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Study to Assess the Effect of Itraconazole (a CYP3A4 Inhibitor) on the Pharmacokinetics of AZD9291, in Patients With EGFR Positive Non-small Cell Lung Cancer. Patients Will be Chosen From Those Who Have Already Been Prescribed an EGFR TKI Medicine (Such as Iressa or Tarceva)

A Phase I, Open-label, Non-randomised Study to Assess the Effect of Itraconazole (a CYP3A4 Inhibitor) on the Pharmacokinetics of a Single Oral Dose of AZD9291 in Patients With EGFRm Positive NSCLC Whose Disease Has Progressed on an EGFR TKI

Status
Completed
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02157883
Enrollment
39
Registered
2014-06-06
Start date
2014-11-06
Completion date
2023-05-17
Last updated
2025-11-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Advanced Non Small Cell Lung Cancer, Advanced (Inoperable) Non Small Cell Lung Cancer

Keywords

oncology, cancer, non small cell lung cancer, anticancer drug, pharmacokinetics, AZD9291, intraconazole, EGFR sensitivity mutation

Brief summary

This is a 2 part study in patients with EGFRm+ non small cell lung cancer (NSCLC), whose disease has progressed on an EGFRm TKI, who are refractory or resistant to standard therapy. Part A will assess the effect of multiple oral doses of itraconazole on the single dose pharmacokinetic (PK) parameters of AZD9291. On completion of Part A, patients may continue to take AZD9291 tablets (Part B) following the collection of the 216 hour sample on Day 19 if they and the Investigator deem it appropriate, until such time as their disease progresses, the Investigator believes they are no longer deriving clinical benefit, or they stop taking AZD9291 for any other reason

Interventions

PROCEDUREPharmacokinetic sampling

Blood samples taken pre and post dosing with AZD9291+/- itraconazole

DRUGAZD9291

AZD9291 tablets: Part A 80mg od, days 1 and 10 only. Part B 80mg od for 12 months.

DRUGItraconazole

Itraconazole tablets: 2x100mg bd, Part A days 6 to 19 only

Sponsors

AstraZeneca
Lead SponsorINDUSTRY

Study design

Allocation
NON_RANDOMIZED
Primary purpose
OTHER
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No

Inclusion criteria

For inclusion in the study, patients 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 or erlotinib. 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. ECOG performance status 0-1 with no deterioration over the previous 2 weeks. 6. Patients must have a life expectancy of ≥12 weeks as estimated at the time of screening. 7. Evidence of non-childbearing status for women of childbearing potential, or post-menopausal status: negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on Day 1 of Part A, or post menopausal status. 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 consider postmenopausal 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. Patients should not enter the study if any of the following

Exclusion criteria

are fulfilled: 1. 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). 2. Treatment with any of the following: Treatment with an EGFR TKI w/in 8 days or approximately 5x half-life, whichever is the longer, of the first dose of study treatment; Any cytotoxic chemotherapy, investigational agents or other anticancer drugs w/in 14 days of the first dose of study treatment; Major surgery (excluding placement of vascular access) within 4 weeks of the first dose; Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of study treatment, with the exception of patients receiving radiation to more than 30% of the bone marrow or with a wide field of radiation which must be completed within 4 weeks of the first dose of study treatment; Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inhibitors of CYP2C8 and of CYP3A4 (at least 1 week prior) and potent inducers of CYP3A4 (at least 3 week prior). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer/inhibitory effects on CYP3A4, CYP2C8, and/ or CYP1A2. 3. 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. 4. 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 end of Part A. 5. Spinal cord compression or brain metastases unless asymptomatic, stable and not requiring steroids for at least 4 weeks prior to start of study treatment. 6. 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 human immunodeficiency virus (HIV). Screening for chronic conditions is not required. 7. 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 x the institutional ULN if no demonstrable liver metastases or \>5 x institutional ULN in the presence of liver metastases; AST \>2.5 x institutional ULN if no demonstrable liver metastases or \>5 x institutional ULN in the presence of liver metastases; Total bilirubin \>1.5 x institutional ULN if no liver metastases or \>3 x institutional ULN in the presence of documented Gilbert's Syndrome or liver metastases; Creatinine \>1.5 x institutional ULN concurrent with creatinine clearance \<50 mL/min (measured or calculated by Cockcroft-Gault formula); confirmation of creatinine clearance is only required when creatinine is \>1.5 x institutional ULN. 8. Any of the following cardiac criteria: Mean resting corrected QT interval corrected for heart rate using Fridericia's correction factor (QTcF) \>450 msec obtained from 3 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. 9. Patients unable to swallow oral medication or patients with GI disorders or significant GI resection likely to interfere with the absorption of AZD9291. 10. Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD. 11. Women who are breastfeeding. 12. Patients with a known hypersensitivity to AZD9291 or itranconazole or any of their excipients. 12\. Concomitant medication contraindicated for use with itraconazole (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 metabolized by CYP3A4, such as lovastatin and simvastatin, ergot alkaloids metabolized by CYP3A4, such as dihydroergotamine, ergometrine (ergonovine), ergotamine and methylergometrine (methylergonovine). 13\. For optional genetic research: Previous allogenic bone marrow transplant or non-leukocyte depleted whole blood transfusion within 120 days of sample collection.

