Study to Assess the Effect of Rifampicin on Blood Levels... | NCT02197247

ID	Type	Description	Link
2014-001525-32	EudraCT Number

Label	Type	Description	Intervention Names
Rifampicin and AZD9291	Experimental	Sequential treatments of AZD9291 alone followed by AZD9291 +rifampicin, followed by AZD9291 alone.	Procedure: Pharmacokinetic sampling - AZD9291 Drug: Rifampicin Drug: AZD9291 tablet dosing Procedure: Pharmacokinetic sampling - rifampicin Procedure: Pharmacokinetic sampling - AZ5140 and AZ7550

Name	Type	Description	Arm Group Labels	Other Names
Pharmacokinetic sampling - AZD9291	Procedure	Blood sampling to measure AZD9291	Rifampicin and AZD9291

Measure	Description	Time Frame
Assessment of Maximum Plasma Concentration for AZD9291 After Dosing Alone and in Combination With Rifampicin (Css,Max)	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).	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.
Assessment of Area Under the Plasma Concentration-time Curve During the Dosing Interval for AZD9291 After Dosing Alone and in Combination With Rifampicin (AUCtau)	Rate and extent of absorption of AZD9291 by assessment of AUCtau. AZD9291 doses were first without, then with rifampicin (Periods 1 and 2, respectively).	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	Description	Time Frame
Assessment of Css,Max for AZD9291 Before and After Rifampicin	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).	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.

Eligibility Module

Eligibility Criteria

For inclusion in the study patient should fulfil the following criteria:

1. Male or female, aged at least 18 years. 2. Histological or cytological confirmation diagnosis of NSCLC. 3. Radiological documentation of disease progression while on a previous continuous treatment with an EGFR TKI, eg gefitinib, erlotinib or afatinib. In addition, other lines of therapy may have been given. All patients must have documented radiological progression on the last treatment administered prior to enrolling in the study.

4. Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q).

5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 with no deterioration over the previous 2 weeks (Appendix G).

6. Patients must have a life expectancy of ≥12 weeks as estimated at the time of screening.

7. Females should be using adequate contraceptive measures and must have a negative pregnancy test prior to start of dosing if of child-bearing potential, or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening: Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments. Women under 50 years old would be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution. Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, but not tubal ligation.

8. Male patients should be willing to use barrier contraception, ie, condoms, until 6 months after last study drug is taken.

9. Contact lens wearers must be prepared to not wear contact lenses and wear glasses for the duration of the rifampicin dosing.

Participation in another clinical study with an IP during the last 14 days (or a longer period depending on the defined characteristics of the agents used).
Treatment with any of the following: Treatment with an EGFR TKI (eg, erlotinib or gefitinib) w/in 8 days or approx. 5 x half-life, whichever is the longer, of the first dose of study treatment; any cytotoxic chemo, investigational agents or other anticancer drugs from a previous treatment regimen w/in 14 days of the first dose of study treatment; major surgery (excluding placement of vascular access) w/in 4 weeks of the first dose of study treatment; radiotherapy with a limited field of radiation for palliation w/in 1 week of the first dose of study treatment, with the exception of patients receiving radiation to more than 30% of bone marrow or with a wide field of radiation which must be completed w/in 4 weeks of the first; patients currently receiving (or unable to stop use prior to receiving the first dose) medications or herbal supplements known to be potent inhibitors of CYP3A4 (at least 1 week prior) and potent inducers of CYP3A4 (at least 3 week prior). All patients must avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer/inhibitory effects on CYP3A4.
Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy.
Any intake of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade, or other products containing grapefruit or Seville oranges within 7 days of the first administration of the IP until the final PK sample collection on Day 78 of Part A.
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 evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the Investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardise compliance with the protocol, or active infection including hepatitis B, hepatitis C and HIV. Screening for chronic conditions is not required.
Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: ANC <1.5 x 10^9/L; Platelet count <100 x 10^9/L; Haemoglobin <90 g/L; ALT >2.5 times the ULN if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases; AST >2.5 times ULN if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases; Total bilirubin >1.5 times ULN if no liver metastases or >3 times ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia) or liver metastases; creatinine >1.5 times ULN concurrent with creatinine clearance <50 ml/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is >1.5 times ULN.
Any of the following cardiac criteria: Mean resting corrected QT interval corrected for heart rate using Fridericia's correction factor (QTcF) >470 msec obtained from 3 electrocardiograms (ECGs); 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 >250 msec; 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.
Patients unable to swallow oral medication or patients with GI disorders or significant GI resection likely to interfere with the absorption of AZD9291.
Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
Women who are breastfeeding.
Patients with a known hypersensitivity to AZD9291 or rifampicin or any of the excipients of the products.
Concomitant medication contraindicated for use with rifampicin (including, but not limited to): cisapride, oral midazolam, nisoldipine, pimozide, quinidine, dofetilide, triazolam, levacetylmethadol (levomethadyl), 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA)-reductase inhibitors metabolised by CYP3A4, such as lovastatin and simvastatin, ergot alkaloids metabolised by CYP3A4, such as dihydroergotamine, ergometrine (ergonovine), ergotamine and methylergometrine (methylergonovine).
For optional genetic research: .Previous allogenic bone marrow transplant or Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection.

