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Drug-Drug Interaction Study With AZD9291 and Omeprazole in Healthy Volunteers

A Phase I, Fixed Sequence, Open-label, Study to Assess the Pharmacokinetics of AZD9291 in Healthy Male Volunteers When a Single Oral Dose of AZD9291 80 mg is Administered Alone and in Combination With Omeprazole

Status
Completed
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02224053
Enrollment
136
Registered
2014-08-25
Start date
2014-09-30
Completion date
2015-01-31
Last updated
2016-06-24

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

Conditions

Healthy Volunteer

Keywords

oncology, cancer, non small cell lung cancer, anticancer druge, omeprazole, healthy volunteer

Brief summary

This is a Phase 1, open-label, 2-period fixed sequence design to evaluate the interaction of AZD9291 with omeprazole in approximately 50 healthy, adult male volunteers. Volunteers will receive Treatment A (AZD9291 and omeprazole) in Period 1 and Treatment B (AZD9291 only) in Period 2. The dose of AZD9291 in Period 1 and the dose of AZD9291 in Period 2 will be separated by a washout of at least 21 days (the washout will not be more than 5 weeks). The study will be performed at up to 2 sites in the USA and will assess the effect of omeprazole (proton pump inhibitor) on AZD9291 exposure

Interventions

PROCEDUREPharmacokinetic sampling - AZD9291

Blood sampling to measure AZD9291

DRUGAZD9291 tablet dosing

AZD9291 80mg tablet taken on Day 5 in Period 1 and Day 1 in Period 2.

DRUGOmeprazole tablet dosing

Omeprzole taken from Days 1 to 5 in Period 1.

PROCEDUREPharmacokinetic sampling - AZ5140 and AZ7550

Blood samples to measure levels of AZ5140 and AZ7550

Sponsors

AstraZeneca
Lead SponsorINDUSTRY

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes

Inclusion criteria

For inclusion in the study volunteers must fulfil the following criteria. 1. Provision of signed and dated informed consent prior to any study-specific procedures. 2. Healthy male volunteers aged 18 to 55 years. (Healthy as determined by medical history, physical examination, laboratory parameters, ECG, and eye examination performed before the first administration of investigational product.) 3. Body mass index between 19 and 30 kg/m2, and body weight between 50 kg and 100 kg, inclusive. 4. Veins suitable for cannulation or repeated venepuncture. 5. Volunteers must be willing to use reliable methods of contraception (condom and spermicide), even if their partners are postmenopausal, surgically sterile, or using an effective hormonal method of contraception or intrauterine coil. In addition, volunteers must agree to continue to take similar contraceptive precautions and avoid sperm donation for 6 months after the last administration of AZD9291. Volunteers must not enter the study if any of the following

Exclusion criteria

are fulfilled: 1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca and Quintiles staff). 2. Previous enrollment in the present study. 3. History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the healthy volunteer at risk because of participation in the study, or influence the results or the healthy volunteer's ability to participate in the study. 4. History or presence of gastrointestinal, hepatic, or renal disease or surgical procedure or any other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs. 5. Any clinically significant abnormalities in physical examination, vital signs (supine blood pressure \>140 mmHg systolic, \>90 mmHg diastolic, or pulse rate ≤35 or ≥100 beats per minute), or clinical laboratory assessment as judged by the Investigator. 6. Acute illness, surgical procedures, or trauma from within 2 weeks before enrollment until first administration of investigational product (IP). 7. Volunteers who have received live or live-attenuated vaccine in the 2 weeks prior to dosing. 8. Volunteers with active malignancy or neoplastic disease in the previous 12 months. 9. A suspected/manifested infection according to International Airline Transportation Association (IATA) Categories A and B infectious substances. 10. Positive results on screening tests for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody, or human immunodeficiency virus (HIV). 11. Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG, as judged by the Investigator. 12. Known or suspected history of significant drug abuse as judged by the Investigator. 13. Positive screen for drugs of abuse or cotinine (nicotine level above 400 ng/mL) at screening or positive screen for alcohol, drugs of abuse, or cotinine on admission in Period 1 or Period 2. 14. History of alcohol abuse or excessive intake of alcohol, defined as regular weekly intake of greater than 21 units of alcohol in men (Note: 1 unit=25 mL spirits, 125 mL wine, or 250 mL beer or lager). 15. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to AZD9291, its excipients, or drugs with a similar chemical structure or class. 16. History of hypersensitivity to omeprazole, its excipients, or drugs with a similar chemical structure or class. 17. Use of any prescribed or nonprescribed medication, including drugs with hepatic enzyme-altering properties, such as St John's Wort, antacids, analgesics, herbal remedies, vitamins, and minerals during the 4 weeks (or longer depending on the medication's half-life) prior to the first administration of AZD9291 is not permitted. Occasional use of paracetamol (acetaminophen) and nonsteroidal nasal decongestant is permitted at the discretion of the Investigator. 18. 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 IP. 19. Blood donation within 1 month of screening or any blood donation/blood loss greater than 500 mL during the 3 months prior to screening. 20. Use of another new chemical entity (defined as a compound which has not been approved for marketing) or participation in any other clinical study (including methodology studies where no drugs were given) within 3 months of the first administration of IP in this study. 21. Current smokers or those who have smoked or used nicotine products within the previous 3 months. 22. Planned inpatient surgery, dental procedure, or hospitalisation during the study.

