. Part A assessed effect of multiple doses of rifampicin on PK of AZD9291; Part B allowed subjects further access to AZD9291 and provided additional safety data.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
51 patients were enrolled (signed informed consent). Patients were assigned to treatment if they met all the inclusion and none of the exclusion criteria. 10 subjects were enrolled but failed inclusion/exclusion criteria and so were not eligible to be assigned treatment. The remaining 41 patients started Period 1 and received treatment.

Reporting Groups

	Description
AZD9291 and Rifampicin (Part A); AZD9291 alone (Part B)	In Part A of the study, sequential treatments of AZD9291 alone, followed by AZD9291 + rifampicin, followed by AZD9291 alone. Each patient received 80 mg oral doses of AZD9291 tablets once daily for 77 days (Days 1 to 77) and additionally received 600 mg oral doses of rifampicin once daily on Days 29 to 49. In Part B of the study, each patient received 80 mg oral AZD9291 tablet formulation once daily, for the duration of their participation.

Description

AZD9291 and Rifampicin (Part A); AZD9291 alone (Part B)

In Part A of the study, sequential treatments of AZD9291 alone, followed by AZD9291 + rifampicin, followed by AZD9291 alone. Each patient received 80 mg oral doses of AZD9291 tablets once daily for 77 days (Days 1 to 77) and additionally received 600 mg oral doses of rifampicin once daily on Days 29 to 49.
In Part B of the study, each patient received 80 mg oral AZD9291 tablet formulation once daily, for the duration of their participation.

Participant Flow for 4 periods

Period 1: Part A: Day 1-28 (AZD9291 alone)

	AZD9291 and Rifampicin (Part A); AZD9291 alone (Part B)
STARTED	41
COMPLETED	41
NOT COMPLETED	0

Period 2: Part A: Day 29-49 (AZD9291+rifampicin)

	AZD9291 and Rifampicin (Part A); AZD9291 alone (Part B)
STARTED	41
COMPLETED	37
NOT COMPLETED	4
Adverse Event	2
Condition under investigation worsened	2

Period 3: Part A: Day 50-77 (AZD9291 alone)

	AZD9291 and Rifampicin (Part A); AZD9291 alone (Part B)
STARTED	37
COMPLETED	32
NOT COMPLETED	5
Condition under investigation worsened	5

Period 4: Part B: Day 78 to end Part B (AZD9291)

	AZD9291 and Rifampicin (Part A); AZD9291 alone (Part B)
STARTED	34^[1]
COMPLETED	19
NOT COMPLETED	15
Adverse Event	2
Withdrawal by Subject	2
Newly discovered brain metastases	1
Death	1
Condition under investigation worsened	9

[1]	32 completed Part A + 2 entered Part B without completing Part A (both due to AE) =34 started Part B

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 (n = 41) were included in the baseline analysis.

Reporting Groups

	Description
AZD9291 and Rifampicin (Part A); AZD9291 alone (Part B)	In Part A of the study, sequential treatments of AZD9291 alone, followed by AZD9291 + rifampicin, followed by AZD9291 alone. Each patient received 80 mg oral doses of AZD9291 tablets once daily for 77 days (Days 1 to 77) and additionally received 600 mg oral doses of rifampicin once daily on Days 29 to 49. In Part B of the study, each patient received 80 mg oral AZD9291 tablet formulation once daily, for the duration of their participation.

Description

AZD9291 and Rifampicin (Part A); AZD9291 alone (Part B)

In Part A of the study, sequential treatments of AZD9291 alone, followed by AZD9291 + rifampicin, followed by AZD9291 alone. Each patient received 80 mg oral doses of AZD9291 tablets once daily for 77 days (Days 1 to 77) and additionally received 600 mg oral doses of rifampicin once daily on Days 29 to 49. In Part B of the study, each patient received 80 mg oral AZD9291 tablet formulation once daily, for the duration of their participation.

Baseline Measures

	AZD9291 and Rifampicin (Part A); AZD9291 alone (Part B)
Number of Participants [units: Participants]	41
Age Continuous [units: years] Mean ± Standard Deviation	62.5 ± 11.74
Sex: Female, Male [units: ]
Female	32
Male	9
Race (NIH/OMB) [units: ]
American Indian or Alaska Native	0
Asian	15
Native Hawaiian or Other Pacific Islander	0
Black or African American	2
White	24
More than one race	0
Unknown or Not Reported	0

Outcome Measures

1. Primary Outcome Measure: Assessment of maximum plasma concentration for AZD9291 after dosing alone and in combination with rifampicin (Css,max) [ Time Frame: Samples collected on Day 28 following AZD9291 alone and Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A. ]

Measure Type	Primary
Measure Name	Assessment of maximum plasma concentration for AZD9291 after dosing alone and in combination with rifampicin (Css,max)
Measure Description	Rate and extent of absorption of AZD9291 by assessment of maximum plasma concentration at steady state (Css,max). AZD9291 doses were first without, then with rifampicin (Periods 1 and 2, respectively).
Time Frame	Samples collected on Day 28 following AZD9291 alone and Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A.
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 without any important deviations or events that would exclude the patient.

Reporting Groups

	Description
AZD9291 Alone (Period 1)	AZD9291 80 mg once daily on Days 1 to 28 (Part A). AZD9291 was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 28.
AZD9291 + Rifampicin (Period 2)	Concomitant treatment with AZD9291 80 mg once daily and rifampicin 600 mg once daily on Days 29 to 49 (Part A). All treatments (AZD9291 and rifampicin) were administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 49.

Measured Values

	AZD9291 Alone (Period 1)	AZD9291 + Rifampicin (Period 2)
Number of Participants Analyzed [units:participants]	38	32
Assessment of maximum plasma concentration for AZD9291 after dosing alone and in combination with rifampicin (Css,max) [units: nanomolar (nM)] Geometric Mean (Geometric Coefficient of Variation)	577.4 (44.7%)	147.5 (48.2%)

Statistical Analysis 1 for Assessment of maximum plasma concentration for AZD9291 after dosing alone and in combination with rifampicin (Css,max)

Groups^[1]	All groups
Other^[5]	27.16
90% Confidence Interval	( 24.36 to 30.29 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Natural log-transformed Css,max values were compared between periods using a mixed effects analysis of variance (ANOVA) with period as fixed effect and patient as random effect. It was assumed the within-patient coefficient of variation for AZD9291 in both area under the plasma concentration-time curve during the dosing interval (AUCtau) and Cmax was 34%. A 33% decrease in exposure for AZD9291 when given with rifampicin was also assumed.
[5]	Other relevant estimation information:
	AZD9291+rifampicin / AZD9291 alone (Period 2 versus Period 1).

