A Study to Evaluate the Effects of Food and Esomeprazole on the Pharmacokinetics of Crizotinib in a Coated Microsphere Formulation.

NCT ID: NCT03137134

Last Updated: 2017-10-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-06-20

Study Completion Date

2017-10-17

Brief Summary

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This study will estimate the effect of food and the proton pump inhibitor, esomeprazole on the pharmacokinetics of crizotinib in a coated microsphere formulation.

Detailed Description

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This study is an open-label, randomized, 4-period, 5-treatment, 6-sequence study in adult healthy volunteers. Subjects will receive up to four separate single oral 300 mg doses of a coated microsphere (cMS) formulation of crizotinib. Period 1 through Period 3 will evaluate the effect of food, and, the effect of multiple doses of a gastrointestinal acid reducing agent, esomeprazole, in fasted state, on the pharmacokinetics (PK) of crizotinib cMS. Period 4 will evaluate whether apple sauce or orange juice may reduce the effect of multiple doses of esomeprazole on the PK of crizotinib cMS, if there is an effect.

Conditions

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Healthy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Open-label

Study Groups

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Treatment A

(reference) Crizotinib cMS 300 mg in fasted state

Group Type ACTIVE_COMPARATOR

Crizotinib

Intervention Type DRUG

Crizotinib in a coated microsphere formulation

Treatment B

(test) Crizotinib cMS 300 mg in fed state

Group Type EXPERIMENTAL

Crizotinib

Intervention Type DRUG

Crizotinib in a coated microsphere formulation

Treatment C

(test) 5 days of esomeprazole 40 mg followed by crizotinib cMS 300 mg in fasted state

Group Type EXPERIMENTAL

Crizotinib

Intervention Type DRUG

Crizotinib in a coated microsphere formulation

Esomeprazole

Intervention Type DRUG

Proton pump inhibitor, esomeprazole

Treatment D

(test) 5 days of esomeprazole 40 mg followed by crizotinib cMS 300 mg with apple sauce.

Group Type EXPERIMENTAL

Crizotinib

Intervention Type DRUG

Crizotinib in a coated microsphere formulation

Esomeprazole

Intervention Type DRUG

Proton pump inhibitor, esomeprazole

Treatment E

(test) 5 days of esomeprazole 40 mg followed by crizotinib cMS 300 mg with orange juice

Group Type EXPERIMENTAL

Crizotinib

Intervention Type DRUG

Crizotinib in a coated microsphere formulation

Esomeprazole

Intervention Type DRUG

Proton pump inhibitor, esomeprazole

Interventions

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Crizotinib

Crizotinib in a coated microsphere formulation

Intervention Type DRUG

Esomeprazole

Proton pump inhibitor, esomeprazole

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Healthy male subjects and female subjects of nonchildbearing potential between 18 and 55 years old.
2. Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lb).
3. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
4. Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests and other study procedures.

Exclusion Criteria

1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
2. Any condition possibly affecting drug absorption (eg, gastrectomy).
3. A positive urine drug test.
4. Subjects who currently smoke.
5. History of regular alcohol consumption exceeding 7 drinks/week for female subjects or 14 drinks/week for male subjects (1 drink = 5 ounces \[150 mL\] of wine or 12 ounces \[360 mL\] of beer or 1.5 ounces \[45 mL\] of hard liquor) within 6 months before screening.
6. Subjects with history of known sensitivity to esomeprazole or substituted benzimidazoles.
7. Treatment with an investigational drug within 30 days or 5 half-lives preceding the first dose of study drug.
8. Screening supine BP greater than or equal to 140 mm Hg (systolic) or greater than or equal to 90 mm Hg (diastolic), following at least 5 minutes of supine rest.
9. Screening supine 12-lead triplicate ECG demonstrating a corrected time from the beginning of the Q wave to the end of the T wave corresponding to electrical systole (QTc) interval \>450 msec or a QRS complex \>120 msec.
10. Subjects with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study-specific laboratory and confirmed by a single repeat test, if deemed necessary:

1. Aspartate aminotransferase (AST) or ALT level greater than or equal to 1.5 × upper limit of normal (ULN);
2. Total bilirubin (TBili) level greater than or equal to 1.5 × ULN; subjects with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is less than or equal to ULN.
11. Male subjects who are unwilling or unable to use 2 highly effective methods of contraception as outlined in this protocol for the duration of the study and for at least 90 days after the last dose of investigational product.
12. Use of prescription or nonprescription drugs and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of IP.
13. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.
14. History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen (HepBsAg), hepatitis B core antibody (HepBcAb), or hepatitis C antibody (HCVAb).
15. Unwilling or unable to comply with the criteria in the Lifestyle Requirements section of this protocol.
16. Subjects who are investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees, including their family members, directly involved in the conduct of the study.
17. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or crizotinib cMS and/or esomeprazole administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Pfizer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

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Pfizer New Haven Clinical Research Unit

New Haven, Connecticut, United States

Site Status

Countries

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United States

Other Identifiers

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PPI/FE

Identifier Type: OTHER

Identifier Source: secondary_id

A8081066

Identifier Type: -

Identifier Source: org_study_id