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

NCT02224053 | Completed Phase 1 Results

• 1 other identifier: D5160C00010
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 2

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

Conditions

Healthy Volunteer

Keywords

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

Outcome Measures

Primary Outcomes (2)

• AUC of AZD9291

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

  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

• 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).

  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.

Secondary Outcomes (12)

• 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.

• 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.

• Tmax

  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.

• Tlag

  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.

• 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.

Study Arms (1)

AZD9291 and omeprazole

EXPERIMENTAL

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

Procedure: Pharmacokinetic sampling - AZD9291; Drug: AZD9291 tablet dosing; Drug: Omeprazole tablet dosing; Procedure: Pharmacokinetic sampling - AZ5140 and AZ7550

Interventions

Pharmacokinetic sampling - AZD9291 PROCEDURE

Blood sampling to measure AZD9291

AZD9291 and omeprazole

AZD9291 tablet dosing DRUG

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

AZD9291 and omeprazole

Omeprazole tablet dosing DRUG

Omeprzole taken from Days 1 to 5 in Period 1.

AZD9291 and omeprazole

Pharmacokinetic sampling - AZ5140 and AZ7550 PROCEDURE

Blood samples to measure levels of AZ5140 and AZ7550

AZD9291 and omeprazole

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca and Quintiles staff).
• Previous enrollment in the present study.
• 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.
• 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.
• 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.
• Acute illness, surgical procedures, or trauma from within 2 weeks before enrollment until first administration of investigational product (IP).
• Volunteers who have received live or live-attenuated vaccine in the 2 weeks prior to dosing.
• Volunteers with active malignancy or neoplastic disease in the previous 12 months.
• A suspected/manifested infection according to International Airline Transportation Association (IATA) Categories A and B infectious substances.
• Positive results on screening tests for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody, or human immunodeficiency virus (HIV).
• Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG, as judged by the Investigator.
• Known or suspected history of significant drug abuse as judged by the Investigator.
• 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.
• 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).
• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (2)

Research Site

Overland Park, Kansas, United States

Location

Research Site

Minneapolis, Minnesota, United States

Location

Related Publications (1)

• Vishwanathan K, Dickinson PA, Bui K, Cassier PA, Greystoke A, Lisbon E, Moreno V, So K, Thomas K, Weilert D, Yap TA, Plummer R. The Effect of Food or Omeprazole on the Pharmacokinetics of Osimertinib in Patients With Non-Small-Cell Lung Cancer and in Healthy Volunteers. J Clin Pharmacol. 2018 Apr;58(4):474-484. doi: 10.1002/jcph.1035. Epub 2017 Nov 26.

  PMID: 29178442 DERIVED

MeSH Terms

Conditions

Neoplasms; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Dr Karen So
• Organization: AstraZeneca

ClinicalTrialTransparency@astrazeneca.com

Study Officials

• Serban Ghiorghiu, MSD

  AstraZeneca

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2014
• First Posted: August 25, 2014
• Study Start: September 1, 2014
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: June 24, 2016
• Results First Posted: December 31, 2015

Record last verified: 2016-05

Locations

US (2)