2. Primary Outcome Measure: Assessment of area under the plasma concentration-time curve during the dosing interval for AZD9291 after dosing alone and in combination with rifampicin (AUCtau) [ Time Frame: Samples collected on Day 28 following AZD9291 alone and Day 49 following AZD9291 and rifampicin at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A. ]

Measure Type	Primary
Measure Name	Assessment of area under the plasma concentration-time curve during the dosing interval for AZD9291 after dosing alone and in combination with rifampicin (AUCtau)
Measure Description	Rate and extent of absorption of AZD9291 by assessment of AUCtau. AZD9291 doses were first without, then with rifampicin (Periods 1 and 2, respectively).
Time Frame	Samples collected on Day 28 following AZD9291 alone and Day 49 following AZD9291 and rifampicin at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A.
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 without any important deviations or events that would exclude the patient.

Reporting Groups

	Description
AZD9291 Alone (Period 1)	AZD9291 80 mg once daily on Days 1 to 28 (Part A). AZD9291 was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 28.
AZD9291 + Rifampicin (Period 2)	Concomitant treatment with AZD9291 80 mg once daily and rifampicin 600 mg once daily on Days 29 to 49 (Part A). All treatments (AZD9291 and rifampicin) were administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 49.

Measured Values

	AZD9291 Alone (Period 1)	AZD9291 + Rifampicin (Period 2)
Number of Participants Analyzed [units:participants]	38	32
Assessment of area under the plasma concentration-time curve during the dosing interval for AZD9291 after dosing alone and in combination with rifampicin (AUCtau) [units: nM * hour (nM*h)] Geometric Mean (Geometric Coefficient of Variation)	10870 (44.3%)	2192 (43.8%)

Statistical Analysis 1 for Assessment of area under the plasma concentration-time curve during the dosing interval for AZD9291 after dosing alone and in combination with rifampicin (AUCtau)

Groups^[1]	All groups
Other^[5]	21.55
90% Confidence Interval	( 19.50 to 23.83 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Natural log-transformed AUCtau values were compared between periods using a mixed effects ANOVA with period as fixed effect and patient as random effect. It was assumed the within-patient coefficient of variation for AZD9291 in both AUCtau and Cmax was 34%. A 33% decrease in exposure for AZD9291 when given with rifampicin was also assumed.
[5]	Other relevant estimation information:
	AZD9291+rifampicin / AZD9291 alone (Period 2 versus Period 1).

3. Secondary Outcome Measure: Assessment of Css,max for AZD9291 before and after rifampicin [ Time Frame: Samples collected on Day 28 and 77 following AZD9291 alone at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A. ]

Measure Type	Secondary
Measure Name	Assessment of Css,max for AZD9291 before and after rifampicin
Measure Description	Rate and extent of absorption of AZD9291 by assessment of Css,max. AZD9291 alone before rifampicin (Period 1) and AZD9291 alone after rifampicin (Period 3).
Time Frame	Samples collected on Day 28 and 77 following AZD9291 alone at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A.
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 without any important deviations or events that would exclude the patient.

Reporting Groups

	Description
AZD9291 Alone (Period 1)	AZD9291 80 mg once daily on Days 1 to 28 (Part A). AZD9291 was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 28.
AZD9291 Alone (Period 3)	AZD9291 80 mg once daily on Days 50 to 77 (Part A). AZD9291 was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 77.

Measured Values

	AZD9291 Alone (Period 1)	AZD9291 Alone (Period 3)
Number of Participants Analyzed [units:participants]	38	28
Assessment of Css,max for AZD9291 before and after rifampicin [units: nM] Geometric Mean (Geometric Coefficient of Variation)	577.4 (44.7%)	531.4 (37.9%)

Statistical Analysis 1 for Assessment of Css,max for AZD9291 before and after rifampicin

Groups^[1]	All groups
Other^[5]	95.53
90% Confidence Interval	( 85.27 to 107.03 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Natural log-transformed Css,max values were compared between periods using a mixed effects ANOVA with period as a fixed effect and patient as a random effect.
[5]	Other relevant estimation information:
	AZD9291 alone / AZD9291 alone (Period 3 versus Period 1). No pre-specified margins for equivalence test for AZD9291 alone in separate periods, but analysed for consistency with AZD9291+rifampicin / AZD9291 alone analysis (primary outcome measure).

4. Secondary Outcome Measure: Assessment of Css,max for AZ5104 (metabolite) [ Time Frame: Samples collected on Day 28 and 77 (following AZD9291 alone) and Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A. ]

Measure Type	Secondary
Measure Name	Assessment of Css,max for AZ5104 (metabolite)
Measure Description	Rate and extent of absorption of AZ5104 (metabolite) by assessment of Css,max. AZD9291 dosing alone and in combination with rifampicin (all periods).
Time Frame	Samples collected on Day 28 and 77 (following AZD9291 alone) and Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A.
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 without any important deviations or events that would exclude the patient.

Reporting Groups

	Description
AZD9291 Alone (Period 1)	AZD9291 80 mg once daily on Days 1 to 28 (Part A). AZD9291 was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 28.
AZD9291 + Rifampicin (Period 2)	Concomitant treatment with AZD9291 80 mg once daily and rifampicin 600 mg once daily on Days 29 to 49 (Part A). All treatments (AZD9291 and rifampicin) were administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 49.
AZD9291 Alone (Period 3)	AZD9291 80 mg once daily on Days 50 to 77 (Part A). AZD9291 was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 77.

Measured Values

	AZD9291 Alone (Period 1)	AZD9291 + Rifampicin (Period 2)	AZD9291 Alone (Period 3)
Number of Participants Analyzed [units:participants]	38	32	28
Assessment of Css,max for AZ5104 (metabolite) [units: nM] Geometric Mean (Geometric Coefficient of Variation)	60.40 (57.2%)	12.28 (52.6%)	50.73 (49.8%)

Statistical Analysis 1 for Assessment of Css,max for AZ5104 (metabolite)

Groups^[1]	AZD9291 Alone (Period 1), AZD9291 + Rifampicin (Period 2)
Other^[5]	21.72
90% Confidence Interval	( 19.08 to 24.72 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	For AZ5104 (metabolite), natural log-transformed Css,max values were compared between periods using a mixed effects ANOVA with period as a fixed effect and patient as a random effect.
[5]	Other relevant estimation information:
	AZD9291+rifampicin / AZD9291 alone (Period 2 versus Period 1). No pre-specified margins for equivalence test for metabolites, but analysed for consistency with AZD9291 analysis.