Design outcomes

Primary

MeasureTime frameDescription
AUC of AZD9291PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 doseArea under the plasma concentration-time curve from zero to infinity for AZD9291
Cmax of AZD9291PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.Rate and extent of absorption of AZD9291 following single oral doses of AZD9291 tablet formulation by assessment of maximum plasma concentration (Cmax).

Secondary

MeasureTime frameDescription
TmaxPK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using time to reach maximum plasma concentration, tmax
TlagPK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using lag time before observation of quantifiable analyte concentrations in plasma, tlag
t(1/2)PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using the terminal half-life, t(1/2)
λzPK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using the terminal rate constant, λz
CL/F of AZD9291PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.Assessment of the PK of AZD9291 using the apparent plasma clearance, CL/F
AUC(0-t)PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using area under the plasma concentration curve from zero extrapolated to o the time of the last quantifiable concentration, AUC(0-t)
Cmax of AZ5104 and AZ7550PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.Assessment of the PK of AZ5104 and AZ7550 (metabolites to AZD9291) using the maximum plasma concentration, Cmax
AUC of AZ5104 and AZ7550PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.Area under the plasma concentration-time curve from zero to infinity of AZ5104 and AZ7550 (metabolites to AZD9291)
Parent to Metabolite Ratios of AZ5104 and AZ7550 CmaxPK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.Assessment of the PK of AZ5104 and AZ7550 Cmax using the parent (AZD9291) to metabolite ratios
Parent to Metabolite Ratios of AZ5104 and AZ7550 AUCPK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.Assessment of the PK of AZ5104 and AZ7550 AUC using the parent (AZD9291) to metabolite ratios
Vz/F of AZD9291PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.Assessment of the PK of AZD9291 using the apparent volume of distribution, Vz/F
AUC(0-72)PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72 hours post AZD9291 dose.Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using area under the plasma concentration curve from time zero to 72 hours, AUC(0-72)

Countries

United States

Participant flow

Recruitment details

First subject enrolled: 3 September 2014 Last Subject Last Visit: 5 January 2015 Study was performed at 2 sites in the USA.

Pre-assignment details

136 subjects were enrolled (signed informed consent). Subjects were assigned to treatment if they met all the inclusion and none of the exclusion criteria. 68 subjects were enolled but failed inclusion/exclusion criteria and so were not eligible to be assigned treatment. The remaining 68 subjects started period 1 and received treatment.

Participants by arm

ArmCount
AZD9291 and Omeprazole
Sequential treatments periods of AZD9291 + omeprazole (including a washout) followed by AZD9291 alone.
68
Total68

Withdrawals & dropouts

PeriodReasonFG000
AZD9291 and Omeprazole Co-administrationAdverse Event3
AZD9291 and Omeprazole Co-administrationExceeding PK limits after Period 111
AZD9291 and Omeprazole Co-administrationProtocol non-compliance2
AZD9291 and Omeprazole Co-administrationProtocol Violation4
AZD9291 and Omeprazole Co-administrationWithdrawal by Subject1

Baseline characteristics

CharacteristicAZD9291 and Omeprazole
Age, Continuous34.0 Years
STANDARD_DEVIATION 11.08
Sex: Female, Male
Female
0 Participants
Sex: Female, Male
Male
68 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
8 / 682 / 47
serious
Total, serious adverse events
3 / 680 / 47

Outcome results

Primary

AUC of AZD9291

Area under the plasma concentration-time curve from zero to infinity for AZD9291

Time frame: PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose

Population: Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
AZD9291 and Omeprazole Co-administrationAUC of AZD92916690 nM.hFull Range 28.8
AZD9291 AloneAUC of AZD92916269 nM.hFull Range 37
Comparison: Study sized so experiment-wise power for the 90% CIs of geometric mean ratios for both AUC and Cmax of AZD9291 being within 80% to 125% was 90% (95% for each parameter). Within subject CV assumed to be 23%. 5% change in exposure also assumed.90% CI: [100.26, 113.46]
Primary

Cmax of AZD9291

Rate and extent of absorption of AZD9291 following single oral doses of AZD9291 tablet formulation by assessment of maximum plasma concentration (Cmax).