Design outcomes

Primary

MeasureTime frameDescription
Cmax of AZD9291Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.Pharmacokinetics of AZD9291 by assessment of maximum plasma AZD9291 concentration
AUC of AZD9291Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.Pharmacokinetics of AZD9291 by assessment of area under the plasma concentration time curve from zero to infinity

Secondary

MeasureTime frameDescription
AUC(0-t) of AZD9291Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.Pharmacokinetics of AZD9291 by assessment of area under the plasma concentration curve from time zero to last quantifiable dose
Tmax of AZD9291Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.Pharmacokinetics of AZD9291 by assessment of time to Cmax
CL/F of AZD9291Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.Rate and extent of absorption of AZD9291 by assessment of apparent clearance following oral administration
Vz/F of AZD9291Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.Rate and extent of absorption of AZD9291 by assessment of the apprarent volume of distribution
t1/2 of AZD9291Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.Pharmacokinetics of AZD9291 by assessment of the terminal half-life
AUC of AZ5104Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.Pharmacokinetics of AZ5104 (metabolite to AZD9291) by assessment of area under the plasma concentration time curve from zero to infinity
Cmax of AZ7550Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.Pharmacokinetics of AZ7550 (metabolite to AZD9291) by assessment of maximum plasma AZ7550 concentration
AUC of AZ7550Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.Pharmacokinetics of AZ7550 (metabolite to AZD9291) by assessment of area under the plasma concentration time curve from zero to infinity
Cmax of AZ5104Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.Pharmacokinetics of AZ5104 (metabolite to AZD9291) by assessment of maximum plasma AZ5104 concentration
AUC(0-120) of AZD9291Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.Pharmacokinetics of AZD9291 by assessment of area under the plasma concentration time curve from zero to 120 hours

Countries

Belgium, Netherlands, South Korea, Taiwan, United Kingdom, United States

Participant flow

Recruitment details

First subject enrolled: 6 November 2014; Last Subject Last Visit Part A: 3 April 2015 and Part B: 31 March 2016. Study performed at 15 sites across Asia, North America and Western Europe. Part A assessed effect of multiple doses of itraconazole on PK of AZD9291; Part B allowed subjects further access to AZD9291 and provided additional safety data.

Pre-assignment details

The 39 patients started Period 1 and received treatment.

Participants by arm

ArmCount
AZD9291 and Itraconozole (Part A); AZD9291 Alone (Part B)
In Part A of the study, sequential treatments of AZD9291 alone (including a washout) followed by AZD9291+itraconazole. Each patient received single 80 mg oral doses of AZD9291 tablets on Days 1 and 10, and in addition received itraconazole capsules 200 mg twice daily on Days 6 to 18. In Part B of the study, each patient received 80 mg oral AZD9291 tablet formulation once daily, for the duration of their participation.
39
Total39

Withdrawals & dropouts

PeriodReasonFG000
Part A: Day 6-18 (AZD9291+Itraconozole)Adverse Event1
Part B: Day 19 to End Part B (AZD9291)Adverse Event3
Part B: Day 19 to End Part B (AZD9291)Death3
Part B: Day 19 to End Part B (AZD9291)Disease progression15
Part B: Day 19 to End Part B (AZD9291)Withdrawal by Subject1

Baseline characteristics

CharacteristicAZD9291 and Itraconozole (Part A); AZD9291 Alone (Part B)
Age, Continuous58.8 years
STANDARD_DEVIATION 10.73
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
Race (NIH/OMB)
Asian
29 Participants
Race (NIH/OMB)
Black or African American
0 Participants
Race (NIH/OMB)
More than one race
0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
Race (NIH/OMB)
White
10 Participants
Sex: Female, Male
Female
27 Participants
Sex: Female, Male
Male
12 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —
other
Total, other adverse events
39 / 3924 / 3938 / 38
serious
Total, serious adverse events
12 / 393 / 399 / 38

Outcome results

Primary

AUC of AZD9291

Pharmacokinetics of AZD9291 by assessment of area under the plasma concentration time curve from zero to infinity

Time frame: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.