Statistical Analysis 2 for Assessment of Css,max for AZ5104 (metabolite)

Groups^[1]	AZD9291 Alone (Period 1), AZD9291 Alone (Period 3)
Other^[5]	88.31
90% Confidence Interval	( 77.17 to 101.07 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	For AZ5104 (metabolite), natural log-transformed Css,max values were compared between periods using a mixed effects ANOVA with period as a fixed effect and patient as a random effect.
[5]	Other relevant estimation information:
	AZD9291 alone / AZD9291 alone (Period 3 versus Period 1). No pre-specified margins for equivalence test for metabolites, but analysed for consistency with AZD9291 analysis.

5. Secondary Outcome Measure: Assessment of Css,max for AZ7550 (metabolite) [ Time Frame: Samples collected on Day 28 and 77 (following AZD9291 alone) and Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A. ]

Measure Type	Secondary
Measure Name	Assessment of Css,max for AZ7550 (metabolite)
Measure Description	Rate and extent of absorption of AZ7550 (metabolite) by assessment of Css,max. AZD9291 dosing alone and in combination with rifampicin (all periods).
Time Frame	Samples collected on Day 28 and 77 (following AZD9291 alone) and Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A.
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 without any important deviations or events that would exclude the patient.

Reporting Groups

	Description
AZD9291 Alone (Period 1)	AZD9291 80 mg once daily on Days 1 to 28 (Part A). AZD9291 was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 28.
AZD9291 + Rifampicin (Period 2)	Concomitant treatment with AZD9291 80 mg once daily and rifampicin 600 mg once daily on Days 29 to 49 (Part A). All treatments (AZD9291 and rifampicin) were administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 49.
AZD9291 Alone (Period 3)	AZD9291 80 mg once daily on Days 50 to 77 (Part A). AZD9291 was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 77.

Measured Values

	AZD9291 Alone (Period 1)	AZD9291 + Rifampicin (Period 2)	AZD9291 Alone (Period 3)
Number of Participants Analyzed [units:participants]	38	32	28
Assessment of Css,max for AZ7550 (metabolite) [units: nM] Geometric Mean (Geometric Coefficient of Variation)	53.54 (43.7%)	73.14 (25.0%)	53.24 (34.4%)

Statistical Analysis 1 for Assessment of Css,max for AZ7550 (metabolite)

Groups^[1]	AZD9291 Alone (Period 1), AZD9291 + Rifampicin (Period 2)
Other^[5]	139.32
90% Confidence Interval	( 127.74 to 151.96 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	For AZ7550 (metabolite), natural log-transformed Css,max values were compared between periods using a mixed effects ANOVA with period as a fixed effect and patient as a random effect.
[5]	Other relevant estimation information:
	AZD9291+rifampicin / AZD9291 alone (Period 2 versus Period 1). No pre-specified margins for equivalence test for metabolites, but analysed for consistency with AZD9291 analysis.

Statistical Analysis 2 for Assessment of Css,max for AZ7550 (metabolite)

Groups^[1]	AZD9291 Alone (Period 1), AZD9291 Alone (Period 3)
Other^[5]	100.75
90% Confidence Interval	( 92.04 to 110.29 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	For AZ7550 (metabolite), natural log-transformed Css,max values were compared between periods using a mixed effects ANOVA with period as a fixed effect and patient as a random effect.
[5]	Other relevant estimation information:
	AZD9291 alone / AZD9291 alone (Period 3 versus Period 1). No pre-specified margins for equivalence test for metabolites, but analysed for consistency with AZD9291 analysis.

6. Secondary Outcome Measure: Assessment of Css,max for rifampicin [ Time Frame: Samples collected on Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A. ]

Measure Type	Secondary
Measure Name	Assessment of Css,max for rifampicin
Measure Description	Rate and extent of absorption of rifampicin by assessment of Css,max. AZD9291 dosing in combination with rifampicin (Period 2).
Time Frame	Samples collected on Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A.
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 without any important deviations or events that would exclude the patient.

Reporting Groups

	Description
AZD9291 + Rifampicin (Period 2)	Concomitant treatment with AZD9291 80 mg once daily and rifampicin 600 mg once daily on Days 29 to 49 (Part A). All treatments (AZD9291 and rifampicin) were administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 49.

Measured Values

	AZD9291 + Rifampicin (Period 2)
Number of Participants Analyzed [units:participants]	32
Assessment of Css,max for rifampicin [units: nanogram per millilitre (ng/mL)] Geometric Mean (Geometric Coefficient of Variation)	13810 (40.6%)

No statistical analysis provided for Assessment of Css,max for rifampicin

7. Secondary Outcome Measure: Assessment of AUCtau for AZD9291 before and after rifampicin [ Time Frame: Samples collected on Day 28 and 77 following AZD9291 alone at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A. ]

Measure Type	Secondary
Measure Name	Assessment of AUCtau for AZD9291 before and after rifampicin
Measure Description	Rate and extent of absorption of AZD9291 by assessment of AUCtau. AZD9291 alone before rifampicin (Period 1) and AZD9291 alone after rifampicin (Period 3).
Time Frame	Samples collected on Day 28 and 77 following AZD9291 alone at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A.
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 without any important deviations or events that would exclude the patient.

Reporting Groups

	Description
AZD9291 Alone (Period 1)	AZD9291 80 mg once daily on Days 1 to 28 (Part A). AZD9291 was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 28.
AZD9291 Alone (Period 3)	AZD9291 80 mg once daily on Days 50 to 77 (Part A). AZD9291 was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 77.

Measured Values

	AZD9291 Alone (Period 1)	AZD9291 Alone (Period 3)
Number of Participants Analyzed [units:participants]	38	28
Assessment of AUCtau for AZD9291 before and after rifampicin [units: nM*h] Geometric Mean (Geometric Coefficient of Variation)	10870 (44.3%)	10060 (36.8%)

Statistical Analysis 1 for Assessment of AUCtau for AZD9291 before and after rifampicin

Groups^[1]	All groups
Other^[5]	95.89
90% Confidence Interval	( 86.37 to 106.45 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Natural log-transformed AUCtau values were compared between periods using a mixed effects ANOVA with period as a fixed effect and patient as a random effect.
[5]	Other relevant estimation information:
	AZD9291 alone / AZD9291 alone (Period 3 versus Period 1). No pre-specified margins for equivalence test for AZD9291 alone in separate periods, but analysed for consistency with AZD9291+rifampicin / AZD9291 alone analysis (primary outcome measure).