Time frame: PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.

Population: Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
AZD9291 and Omeprazole Co-administrationCmax of AZD9291127.8 nMFull Range 26.9
AZD9291 AloneCmax of AZD9291126.1 nMFull Range 31
Comparison: Study sized so experiment-wise power for the 90% CIs of geometric mean ratios for both AUC and Cmax of AZD9291 being within 80% to 125% was 90% (95% for each parameter). Within subject CV assumed to be 23%. 5% change in exposure also assumed.90% CI: [94.65, 109.16]
Secondary

AUC(0-72)

Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using area under the plasma concentration curve from time zero to 72 hours, AUC(0-72)

Time frame: PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72 hours post AZD9291 dose.

Population: Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product

ArmMeasureGroupValue (GEOMETRIC_MEAN)
AZD9291 and Omeprazole Co-administrationAUC(0-72)AZD92914404 nM.h
AZD9291 and Omeprazole Co-administrationAUC(0-72)AZ5104301.5 nM.h
AZD9291 and Omeprazole Co-administrationAUC(0-72)AZ7550216.5 nM.h
AZD9291 AloneAUC(0-72)AZD92914106 nM.h
AZD9291 AloneAUC(0-72)AZ5104304.0 nM.h
AZD9291 AloneAUC(0-72)AZ7550231.3 nM.h
Secondary

AUC(0-t)

Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using area under the plasma concentration curve from zero extrapolated to o the time of the last quantifiable concentration, AUC(0-t)

Time frame: PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.

Population: Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product

ArmMeasureGroupValue (GEOMETRIC_MEAN)
AZD9291 and Omeprazole Co-administrationAUC(0-t)AZD92916673 nM.h
AZD9291 and Omeprazole Co-administrationAUC(0-t)AZ5104546.5 nM.h
AZD9291 and Omeprazole Co-administrationAUC(0-t)AZ7550520.0 nM.h
AZD9291 AloneAUC(0-t)AZD92916249 nM.h
AZD9291 AloneAUC(0-t)AZ5104539.2 nM.h
AZD9291 AloneAUC(0-t)AZ7550560.0 nM.h
Secondary

AUC of AZ5104 and AZ7550

Area under the plasma concentration-time curve from zero to infinity of AZ5104 and AZ7550 (metabolites to AZD9291)

Time frame: PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.

Population: Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product

ArmMeasureGroupValue (GEOMETRIC_MEAN)Dispersion
AZD9291 and Omeprazole Co-administrationAUC of AZ5104 and AZ7550AZ5104556.6 nM.hFull Range 28.8
AZD9291 and Omeprazole Co-administrationAUC of AZ5104 and AZ7550AZ7750536.5 nM.h—
AZD9291 AloneAUC of AZ5104 and AZ7550AZ5104550.7 nM.hFull Range 37
AZD9291 AloneAUC of AZ5104 and AZ7550AZ7750574.9 nM.h—
Comparison: AZ510490% CI: [96.87, 108.07]
Comparison: AZ755090% CI: [89.92, 98.33]
Secondary

CL/F of AZD9291

Assessment of the PK of AZD9291 using the apparent plasma clearance, CL/F

Time frame: PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.

Population: Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product

ArmMeasureValue (GEOMETRIC_MEAN)
AZD9291 and Omeprazole Co-administrationCL/F of AZD929123.93 L/h
AZD9291 AloneCL/F of AZD929125.55 L/h
Secondary

Cmax of AZ5104 and AZ7550

Assessment of the PK of AZ5104 and AZ7550 (metabolites to AZD9291) using the maximum plasma concentration, Cmax

Time frame: PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.

Population: Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product

ArmMeasureGroupValue (GEOMETRIC_MEAN)Dispersion
AZD9291 and Omeprazole Co-administrationCmax of AZ5104 and AZ7550AZ51045.543 nMFull Range 26.9
AZD9291 and Omeprazole Co-administrationCmax of AZ5104 and AZ7550AZ75503.913 nM—
AZD9291 AloneCmax of AZ5104 and AZ7550AZ51045.889 nMFull Range 31
AZD9291 AloneCmax of AZ5104 and AZ7550AZ75504.402 nM—
Comparison: AZ510490% CI: [88.77, 101.21]
Comparison: AZ755090% CI: [83.89, 95.91]
Secondary

Parent to Metabolite Ratios of AZ5104 and AZ7550 AUC

Assessment of the PK of AZ5104 and AZ7550 AUC using the parent (AZD9291) to metabolite ratios

Time frame: PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.