Name	Affiliation	Role
Serban Ghiorghiu, MSD	AstraZeneca	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Atlanta	Georgia	30322	United States
Research Site

PubMed Identifier	Type	Citation	Retractions
29381826	Derived	Vishwanathan K, Dickinson PA, So K, Thomas K, Chen YM, De Castro Carpeno J, Dingemans AC, Kim HR, Kim JH, Krebs MG, Chih-Hsin Yang J, Bui K, Weilert D, Harvey RD. The effect of itraconazole and rifampicin on the pharmacokinetics of osimertinib. Br J Clin Pharmacol. 2018 Jun;84(6):1156-1169. doi: 10.1111/bcp.13534. Epub 2018 Mar 23.

Label	URL
StudyD5160C00013\_redacted	View source

ID	Title	Description
FG000	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.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Assessment of Maximum Plasma Concentration for AZD9291 After Dosing Alone and in Combination With Rifampicin (Css,Max)

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).

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

nanomolar (nM)

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.

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG00038 OG00132

Title

Denominators

Categories

Title	Measurements
	OG000577.4± 44.7 OG001147.5± 48.2

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	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.					Geometric least-squares (LS) mean ratio	27.16			2-Sided	90	24.36	30.29			AZD9291+rifampicin / AZD9291 alone (Period 2 versus Period 1).		Non-Inferiority or Equivalence (legacy)

Primary

Assessment of Area Under the Plasma Concentration-time Curve During the Dosing Interval for AZD9291 After Dosing Alone and in Combination With Rifampicin (AUCtau)

Rate and extent of absorption of AZD9291 by assessment of AUCtau. AZD9291 doses were first without, then with rifampicin (Periods 1 and 2, respectively).

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

nM * hour (nM*h)

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.

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Assessment of Css,Max for AZD9291 Before and After Rifampicin

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).

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

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.

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Assessment of Css,Max for AZ5104 (Metabolite)

Rate and extent of absorption of AZ5104 (metabolite) by assessment of Css,max. AZD9291 dosing alone and in combination with rifampicin (all periods).

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

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.

ID	Title	Description
OG000	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.
OG001	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.
OG002

Secondary

Assessment of Css,Max for AZ7550 (Metabolite)

Rate and extent of absorption of AZ7550 (metabolite) by assessment of Css,max. AZD9291 dosing alone and in combination with rifampicin (all periods).

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

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.

ID	Title	Description
OG000	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.
OG001	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.
OG002

Secondary

Assessment of Css,Max for Rifampicin

Rate and extent of absorption of rifampicin by assessment of Css,max. AZD9291 dosing in combination with rifampicin (Period 2).

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

nanogram per millilitre (ng/mL)

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.