8. Secondary Outcome Measure: Assessment of AUCtau for AZ5104 (metabolite) [ Time Frame: Samples collected on Day 28 and 77 (following AZD9291 alone) and Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A. ]

Measure Type	Secondary
Measure Name	Assessment of AUCtau for AZ5104 (metabolite)
Measure Description	Rate and extent of absorption of AZ5104 (metabolite) by assessment of AUCtau. AZD9291 dosing alone and in combination with rifampicin (all periods).
Time Frame	Samples collected on Day 28 and 77 (following AZD9291 alone) and Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A.
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 without any important deviations or events that would exclude the patient.

Reporting Groups

	Description
AZD9291 Alone (Period 1)	AZD9291 80 mg once daily on Days 1 to 28 (Part A). AZD9291 was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 28.
AZD9291 + Rifampicin (Period 2)	Concomitant treatment with AZD9291 80 mg once daily and rifampicin 600 mg once daily on Days 29 to 49 (Part A). All treatments (AZD9291 and rifampicin) were administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 49.
AZD9291 Alone (Period 3)	AZD9291 80 mg once daily on Days 50 to 77 (Part A). AZD9291 was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 77.

Measured Values

	AZD9291 Alone (Period 1)	AZD9291 + Rifampicin (Period 2)	AZD9291 Alone (Period 3)
Number of Participants Analyzed [units:participants]	38	32	28
Assessment of AUCtau for AZ5104 (metabolite) [units: nM*h] Geometric Mean (Geometric Coefficient of Variation)	1206 (55.8%)	210.3 (48.0%)	1029 (49.7%)

Statistical Analysis 1 for Assessment of AUCtau for AZ5104 (metabolite)

Groups^[1]	AZD9291 Alone (Period 1), AZD9291 + Rifampicin (Period 2)
Other^[5]	18.76
90% Confidence Interval	( 16.61 to 21.19 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	For AZ5104 (metabolite), natural log-transformed AUCtau values were compared between periods using a mixed effects ANOVA with period as a fixed effect and patient as a random effect.
[5]	Other relevant estimation information:
	AZD9291+rifampicin / AZD9291 alone (Period 2 versus Period 1). No pre-specified margins for equivalence test for metabolites, but analysed for consistency with AZD9291 analysis.

Statistical Analysis 2 for Assessment of AUCtau for AZ5104 (metabolite)

Groups^[1]	AZD9291 Alone (Period 1), AZD9291 Alone (Period 3)
Other^[5]	90.08
90% Confidence Interval	( 79.34 to 102.27 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	For AZ5104 (metabolite), natural log-transformed AUCtau values were compared between periods using a mixed effects ANOVA with period as a fixed effect and patient as a random effect.
[5]	Other relevant estimation information:
	AZD9291 alone / AZD9291 alone (Period 3 versus Period 1). No pre-specified margins for equivalence test for metabolites, but analysed for consistency with AZD9291 analysis.

9. Secondary Outcome Measure: Assessment of AUCtau for AZ7550 (metabolite) [ Time Frame: Samples collected on Day 28 and 77 (following AZD9291 alone) and Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A. ]

Measure Type	Secondary
Measure Name	Assessment of AUCtau for AZ7550 (metabolite)
Measure Description	Rate and extent of absorption of AZ7550 (metabolite) by assessment of AUCtau. AZD9291 dosing alone and in combination with rifampicin (all periods).
Time Frame	Samples collected on Day 28 and 77 (following AZD9291 alone) and Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A.
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 without any important deviations or events that would exclude the patient.

Reporting Groups

	Description
AZD9291 Alone (Period 1)	AZD9291 80 mg once daily on Days 1 to 28 (Part A). AZD9291 was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 28.
AZD9291 + Rifampicin (Period 2)	Concomitant treatment with AZD9291 80 mg once daily and rifampicin 600 mg once daily on Days 29 to 49 (Part A). All treatments (AZD9291 and rifampicin) were administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 49.
AZD9291 Alone (Period 3)	AZD9291 80 mg once daily on Days 50 to 77 (Part A). AZD9291 was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 77.

Measured Values

	AZD9291 Alone (Period 1)	AZD9291 + Rifampicin (Period 2)	AZD9291 Alone (Period 3)
Number of Participants Analyzed [units:participants]	38	32	28
Assessment of AUCtau for AZ7550 (metabolite) [units: nM*h] Geometric Mean (Geometric Coefficient of Variation)	1107 (41.7%)	1416 (25.6%)	1111 (31.7%)

Statistical Analysis 1 for Assessment of AUCtau for AZ7550 (metabolite)

Groups^[1]	AZD9291 Alone (Period 1), AZD9291 + Rifampicin (Period 2)
Other^[5]	129.81
90% Confidence Interval	( 119.14 to 141.44 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	For AZ7550 (metabolite), natural log-transformed AUCtau values were compared between periods using a mixed effects ANOVA with period as a fixed effect and patient as a random effect.
[5]	Other relevant estimation information:
	AZD9291+rifampicin / AZD9291 alone (Period 2 versus Period 1). No pre-specified margins for equivalence test for metabolites, but analysed for consistency with AZD9291 analysis.

Statistical Analysis 2 for Assessment of AUCtau for AZ7550 (metabolite)

Groups^[1]	AZD9291 Alone (Period 1), AZD9291 Alone (Period 3)
Other^[5]	100.76
90% Confidence Interval	( 92.15 to 110.19 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	For AZ7550 (metabolite), natural log-transformed AUCtau values were compared between periods using a mixed effects ANOVA with period as a fixed effect and patient as a random effect.
[5]	Other relevant estimation information:
	AZD9291 alone / AZD9291 alone (Period 3 versus Period 1). No pre-specified margins for equivalence test for metabolites, but analysed for consistency with AZD9291 analysis.

10. Secondary Outcome Measure: Assessment of AUCtau for rifampicin [ Time Frame: Samples collected on Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A. ]

Measure Type	Secondary
Measure Name	Assessment of AUCtau for rifampicin
Measure Description	Rate and extent of absorption of rifampicin by assessment of AUCtau. AZD9291 dosing in combination with rifampicin (Period 2).
Time Frame	Samples collected on Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A.
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 without any important deviations or events that would exclude the patient.

Reporting Groups

	Description
AZD9291 + Rifampicin (Period 2)	Concomitant treatment with AZD9291 80 mg once daily and rifampicin 600 mg once daily on Days 29 to 49 (Part A). All treatments (AZD9291 and rifampicin) were administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 49.