Population: Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product

ArmMeasureGroupValue (GEOMETRIC_MEAN)
AZD9291 and Omeprazole Co-administrationParent to Metabolite Ratios of AZ5104 and AZ7550 AUCAZ51040.08318 Ratio
AZD9291 and Omeprazole Co-administrationParent to Metabolite Ratios of AZ5104 and AZ7550 AUCAZ75500.08019 Ratio
AZD9291 AloneParent to Metabolite Ratios of AZ5104 and AZ7550 AUCAZ51040.08785 Ratio
AZD9291 AloneParent to Metabolite Ratios of AZ5104 and AZ7550 AUCAZ75500.09166 Ratio
Secondary

Parent to Metabolite Ratios of AZ5104 and AZ7550 Cmax

Assessment of the PK of AZ5104 and AZ7550 Cmax using the parent (AZD9291) to metabolite ratios

Time frame: PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.

Population: Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product

ArmMeasureGroupValue (GEOMETRIC_MEAN)
AZD9291 and Omeprazole Co-administrationParent to Metabolite Ratios of AZ5104 and AZ7550 CmaxAZ51040.04335 Ratio
AZD9291 and Omeprazole Co-administrationParent to Metabolite Ratios of AZ5104 and AZ7550 CmaxAZ75500.03061 Ratio
AZD9291 AloneParent to Metabolite Ratios of AZ5104 and AZ7550 CmaxAZ51040.04671 Ratio
AZD9291 AloneParent to Metabolite Ratios of AZ5104 and AZ7550 CmaxAZ75500.03491 Ratio
Secondary

t(1/2)

Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using the terminal half-life, t(1/2)

Time frame: PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.

Population: Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product

ArmMeasureGroupValue (GEOMETRIC_MEAN)
AZD9291 and Omeprazole Co-administrationt(1/2)AZD929158.99 h
AZD9291 and Omeprazole Co-administrationt(1/2)AZ510451.06 h
AZD9291 and Omeprazole Co-administrationt(1/2)AZ755071.34 h
AZD9291 Alonet(1/2)AZD929163.60 h
AZD9291 Alonet(1/2)AZ510454.47 h
AZD9291 Alonet(1/2)AZ755072.16 h
Secondary

Tlag

Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using lag time before observation of quantifiable analyte concentrations in plasma, tlag

Time frame: PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.

Population: Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product

ArmMeasureGroupValue (MEDIAN)
AZD9291 and Omeprazole Co-administrationTlagAZD92910.00 h
AZD9291 and Omeprazole Co-administrationTlagAZ51040.00 h
AZD9291 and Omeprazole Co-administrationTlagAZ75500.00 h
AZD9291 AloneTlagAZD92910.00 h
AZD9291 AloneTlagAZ51040.00 h
AZD9291 AloneTlagAZ75500.00 h
Secondary

Tmax

Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using time to reach maximum plasma concentration, tmax

Time frame: PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.

Population: Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product

ArmMeasureGroupValue (MEDIAN)
AZD9291 and Omeprazole Co-administrationTmaxAZD92916 h
AZD9291 and Omeprazole Co-administrationTmaxAZ51048 h
AZD9291 and Omeprazole Co-administrationTmaxAZ755010 h
AZD9291 AloneTmaxAZD92916 h
AZD9291 AloneTmaxAZ51047 h
AZD9291 AloneTmaxAZ755010 h
Secondary

Vz/F of AZD9291

Assessment of the PK of AZD9291 using the apparent volume of distribution, Vz/F

Time frame: PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.

Population: Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product

ArmMeasureValue (GEOMETRIC_MEAN)
AZD9291 and Omeprazole Co-administrationVz/F of AZD92912037 L
AZD9291 AloneVz/F of AZD92912343 L
Secondary

λz

Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using the terminal rate constant, λz

Time frame: PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.

Population: Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product

ArmMeasureGroupValue (GEOMETRIC_MEAN)
AZD9291 and Omeprazole Co-administrationλzAZD92910.011748 1/h
AZD9291 and Omeprazole Co-administrationλzAZ51040.013577 1/h
AZD9291 and Omeprazole Co-administrationλzAZ75500.009718 1/h
AZD9291 AloneλzAZD92910.010898 1/h
AZD9291 AloneλzAZ51040.012722 1/h
AZD9291 AloneλzAZ75500.009606 1/h

Source: ClinicalTrials.gov · Data processed: Mar 3, 2026