Clinical trial NCT02224053: Drug-Drug Interaction Study With AZD9291 and Omeprazole in Healthy Volunteers
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Keywords: oncology, cancer, non small cell lung cancer, anticancer druge, omeprazole, healthy volunteer
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2014-08-25
Enrollment: 136
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility 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.

Primary outcomes:
measure: AUC of AZD9291
timeFrame: 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
measure: Cmax of AZD9291
timeFrame: 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:
measure: AUC(0-t)
timeFrame: 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.
measure: AUC(0-72)
timeFrame: 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.
measure: Tmax
timeFrame: 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.
measure: Tlag
timeFrame: 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.
measure: t(1/2)
timeFrame: 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.
measure: λz
timeFrame: 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.
measure: CL/F of AZD9291
timeFrame: 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.
measure: Vz/F of AZD9291
timeFrame: 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.
measure: Cmax of AZ5104 and AZ7550
timeFrame: 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.
measure: AUC of AZ5104 and AZ7550
timeFrame: 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.
measure: Parent to Metabolite Ratios of AZ5104 and AZ7550 Cmax
timeFrame: 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.
measure: Parent to Metabolite Ratios of AZ5104 and AZ7550 AUC
timeFrame: 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.
Other outcomes:
Locations:
city: Overland Park
country: United States
facility: Research Site
state: Kansas
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
Study officials:
affiliation: AstraZeneca
name: Serban Ghiorghiu, MSD
role: STUDY_DIRECTOR
References:
citation: 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.