Population: All patients who received at least 1 dose of AZD9291 and had sufficient postdose PK assessments to determine outcome measure without important protocol deviations/violations and excluding Period 2 data for patients meeting carry-over exclusion criterion (defined as Period 2 pre-dose concentration \>10% of Cmax).

ArmMeasureValue (GEOMETRIC_MEAN)
AZD9291 AloneAUC of AZD929113520 nM*h
AZD9291+ItraconazoleAUC of AZD929117090 nM*h
Comparison: Study sized so experiment-wise power for the upper bound of the 90% CIs of geometric mean ratios for both AUC and Cmax of AZD9291 being below 200% was 90% (95% for each parameter). Within patient CV assumed to be 34%. A 50% increase in exposure was also assumed.90% CI: [114.61, 134.53]
Primary

Cmax of AZD9291

Pharmacokinetics of AZD9291 by assessment of maximum plasma AZD9291 concentration

Time frame: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.

Population: All patients who received at least 1 dose of AZD9291 and had sufficient postdose PK assessments to determine outcome measure without important protocol deviations/violations and excluding Period 2 data for patients meeting carry-over exclusion criterion (defined as Period 2 pre-dose concentration \>10% of Cmax).

ArmMeasureValue (GEOMETRIC_MEAN)
AZD9291 AloneCmax of AZD9291242.5 nM
AZD9291+ItraconazoleCmax of AZD9291201.7 nM
Comparison: Study sized so experiment-wise power for the upper bound of the 90% CIs of geometric mean ratios for both AUC and Cmax of AZD9291 being below 200% was 90% (95% for each parameter). Within patient CV assumed to be 34%. A 50% increase in exposure was also assumed.90% CI: [73.15, 87.21]
Secondary

AUC(0-120) of AZD9291

Pharmacokinetics of AZD9291 by assessment of area under the plasma concentration time curve from zero to 120 hours

Time frame: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.

Population: All patients who received at least 1 dose of AZD9291 and had sufficient postdose PK assessments to determine outcome measure without important protocol deviations/violations and excluding Period 2 data for patients meeting carry-over exclusion criterion (defined as Period 2 pre-dose concentration \>10% of Cmax).

ArmMeasureValue (GEOMETRIC_MEAN)
AZD9291 AloneAUC(0-120) of AZD929110280 nM*h
AZD9291+ItraconazoleAUC(0-120) of AZD929111370 nM*h
Secondary

AUC(0-t) of AZD9291

Pharmacokinetics of AZD9291 by assessment of area under the plasma concentration curve from time zero to last quantifiable dose

Time frame: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.

Population: All patients who received at least 1 dose of AZD9291 and had sufficient postdose PK assessments to determine outcome measure without important protocol deviations/violations and excluding Period 2 data for patients meeting carry-over exclusion criterion (defined as Period 2 pre-dose concentration \>10% of Cmax).

ArmMeasureValue (GEOMETRIC_MEAN)
AZD9291 AloneAUC(0-t) of AZD929112260 nM*h
AZD9291+ItraconazoleAUC(0-t) of AZD929114520 nM*h
Secondary

AUC of AZ5104

Pharmacokinetics of AZ5104 (metabolite to AZD9291) by assessment of area under the plasma concentration time curve from zero to infinity

Time frame: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.

Population: All patients who received at least 1 dose of AZD9291 and had sufficient postdose PK assessments to determine outcome measure without important protocol deviations/violations and excluding Period 2 data for patients meeting carry-over exclusion criterion (defined as Period 2 pre-dose AZ5104 concentration \>20% of Cmax).

ArmMeasureValue (GEOMETRIC_MEAN)
AZD9291 AloneAUC of AZ51041155 nM*h
AZD9291+ItraconazoleAUC of AZ5104941.4 nM*h
Comparison: Study sized so experiment-wise power for the upper bound of the 90% CIs of geometric mean ratios for both AUC and Cmax of AZD9291 being below 200% was 90% (95% for each parameter). Within patient CV assumed to be 34%. A 50% increase in exposure was also assumed.90% CI: [94.36, 124.19]
Secondary

AUC of AZ7550

Pharmacokinetics of AZ7550 (metabolite to AZD9291) by assessment of area under the plasma concentration time curve from zero to infinity

Time frame: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.

Population: All patients who received at least 1 dose of AZD9291 and had sufficient postdose PK assessments to determine outcome measure without important protocol deviations, where AUC possible to calculate, and including Period 2 data (all patients met carry over criteria of Period 2 pre-dose AZ7550 concentration \>20% of Cmax).

