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Omeprazole

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Sequential treatments of AZD9291 + omeprazole followed by AZD9291 alone, with a washout period in between.

Pharmacokinetic sampling - AZD9291

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

AZD9291 tablet dosing

Omeprzole taken from Days 1 to 5 in Period 1.

Omeprazole tablet dosing

Blood samples to measure levels of AZ5140 and AZ7550

Pharmacokinetic sampling - AZ5140 and AZ7550

Serban Ghiorghiu, MSD

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

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

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

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

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)

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)

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

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

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

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

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

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

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

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

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

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

AstraZeneca

Once daily dosing of omeprazole 40 mg on Days 1 to 5 and AZD9291 80 mg single oral dose on Day 5 (Period 1).

AZD9291 and Omeprazole Co-administration

AZD9291 80 mg single oral dose on Day 1 (Period 2)

AZD9291 Alone

Sequential treatments periods of AZD9291 + omeprazole (including a washout) followed by AZD9291 alone.

AZD9291 and Omeprazole

Age, Continuous

Sex: Female, Male

Dr Karen So

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.

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Drug-Drug Interaction Study With AZD9291 and Omeprazole in Healthy Volunteers	NCT02224053	Healthy Volunte...	Pharmacokinetic... AZD9291 tablet ... Omeprazole tabl... Pharmacokinetic...	18 Years - 55 Years	AstraZeneca
Drug-Drug Interaction Study With AZD9291 and Omeprazole in Healthy Volunteers	NCT02224053	Healthy Volunte...	Pharmacokinetic... AZD9291 tablet ... Omeprazole tabl... Pharmacokinetic...	18 Years - 55 Years	AstraZeneca

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