Measured Values

	AZD9291 + Rifampicin (Period 2)
Number of Participants Analyzed [units:participants]	32
Assessment of AUCtau for rifampicin [units: ng*h/mL] Geometric Mean (Geometric Coefficient of Variation)	58610 (36.8%)

No statistical analysis provided for Assessment of AUCtau for rifampicin

11. Secondary Outcome Measure: Assessment of tss,max for AZD9291, and AZ5104 and AZ7550 (metabolites) [ Time Frame: Samples collected on Day 28 and 77 (following AZD9291 alone) and Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A. ]

Measure Type	Secondary
Measure Name	Assessment of tss,max for AZD9291, and AZ5104 and AZ7550 (metabolites)
Measure Description	Rate and extent of absorption of AZD9291, and AZ5104 and AZ7550 (metabolites) by assessment of time to reach maximum plasma concentration at steady state (tss,max). AZD9291 dosing alone and in combination with rifampicin (all periods).
Time Frame	Samples collected on Day 28 and 77 (following AZD9291 alone) and Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A.
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 without any important deviations or events that would exclude the patient.

Reporting Groups

	Description
AZD9291 Alone (Period 1)	AZD9291 80 mg once daily on Days 1 to 28 (Part A). AZD9291 was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 28.
AZD9291 + Rifampicin (Period 2)	Concomitant treatment with AZD9291 80 mg once daily and rifampicin 600 mg once daily on Days 29 to 49 (Part A). All treatments (AZD9291 and rifampicin) were administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 49.
AZD9291 Alone (Period 3)	AZD9291 80 mg once daily on Days 50 to 77 (Part A). AZD9291 was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 77.

Measured Values

	AZD9291 Alone (Period 1)	AZD9291 + Rifampicin (Period 2)	AZD9291 Alone (Period 3)
Number of Participants Analyzed [units:participants]	38	32	28
Assessment of tss,max for AZD9291, and AZ5104 and AZ7550 (metabolites) [units: h] Median (Full Range)
AZD9291 tss,max	4.97 (2.88 to 9.88)	5.88 (3.00 to 10.00)	6.00 (3.17 to 23.92)
AZ5104 tss,max	6.00 (0.00 to 24.00)	6.03 (3.00 to 11.43)	6.00 (0.00 to 24.00)
AZ7550 tss,max	6.14 (2.88 to 24.92)	7.95 (4.00 to 12.00)	7.03 (1.10 to 24.00)

No statistical analysis provided for Assessment of tss,max for AZD9291, and AZ5104 and AZ7550 (metabolites)

12. Secondary Outcome Measure: Assessment of tss,max for rifampicin [ Time Frame: Samples collected on Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A. ]

Measure Type	Secondary
Measure Name	Assessment of tss,max for rifampicin
Measure Description	Rate and extent of absorption of rifampicin by assessment of tss,max. AZD9291 dosing in combination with rifampicin (Period 2).
Time Frame	Samples collected on Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A.
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 without any important deviations or events that would exclude the patient.

Reporting Groups

	Description
AZD9291 + Rifampicin (Period 2)	Concomitant treatment with AZD9291 80 mg once daily and rifampicin 600 mg once daily on Days 29 to 49 (Part A). All treatments (AZD9291 and rifampicin) were administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 49.

Measured Values

	AZD9291 + Rifampicin (Period 2)
Number of Participants Analyzed [units:participants]	32
Assessment of tss,max for rifampicin [units: h] Median (Full Range)	2.00 (0.83 to 6.07)

No statistical analysis provided for Assessment of tss,max for rifampicin

13. Secondary Outcome Measure: Assessment of Css,min for AZD9291, and AZ5104 and AZ7550 (metabolites) [ Time Frame: Samples collected on Day 28 and 77 (following AZD9291 alone) and Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A. ]

Measure Type	Secondary
Measure Name	Assessment of Css,min for AZD9291, and AZ5104 and AZ7550 (metabolites)
Measure Description	Rate and extent of absorption of AZD9291, and AZ5104 and AZ7550 (metabolites) by assessment of minimum plasma concentration at steady state (Css,min). AZD9291 dosing alone and in combination with rifampicin (all periods).
Time Frame	Samples collected on Day 28 and 77 (following AZD9291 alone) and Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A.
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 without any important deviations or events that would exclude the patient.

Reporting Groups

	Description
AZD9291 Alone (Period 1)	AZD9291 80 mg once daily on Days 1 to 28 (Part A). AZD9291 was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 28.
AZD9291 + Rifampicin (Period 2)	Concomitant treatment with AZD9291 80 mg once daily and rifampicin 600 mg once daily on Days 29 to 49 (Part A). All treatments (AZD9291 and rifampicin) were administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 49.
AZD9291 Alone (Period 3)	AZD9291 80 mg once daily on Days 50 to 77 (Part A). AZD9291 was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 77.

Measured Values

	AZD9291 Alone (Period 1)	AZD9291 + Rifampicin (Period 2)	AZD9291 Alone (Period 3)
Number of Participants Analyzed [units:participants]	38	31	28
Assessment of Css,min for AZD9291, and AZ5104 and AZ7550 (metabolites) [units: nM] Geometric Mean (Geometric Coefficient of Variation)
AZD9291 Css,min	354.7 (52.4%)	50.56 (47.9%)	326.9 (41.1%)
AZ5104 Css,min	41.80 (62.1%)	5.816 (51.6%)	35.37 (51.4%)
AZ7550 Css,min	37.99 (44.0%)	44.89 (26.9%)	37.68 (35.4%)

No statistical analysis provided for Assessment of Css,min for AZD9291, and AZ5104 and AZ7550 (metabolites)

14. Secondary Outcome Measure: Assessment of Css,min for rifampicin [ Time Frame: Samples collected on Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A. ]

Measure Type	Secondary
Measure Name	Assessment of Css,min for rifampicin
Measure Description	Rate and extent of absorption of rifampicin by assessment of minimum plasma concentration at steady state (Css,min). AZD9291 dosing in combination with rifampicin (Period 2).
Time Frame	Samples collected on Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A.
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 without any important deviations or events that would exclude the patient.

Reporting Groups

	Description
AZD9291 + Rifampicin (Period 2)	Concomitant treatment with AZD9291 80 mg once daily and rifampicin 600 mg once daily on Days 29 to 49 (Part A). All treatments (AZD9291 and rifampicin) were administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 49.

Measured Values

	AZD9291 + Rifampicin (Period 2)
Number of Participants Analyzed [units:participants]	32
Assessment of Css,min for rifampicin [units: ng/mL] Geometric Mean (Geometric Coefficient of Variation)	NA (NA%)^[1]

No statistical analysis provided for Assessment of Css,min for rifampicin

15. Secondary Outcome Measure: Assessment of CLss/F for AZD9291 [ Time Frame: Samples collected on Day 28 and 77 (following AZD9291 alone) and Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A. ]

Measure Type	Secondary
Measure Name	Assessment of CLss/F for AZD9291
Measure Description	Rate and extent of absorption of AZD9291 by assessment of the apparent plasma clearance following oral administration and multiple dosing (CLss/F). AZD9291 dosing alone and in combination with rifampicin (all periods).
Time Frame	Samples collected on Day 28 and 77 (following AZD9291 alone) and Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A.
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.