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Assessment of AUCtau for AZD9291 Before and After Rifampicin

Rate and extent of absorption of AZD9291 by assessment of AUCtau. AZD9291 alone before rifampicin (Period 1) and AZD9291 alone after rifampicin (Period 3).

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

nM*h

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.

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Assessment of AUCtau for AZ5104 (Metabolite)

Rate and extent of absorption of AZ5104 (metabolite) by assessment of AUCtau. AZD9291 dosing alone and in combination with rifampicin (all periods).

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

nM*h

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.

ID	Title	Description
OG000	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.
OG001	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.
OG002

Secondary

Assessment of AUCtau for AZ7550 (Metabolite)

Rate and extent of absorption of AZ7550 (metabolite) by assessment of AUCtau. AZD9291 dosing alone and in combination with rifampicin (all periods).

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

nM*h

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.

ID	Title	Description
OG000	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.
OG001	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.
OG002

Secondary

Assessment of AUCtau for Rifampicin

Rate and extent of absorption of rifampicin by assessment of AUCtau. AZD9291 dosing in combination with rifampicin (Period 2).

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*h/mL

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.

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Assessment of Tss,Max for AZD9291, and AZ5104 and AZ7550 (Metabolites)

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).

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.

Posted

Median

Full Range

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.

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Assessment of Tss,Max for Rifampicin

Rate and extent of absorption of rifampicin by assessment of tss,max. AZD9291 dosing in combination with rifampicin (Period 2).

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.

Posted

Median

Full Range

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.

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Assessment of Css,Min for AZD9291, and AZ5104 and AZ7550 (Metabolites)

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).

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

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.

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Assessment of Css,Min for Rifampicin

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).

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

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.

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Assessment of CLss/F for AZD9291

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).

Posted

Geometric Mean

Geometric Coefficient of Variation

Litre per hour (L/h)

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.

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Assessment of CLss/F for Rifampicin

Rate and extent of absorption of rifampicin by assessment of CLss/F. AZD9291 dosing in combination with rifampicin (Period 2).

Posted

Geometric Mean

Geometric Coefficient of Variation

L/h

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.

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Assessment of the Metabolic Ratios of Css,Max for AZ5104 and AZ7550 (MRCss,Max)

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).

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

Ratio

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.

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Assessment of the Metabolic Ratios of AUCtau for AZ5104 and AZ7550 (MRAUCtau)

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).

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

Ratio

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.