ArmMeasureValue (GEOMETRIC_MEAN)
AZD9291 AloneAUC of AZ7550624.1 nM*h
AZD9291+ItraconazoleAUC of AZ7550292.1 nM*h
Comparison: Study sized so experiment-wise power for the upper bound of the 90% CIs of geometric mean ratios for both AUC and Cmax of AZD9291 being below 200% was 90% (95% for each parameter). Within patient CV assumed to be 34%. A 50% increase in exposure was also assumed.90% CI: [43.7, 54.99]
Secondary

CL/F of AZD9291

Rate and extent of absorption of AZD9291 by assessment of apparent clearance following oral administration

Time frame: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.

Population: All patients who received at least 1 dose of AZD9291 and had sufficient postdose PK assessments to determine outcome measure without important protocol deviations/violations and excluding Period 2 data for patients meeting carry-over exclusion criterion (defined as Period 2 pre-dose concentration \>10% of Cmax).

ArmMeasureValue (GEOMETRIC_MEAN)
AZD9291 AloneCL/F of AZD929111.84 L/h
AZD9291+ItraconazoleCL/F of AZD92919.368 L/h
Secondary

Cmax of AZ5104

Pharmacokinetics of AZ5104 (metabolite to AZD9291) by assessment of maximum plasma AZ5104 concentration

Time frame: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.

Population: All patients who received at least 1 dose of AZD9291 and had sufficient postdose PK assessments to determine outcome measure without important protocol deviations/violations and excluding Period 2 data for patients meeting carry-over exclusion criterion (defined as Period 2 pre-dose AZ5104 concentration \>20% of Cmax).

ArmMeasureValue (GEOMETRIC_MEAN)
AZD9291 AloneCmax of AZ51048.568 nM
AZD9291+ItraconazoleCmax of AZ51045.746 nM
Comparison: Study sized so experiment-wise power for the upper bound of the 90% CIs of geometric mean ratios for both AUC and Cmax of AZD9291 being below 200% was 90% (95% for each parameter). Within patient CV assumed to be 34%. A 50% increase in exposure was also assumed.90% CI: [64.18, 89.69]
Secondary

Cmax of AZ7550

Pharmacokinetics of AZ7550 (metabolite to AZD9291) by assessment of maximum plasma AZ7550 concentration

Time frame: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.

Population: All patients who received at least 1 dose of AZD9291 and had sufficient postdose PK assessments to determine outcome measure without important protocol deviations/violations and including Period 2 data (since all patients met carry over criteria of Period 2 pre-dose AZ7550 concentration \>20% of Cmax).

ArmMeasureValue (GEOMETRIC_MEAN)
AZD9291 AloneCmax of AZ75504.321 nM
AZD9291+ItraconazoleCmax of AZ75501.897 nM
Comparison: Study sized so experiment-wise power for the upper bound of the 90% CIs of geometric mean ratios for both AUC and Cmax of AZD9291 being below 200% was 90% (95% for each parameter). Within patient CV assumed to be 34%. A 50% increase in exposure was also assumed.90% CI: [39.94, 49.21]
Secondary

t1/2 of AZD9291

Pharmacokinetics of AZD9291 by assessment of the terminal half-life

Time frame: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.

Population: All patients who received at least 1 dose of AZD9291 and had sufficient postdose PK assessments to determine outcome measure without important protocol deviations/violations and excluding Period 2 data for patients meeting carry-over exclusion criterion (defined as Period 2 pre-dose concentration \>10% of Cmax).

ArmMeasureValue (GEOMETRIC_MEAN)
AZD9291 Alonet1/2 of AZD929161.05 hours
AZD9291+Itraconazolet1/2 of AZD929178.36 hours
Secondary

Tmax of AZD9291

Pharmacokinetics of AZD9291 by assessment of time to Cmax

Time frame: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.

Population: All patients who received at least 1 dose of AZD9291 and had sufficient postdose PK assessments to determine outcome measure without important protocol deviations/violations and excluding Period 2 data for patients meeting carry-over exclusion criterion (defined as Period 2 pre-dose concentration \>10% of Cmax).

ArmMeasureValue (MEDIAN)
AZD9291 AloneTmax of AZD92914.00 hours
AZD9291+ItraconazoleTmax of AZD92916.04 hours
Secondary

Vz/F of AZD9291

Rate and extent of absorption of AZD9291 by assessment of the apprarent volume of distribution

Time frame: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.

Population: All patients who received at least 1 dose of AZD9291 and had sufficient postdose PK assessments to determine outcome measure without important protocol deviations/violations and excluding Period 2 data for patients meeting carry-over exclusion criterion (defined as Period 2 pre-dose concentration \>10% of Cmax).

ArmMeasureValue (GEOMETRIC_MEAN)
AZD9291 AloneVz/F of AZD92911019 L
AZD9291+ItraconazoleVz/F of AZD92911059 L

Source: ClinicalTrials.gov · Data processed: Mar 7, 2026