Reporting Groups

	Description
AZD9291 Alone (Period 1)	AZD9291 80 mg once daily on Days 1 to 28 (Part A). AZD9291 was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 28.
AZD9291 + Rifampicin (Period 2)	Concomitant treatment with AZD9291 80 mg once daily and rifampicin 600 mg once daily on Days 29 to 49 (Part A). All treatments (AZD9291 and rifampicin) were administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 49.
AZD9291 Alone (Period 3)	AZD9291 80 mg once daily on Days 50 to 77 (Part A). AZD9291 was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 77.

Measured Values

	AZD9291 Alone (Period 1)	AZD9291 + Rifampicin (Period 2)	AZD9291 Alone (Period 3)
Number of Participants Analyzed [units:participants]	38	32	28
Assessment of CLss/F for AZD9291 [units: Litre per hour (L/h)] Geometric Mean (Geometric Coefficient of Variation)	14.74 (44.2%)	73.07 (43.8%)	15.92 (36.7%)

No statistical analysis provided for Assessment of CLss/F for AZD9291

16. Secondary Outcome Measure: Assessment of CLss/F for rifampicin [ Time Frame: Samples collected on Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A. ]

Measure Type	Secondary
Measure Name	Assessment of CLss/F for rifampicin
Measure Description	Rate and extent of absorption of rifampicin by assessment of CLss/F. AZD9291 dosing in combination with rifampicin (Period 2).
Time Frame	Samples collected on Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A.
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.

Reporting Groups

	Description
AZD9291 + Rifampicin (Period 2)	Concomitant treatment with AZD9291 80 mg once daily and rifampicin 600 mg once daily on Days 29 to 49 (Part A). All treatments (AZD9291 and rifampicin) were administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 49.

Measured Values

	AZD9291 + Rifampicin (Period 2)
Number of Participants Analyzed [units:participants]	32
Assessment of CLss/F for rifampicin [units: L/h] Geometric Mean (Geometric Coefficient of Variation)	10.23 (36.7%)

No statistical analysis provided for Assessment of CLss/F for rifampicin

17. Secondary Outcome Measure: Assessment of the metabolic ratios of Css,max for AZ5104 and AZ7550 (MRCss,max) [ Time Frame: Samples collected on Day 28 and 77 (following AZD9291 alone) and Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A. ]

Measure Type	Secondary
Measure Name	Assessment of the metabolic ratios of Css,max for AZ5104 and AZ7550 (MRCss,max)
Measure Description	Assessment of the metabolite to parent ratio (calculated as AZ5104 to AZD9291 and AZ7550 to AZD9291) for Css,max (MRCss,max). AZD9291 dosing alone and in combination with rifampicin (all periods).
Time Frame	Samples collected on Day 28 and 77 (following AZD9291 alone) and Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A.
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 without any important deviations or events that would exclude the patient.

Reporting Groups

	Description
AZD9291 Alone (Period 1)	AZD9291 80 mg once daily on Days 1 to 28 (Part A). AZD9291 was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 28.
AZD9291 + Rifampicin (Period 2)	Concomitant treatment with AZD9291 80 mg once daily and rifampicin 600 mg once daily on Days 29 to 49 (Part A). All treatments (AZD9291 and rifampicin) were administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 49.
AZD9291 Alone (Period 3)	AZD9291 80 mg once daily on Days 50 to 77 (Part A). AZD9291 was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 77.

Measured Values

	AZD9291 Alone (Period 1)	AZD9291 + Rifampicin (Period 2)	AZD9291 Alone (Period 3)
Number of Participants Analyzed [units:participants]	38	32	28
Assessment of the metabolic ratios of Css,max for AZ5104 and AZ7550 (MRCss,max) [units: Ratio] Geometric Mean (Geometric Coefficient of Variation)
AZ5104 Css,max / AZD9291 Css,max	0.1046 (31.0%)	0.08327 (27.4%)	0.09544 (27.4%)
AZ7550 Css,max / AZD9291 Css,max	0.09276 (49.3%)	0.4960 (33.1%)	0.1002 (38.1%)

No statistical analysis provided for Assessment of the metabolic ratios of Css,max for AZ5104 and AZ7550 (MRCss,max)

18. Secondary Outcome Measure: Assessment of the metabolic ratios of AUCtau for AZ5104 and AZ7550 (MRAUCtau) [ Time Frame: Samples collected on Day 28 and 77 (following AZD9291 alone) and Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A. ]

Measure Type	Secondary
Measure Name	Assessment of the metabolic ratios of AUCtau for AZ5104 and AZ7550 (MRAUCtau)
Measure Description	Assessment of the metabolite to parent ratio (calculated as AZ5104 to AZD9291 and AZ7550 to AZD9291) for AUCtau (MRAUCtau). AZD9291 dosing alone and in combination with rifampicin (all periods).
Time Frame	Samples collected on Day 28 and 77 (following AZD9291 alone) and Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A.
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 without any important deviations or events that would exclude the patient.

Reporting Groups

	Description
AZD9291 Alone (Period 1)	AZD9291 80 mg once daily on Days 1 to 28 (Part A). AZD9291 was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 28.
AZD9291 + Rifampicin (Period 2)	Concomitant treatment with AZD9291 80 mg once daily and rifampicin 600 mg once daily on Days 29 to 49 (Part A). All treatments (AZD9291 and rifampicin) were administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 49.
AZD9291 Alone (Period 3)	AZD9291 80 mg once daily on Days 50 to 77 (Part A). AZD9291 was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after AZD9291 administration on Day 77.

Measured Values

	AZD9291 Alone (Period 1)	AZD9291 + Rifampicin (Period 2)	AZD9291 Alone (Period 3)
Number of Participants Analyzed [units:participants]	38	32	28
Assessment of the metabolic ratios of AUCtau for AZ5104 and AZ7550 (MRAUCtau) [units: Ratio] Geometric Mean (Geometric Coefficient of Variation)
AZ5104 AUCtau / AZD9291 AUCtau	0.1109 (29.0%)	0.09595 (23.6%)	0.1023 (28.5%)
AZ7550 AUCtau / AZD9291 AUCtau	0.1019 (52.3%)	0.6459 (28.2%)	0.1104 (38.8%)

No statistical analysis provided for Assessment of the metabolic ratios of AUCtau for AZ5104 and AZ7550 (MRAUCtau)

Serious Adverse Events

Time Frame	Approximately 3 months for Part A; up to approximately 14 months for Part B and approximately 17 months for Overall (Parts A and B combined).
Additional Description	Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 77), or until 30 days after last dose if discontinued in Part A. Part B: AEs collected from day of first dose in Part B until 30 days after last dose, or until last dose in Part B for those entering continued access phase (CAP).