ID	Title	Description
OG000	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.
OG001	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.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrial fibrillation	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected41 at risk EG0021 events1 affected34 at risk
Influenza	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0002 events2 affected41 at risk EG0011 events1 affected41 at risk EG0021 events1 affected34 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0011 events1 affected41 at risk EG0020 events0 affected34 at risk
Ileus	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected41 at risk EG0021 events1 affected34 at risk
Malaise	General disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0011 events1 affected41 at risk EG0020 events0 affected34 at risk
Hepatitis B	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected41 at risk EG0021 events1 affected34 at risk
Pneumonia	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected41 at risk EG0021 events1 affected34 at risk
Pulmonary sepsis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected41 at risk EG0021 events1 affected34 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0011 events1 affected41 at risk EG0020 events0 affected34 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0011 events1 affected41 at risk EG0020 events0 affected34 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0011 events1 affected41 at risk EG0020 events0 affected34 at risk
Thrombotic stroke	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected41 at risk EG0021 events1 affected34 at risk
Thrombophlebitis	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0011 events1 affected41 at risk EG0020 events0 affected34 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 19.0	Systematic Assessment	EG0006 events6 affected41 at risk EG0013 events3 affected41 at risk EG0023 events3 affected34 at risk
Eye pruritus	Eye disorders	MedDRA 19.0	Systematic Assessment	EG0002 events2 affected41 at risk EG0010 events0 affected41 at risk EG0022 events2 affected34 at risk
Constipation	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG00010 events7 affected41 at risk EG0014 events4 affected41 at risk EG0026 events5 affected34 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG00039 events22 affected41 at risk EG00118 events14 affected41 at risk EG00221 events14 affected34 at risk
Oedema peripheral	General disorders	MedDRA 19.0	Systematic Assessment	EG0007 events7 affected41 at risk EG0014 events4 affected41 at risk EG0023 events3 affected34 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0006 events6 affected41 at risk EG0014 events4 affected41 at risk EG0022 events2 affected34 at risk
Weight decreased	Investigations	MedDRA 19.0	Systematic Assessment	EG0007 events7 affected41 at risk EG0013 events3 affected41 at risk EG0024 events4 affected34 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG00022 events19 affected41 at risk EG0018 events6 affected41 at risk EG00214 events13 affected34 at risk
Iron deficiency	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0002 events2 affected41 at risk EG0010 events0 affected41 at risk EG0022 events2 affected34 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 19.0	Systematic Assessment	EG0005 events3 affected41 at risk EG0012 events2 affected41 at risk EG0023 events2 affected34 at risk
Dry eye	Eye disorders	MedDRA 19.0	Systematic Assessment	EG0005 events4 affected41 at risk EG0013 events3 affected41 at risk EG0022 events2 affected34 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0006 events5 affected41 at risk EG0012 events2 affected41 at risk EG0024 events3 affected34 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0002 events2 affected41 at risk EG0010 events0 affected41 at risk EG0022 events2 affected34 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0003 events3 affected41 at risk EG0012 events2 affected41 at risk EG0021 events1 affected34 at risk
Nausea	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG00024 events13 affected41 at risk EG00114 events8 affected41 at risk EG00210 events9 affected34 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG00014 events10 affected41 at risk EG0016 events6 affected41 at risk EG0028 events6 affected34 at risk
Vomiting	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG00016 events11 affected41 at risk EG0017 events5 affected41 at risk EG0029 events7 affected34 at risk
Asthenia	General disorders	MedDRA 19.0	Systematic Assessment	EG0008 events7 affected41 at risk EG0015 events4 affected41 at risk EG0023 events3 affected34 at risk
Face oedema	General disorders	MedDRA 19.0	Systematic Assessment	EG0003 events3 affected41 at risk EG0012 events2 affected41 at risk EG0021 events1 affected34 at risk
Fatigue	General disorders	MedDRA 19.0	Systematic Assessment	EG00014 events13 affected41 at risk EG0019 events8 affected41 at risk EG0025 events5 affected34 at risk
Non-cardiac chest pain	General disorders	MedDRA 19.0	Systematic Assessment	EG0003 events3 affected41 at risk EG0011 events1 affected41 at risk EG0022 events2 affected34 at risk
Pyrexia	General disorders	MedDRA 19.0	Systematic Assessment	EG0006 events5 affected41 at risk EG0011 events1 affected41 at risk EG0025 events4 affected34 at risk
Folliculitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0002 events2 affected41 at risk EG0010 events0 affected41 at risk EG0022 events2 affected34 at risk
Influenza	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0002 events2 affected41 at risk EG0010 events0 affected41 at risk EG0022 events2 affected34 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0003 events3 affected41 at risk EG0012 events2 affected41 at risk EG0021 events1 affected34 at risk
