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

October 27, 2017 updated by: Pfizer

A Phase 1, Open-label, Single Dose Study To Evaluate The Effects Of Food And The Proton Pump Inhibitor, Esomeprazole, On The Pharmacokinetics Of Crizotinib In A Coated Microsphere Formulation In Adult Healthy Volunteers

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
18

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06511
        • Pfizer New Haven Clinical Research Unit

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
ACTIVE_COMPARATOR: Treatment A
(reference) Crizotinib cMS 300 mg in fasted state
Drug: Crizotinib
Crizotinib in a coated microsphere formulation
EXPERIMENTAL: Treatment B
(test) Crizotinib cMS 300 mg in fed state
Drug: Crizotinib
Crizotinib in a coated microsphere formulation
EXPERIMENTAL: Treatment C
(test) 5 days of esomeprazole 40 mg followed by crizotinib cMS 300 mg in fasted state
Drug: Crizotinib
Crizotinib in a coated microsphere formulation
Drug: Esomeprazole
Proton pump inhibitor, esomeprazole
EXPERIMENTAL: Treatment D
(test) 5 days of esomeprazole 40 mg followed by crizotinib cMS 300 mg with apple sauce.
Drug: Crizotinib
Crizotinib in a coated microsphere formulation
Drug: Esomeprazole
Proton pump inhibitor, esomeprazole
EXPERIMENTAL: Treatment E
(test) 5 days of esomeprazole 40 mg followed by crizotinib cMS 300 mg with orange juice
Drug: Crizotinib
Crizotinib in a coated microsphere formulation
Drug: Esomeprazole
Proton pump inhibitor, esomeprazole

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Time Frame: Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf)
Time Frame: Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose
AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf).
Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose
Maximum Observed Plasma Concentration (Cmax)
Time Frame: Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose
Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time Frame: Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose
Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose
Time of last observed concentration (Tlast)
Time Frame: Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose
Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose
Plasma Decay Half-Life (t1/2)
Time Frame: Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose
Apparent Oral Clearance (CL/F)
Time Frame: Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose
Apparent Volume of Distribution (Vz/F)
Time Frame: Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose
Number of Participants With Clinical Laboratory Abnormalities
Time Frame: Baseline up to 35 calendar days after the last crizotinib dose
Baseline up to 35 calendar days after the last crizotinib dose
Number of Participants With Abnormal Electrocardiogram (ECG)
Time Frame: Baseline up to 35 calendar days after the last crizotinib dose
Baseline up to 35 calendar days after the last crizotinib dose
Number of Adverse Events by Severity
Time Frame: Baseline up to 35 calendar days after the last crizotnib dose
An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. AEs are classified according to the severity in 3 categories a) mild - AEs does not interfere with participant's usual function b) moderate - AEs interferes to some extent with participant's usual function c) severe - AEs interferes significantly with participant's usual function.
Baseline up to 35 calendar days after the last crizotnib dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 20, 2017

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 19, 2017

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 17, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 26, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 28, 2017

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 2, 2017

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 31, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 27, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • A8081066
  • PPI/FE (OTHER: Alias Study Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Information relating to our policy on data sharing and the process for requesting data can be found at the following link: http://www.pfizer.com/research/clinical_trials/trial_data_and_results/data_requests

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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