Reporting Groups

	Description
Overall	Parts A and B of the study combined.
Part A	In Part A of the study, each patient received 80 mg oral doses of AZD9291 tablets once daily for 77 days (Days 1 to 77) and additionally received 600 mg oral doses of rifampicin once daily on Days 29 to 49.
Part B	In Part B of the study, each patient received 80 mg oral AZD9291 tablet formulation once daily, for the duration of their participation.

Serious Adverse Events

Overall

Part A

Part B

Total, serious adverse events

# participants affected / at risk

11/41 (26.83%)

7/41 (17.07%)

6/34 (17.65%)

Cardiac disorders

Atrial fibrillation¹,^†

# participants affected / at risk

1/41 (2.44%)

0/41 (0.00%)

1/34 (2.94%)

# events

Infections and infestations

Influenza¹,^†

# participants affected / at risk

2/41 (4.88%)

1/41 (2.44%)

1/34 (2.94%)

# events

Cardiac disorders

Cardiac failure congestive¹,^†

# participants affected / at risk

1/41 (2.44%)

0/34 (0.00%)

# events

Gastrointestinal disorders

Ileus¹,^†

# participants affected / at risk

1/41 (2.44%)

0/41 (0.00%)

1/34 (2.94%)

# events

General disorders and administration site conditions

Malaise¹,^†

# participants affected / at risk

1/41 (2.44%)

0/34 (0.00%)

# events

Infections and infestations

Hepatitis B¹,^†

# participants affected / at risk

1/41 (2.44%)

0/41 (0.00%)

1/34 (2.94%)

# events

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

1/41 (2.44%)

0/41 (0.00%)

1/34 (2.94%)

# events

Infections and infestations

Pulmonary sepsis¹,^†

# participants affected / at risk

1/41 (2.44%)

0/41 (0.00%)

1/34 (2.94%)

# events

Injury, poisoning and procedural complications

Femur fracture¹,^†

# participants affected / at risk

1/41 (2.44%)

0/34 (0.00%)

# events

Metabolism and nutrition disorders

Hyperkalaemia¹,^†

# participants affected / at risk

1/41 (2.44%)

0/34 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Muscular weakness¹,^†

# participants affected / at risk

1/41 (2.44%)

0/34 (0.00%)

# events

Nervous system disorders

Thrombotic stroke¹,^†

# participants affected / at risk

1/41 (2.44%)

0/41 (0.00%)

1/34 (2.94%)

# events

Vascular disorders

Thrombophlebitis¹,^†

# participants affected / at risk

1/41 (2.44%)

0/34 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 19.0

Other Adverse Events

Time Frame	Approximately 3 months for Part A; up to approximately 14 months for Part B and approximately 17 months for Overall (Parts A and B combined).
Additional Description	Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 77), or until 30 days after last dose if discontinued in Part A. Part B: AEs collected from day of first dose in Part B until 30 days after last dose, or until last dose in Part B for those entering continued access phase (CAP).

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Overall	Parts A and B of the study combined.
Part A	In Part A of the study, each patient received 80 mg oral doses of AZD9291 tablets once daily for 77 days (Days 1 to 77) and additionally received 600 mg oral doses of rifampicin once daily on Days 29 to 49.
Part B	In Part B of the study, each patient received 80 mg oral AZD9291 tablet formulation once daily, for the duration of their participation.

Other Adverse Events

Overall

Part A

Part B

Total, other (not including serious) adverse events

# participants affected / at risk

40/41 (97.56%)

39/41 (95.12%)

34/34 (100.00%)

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

6/41 (14.63%)

3/41 (7.32%)

3/34 (8.82%)

# events

Eye disorders

Eye pruritus¹,^†

# participants affected / at risk

2/41 (4.88%)

0/41 (0.00%)

2/34 (5.88%)

# events

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

7/41 (17.07%)

4/41 (9.76%)

5/34 (14.71%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

22/41 (53.66%)

14/41 (34.15%)

14/34 (41.18%)

# events

General disorders and administration site conditions

Oedema peripheral¹,^†

# participants affected / at risk

7/41 (17.07%)

4/41 (9.76%)

3/34 (8.82%)

# events

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

6/41 (14.63%)

4/41 (9.76%)

2/34 (5.88%)

# events

Investigations

Weight decreased¹,^†

# participants affected / at risk

7/41 (17.07%)

3/41 (7.32%)

4/34 (11.76%)

# events

Metabolism and nutrition disorders

Decreased appetite¹,^†

# participants affected / at risk

19/41 (46.34%)

6/41 (14.63%)

13/34 (38.24%)

# events

Metabolism and nutrition disorders

Iron deficiency¹,^†

# participants affected / at risk

2/41 (4.88%)

0/41 (0.00%)

2/34 (5.88%)

# events

Blood and lymphatic system disorders

Neutropenia¹,^†

# participants affected / at risk

3/41 (7.32%)

2/41 (4.88%)

2/34 (5.88%)

# events

Eye disorders

Dry eye¹,^†

# participants affected / at risk

4/41 (9.76%)

3/41 (7.32%)

2/34 (5.88%)

# events

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

5/41 (12.20%)

2/41 (4.88%)

3/34 (8.82%)

# events

Gastrointestinal disorders

Abdominal pain upper¹,^†

# participants affected / at risk

2/41 (4.88%)

0/41 (0.00%)

2/34 (5.88%)

# events

Gastrointestinal disorders

Dyspepsia¹,^†

# participants affected / at risk

3/41 (7.32%)

2/41 (4.88%)

1/34 (2.94%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

13/41 (31.71%)

8/41 (19.51%)

9/34 (26.47%)

# events

Gastrointestinal disorders

Stomatitis¹,^†

# participants affected / at risk

10/41 (24.39%)

6/41 (14.63%)

6/34 (17.65%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

11/41 (26.83%)

5/41 (12.20%)

7/34 (20.59%)

# events

General disorders and administration site conditions

Asthenia¹,^†

# participants affected / at risk

7/41 (17.07%)

4/41 (9.76%)

3/34 (8.82%)

# events

General disorders and administration site conditions

Face oedema¹,^†

# participants affected / at risk

3/41 (7.32%)