Paronychia	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG00013 events8 affected41 at risk EG0012 events2 affected41 at risk EG00211 events6 affected34 at risk
Urinary tract infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG00012 events6 affected41 at risk EG0016 events6 affected41 at risk EG0026 events2 affected34 at risk
Alanine aminotransferase increased	Investigations	MedDRA 19.0	Systematic Assessment	EG0004 events3 affected41 at risk EG0011 events1 affected41 at risk EG0023 events2 affected34 at risk
Blood creatinine increased	Investigations	MedDRA 19.0	Systematic Assessment	EG0004 events3 affected41 at risk EG0011 events1 affected41 at risk EG0023 events2 affected34 at risk
Electrocardiogram QT prolonged	Investigations	MedDRA 19.0	Systematic Assessment	EG0003 events3 affected41 at risk EG0010 events0 affected41 at risk EG0023 events3 affected34 at risk
Neutrophil count decreased	Investigations	MedDRA 19.0	Systematic Assessment	EG0006 events3 affected41 at risk EG0013 events2 affected41 at risk EG0023 events2 affected34 at risk
Platelet count decreased	Investigations	MedDRA 19.0	Systematic Assessment	EG0007 events5 affected41 at risk EG0013 events2 affected41 at risk EG0024 events4 affected34 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0003 events3 affected41 at risk EG0012 events2 affected41 at risk EG0021 events1 affected34 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0002 events2 affected41 at risk EG0010 events0 affected41 at risk EG0022 events2 affected34 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0006 events5 affected41 at risk EG0013 events3 affected41 at risk EG0023 events3 affected34 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG00017 events11 affected41 at risk EG0018 events6 affected41 at risk EG0029 events5 affected34 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0002 events2 affected41 at risk EG0010 events0 affected41 at risk EG0022 events2 affected34 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0002 events2 affected41 at risk EG0010 events0 affected41 at risk EG0022 events2 affected34 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG00011 events9 affected41 at risk EG0016 events4 affected41 at risk EG0025 events5 affected34 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0003 events3 affected41 at risk EG0011 events1 affected41 at risk EG0022 events2 affected34 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0005 events4 affected41 at risk EG0013 events2 affected41 at risk EG0022 events2 affected34 at risk
Dizziness	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0003 events3 affected41 at risk EG0010 events0 affected41 at risk EG0023 events3 affected34 at risk
Headache	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG00013 events8 affected41 at risk EG00110 events7 affected41 at risk EG0023 events2 affected34 at risk
Insomnia	Psychiatric disorders	MedDRA 19.0	Systematic Assessment	EG0003 events3 affected41 at risk EG0012 events2 affected41 at risk EG0021 events1 affected34 at risk
Haematuria	Renal and urinary disorders	MedDRA 19.0	Systematic Assessment	EG0003 events3 affected41 at risk EG0012 events2 affected41 at risk EG0021 events1 affected34 at risk
Pollakiuria	Renal and urinary disorders	MedDRA 19.0	Systematic Assessment	EG0003 events3 affected41 at risk EG0013 events3 affected41 at risk EG0020 events0 affected34 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG00012 events10 affected41 at risk EG0017 events7 affected41 at risk EG0025 events4 affected34 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0007 events5 affected41 at risk EG0014 events3 affected41 at risk EG0023 events2 affected34 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0004 events4 affected41 at risk EG0013 events3 affected41 at risk EG0021 events1 affected34 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG0002 events2 affected41 at risk EG0010 events0 affected41 at risk EG0022 events2 affected34 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG0003 events3 affected41 at risk EG0012 events2 affected41 at risk EG0021 events1 affected34 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG00027 events17 affected41 at risk EG00112 events10 affected41 at risk EG00215 events12 affected34 at risk
Nail discolouration	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG0002 events2 affected41 at risk EG0010 events0 affected41 at risk EG0022 events2 affected34 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG0008 events6 affected41 at risk EG0014 events4 affected41 at risk EG0024 events4 affected34 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG0003 events3 affected41 at risk EG0013 events3 affected41 at risk EG0020 events0 affected34 at risk
Skin fissures	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG0007 events4 affected41 at risk EG0014 events4 affected41 at risk EG0023 events1 affected34 at risk
Hypotension	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0003 events3 affected41 at risk EG0010 events0 affected41 at risk EG0023 events3 affected34 at risk

ID	Term
D002289	Carcinoma, Non-Small-Cell Lung
D009369	Neoplasms

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
D012294	Rifamycins
D006576	Heterocyclic Compounds, 4 or More Rings
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D047029	Lactams, Macrocyclic
D047028	Macrocyclic Compounds
D011083	Polycyclic Compounds

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Overall	Parts A and B of the study combined.	11	41	40	41
EG001	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.	7	41	39	41
EG002	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.	6	34	34	34