2/41 (4.88%)

1/34 (2.94%)

# events

General disorders and administration site conditions

Fatigue¹,^†

# participants affected / at risk

13/41 (31.71%)

8/41 (19.51%)

5/34 (14.71%)

# events

General disorders and administration site conditions

Non-cardiac chest pain¹,^†

# participants affected / at risk

3/41 (7.32%)

1/41 (2.44%)

2/34 (5.88%)

# events

General disorders and administration site conditions

Pyrexia¹,^†

# participants affected / at risk

5/41 (12.20%)

1/41 (2.44%)

4/34 (11.76%)

# events

Infections and infestations

Folliculitis¹,^†

# participants affected / at risk

2/41 (4.88%)

0/41 (0.00%)

2/34 (5.88%)

# events

Infections and infestations

Influenza¹,^†

# participants affected / at risk

2/41 (4.88%)

0/41 (0.00%)

2/34 (5.88%)

# events

Infections and infestations

Lower respiratory tract infection¹,^†

# participants affected / at risk

3/41 (7.32%)

2/41 (4.88%)

1/34 (2.94%)

# events

Infections and infestations

Paronychia¹,^†

# participants affected / at risk

8/41 (19.51%)

2/41 (4.88%)

6/34 (17.65%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

6/41 (14.63%)

2/34 (5.88%)

# events

Investigations

Alanine aminotransferase increased¹,^†

# participants affected / at risk

3/41 (7.32%)

1/41 (2.44%)

2/34 (5.88%)

# events

Investigations

Blood creatinine increased¹,^†

# participants affected / at risk

3/41 (7.32%)

1/41 (2.44%)

2/34 (5.88%)

# events

Investigations

Electrocardiogram QT prolonged¹,^†

# participants affected / at risk

3/41 (7.32%)

0/41 (0.00%)

3/34 (8.82%)

# events

Investigations

Neutrophil count decreased¹,^†

# participants affected / at risk

3/41 (7.32%)

2/41 (4.88%)

2/34 (5.88%)

# events

Investigations

Platelet count decreased¹,^†

# participants affected / at risk

5/41 (12.20%)

2/41 (4.88%)

4/34 (11.76%)

# events

Metabolism and nutrition disorders

Hyperkalaemia¹,^†

# participants affected / at risk

3/41 (7.32%)

2/41 (4.88%)

1/34 (2.94%)

# events

Metabolism and nutrition disorders

Hypokalaemia¹,^†

# participants affected / at risk

2/41 (4.88%)

0/41 (0.00%)

2/34 (5.88%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

5/41 (12.20%)

3/41 (7.32%)

3/34 (8.82%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

11/41 (26.83%)

6/41 (14.63%)

5/34 (14.71%)

# events

Musculoskeletal and connective tissue disorders

Muscle spasms¹,^†

# participants affected / at risk

2/41 (4.88%)

0/41 (0.00%)

2/34 (5.88%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal chest pain¹,^†

# participants affected / at risk

2/41 (4.88%)

0/41 (0.00%)

2/34 (5.88%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal pain¹,^†

# participants affected / at risk

9/41 (21.95%)

4/41 (9.76%)

5/34 (14.71%)

# events

Musculoskeletal and connective tissue disorders

Myalgia¹,^†

# participants affected / at risk

3/41 (7.32%)

1/41 (2.44%)

2/34 (5.88%)

# events

Musculoskeletal and connective tissue disorders

Pain in extremity¹,^†

# participants affected / at risk

4/41 (9.76%)

2/41 (4.88%)

2/34 (5.88%)

# events

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

3/41 (7.32%)

0/41 (0.00%)

3/34 (8.82%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

8/41 (19.51%)

7/41 (17.07%)

2/34 (5.88%)

# events

Psychiatric disorders

Insomnia¹,^†

# participants affected / at risk

3/41 (7.32%)

2/41 (4.88%)

1/34 (2.94%)

# events

Renal and urinary disorders

Haematuria¹,^†

# participants affected / at risk

3/41 (7.32%)

2/41 (4.88%)

1/34 (2.94%)

# events

Renal and urinary disorders

Pollakiuria¹,^†

# participants affected / at risk

3/41 (7.32%)

0/34 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

10/41 (24.39%)

7/41 (17.07%)

4/34 (11.76%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

5/41 (12.20%)

3/41 (7.32%)

2/34 (5.88%)

# events

Respiratory, thoracic and mediastinal disorders

Oropharyngeal pain¹,^†

# participants affected / at risk

4/41 (9.76%)

3/41 (7.32%)

1/34 (2.94%)

# events

Skin and subcutaneous tissue disorders

Alopecia¹,^†

# participants affected / at risk

2/41 (4.88%)

0/41 (0.00%)

2/34 (5.88%)

# events

Skin and subcutaneous tissue disorders

Dermatitis acneiform¹,^†

# participants affected / at risk

3/41 (7.32%)

2/41 (4.88%)

1/34 (2.94%)

# events

Skin and subcutaneous tissue disorders

Dry skin¹,^†

# participants affected / at risk

17/41 (41.46%)

10/41 (24.39%)

12/34 (35.29%)

# events

Skin and subcutaneous tissue disorders

Nail discolouration¹,^†

# participants affected / at risk

2/41 (4.88%)

0/41 (0.00%)

2/34 (5.88%)

# events

Skin and subcutaneous tissue disorders

Pruritus¹,^†

# participants affected / at risk

6/41 (14.63%)

4/41 (9.76%)

4/34 (11.76%)

# events

Skin and subcutaneous tissue disorders

Rash maculo-papular¹,^†

# participants affected / at risk

3/41 (7.32%)

0/34 (0.00%)

# events

Skin and subcutaneous tissue disorders

Skin fissures¹,^†

# participants affected / at risk

4/41 (9.76%)

1/34 (2.94%)

# events

Vascular disorders

Hypotension¹,^†

# participants affected / at risk

3/41 (7.32%)

0/41 (0.00%)

3/34 (8.82%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 19.0

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 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.

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 Part B, 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 Part B only.

Results Point of Contact

Name/Title:	Dr Karen So
Organization:	AstraZeneca
E-mail:	[email protected]

Documents available

StudyD5160C00013_redacted
Download
CSR_synopsis redacted
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Contact Backup

AstraZeneca Cancer Study Locator Service http://www.emergingmed.com/networks/astrazeneca

1-877-400-4656

astrazeneca@emergingmed.com

Investigators

Principal Investigator

Serban Ghiorghiu

AstraZeneca

Sponsors

Collaborators

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

StudyD5160C00013_redacted

CSR_synopsis redacted

Trial Results Summaries