Evaluate Taste and Relative Bioavailability of Two Microsphere Formulations of Crizotinib in Healthy Participants

NCT ID: NCT03978143

Last Updated: 2019-11-15

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

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

25 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-06-12

Study Completion Date

2019-10-17

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The primary purpose of the study is to estimate the relative bioavailability and palatability of 2 new crizotinib formulations to the commercially available crizotinib formulated capsule at a 250 mg dose administered under fasted conditions in adult healthy participants. Additionally, this study aims to assess the safety and tolerability of crizotinib 250 mg single dose in 4 formulations when given fasted, with high fat meal, or with a proton pump inhibitor in healthy participants. Finally, this study will explore the effect of food or proton pump inhibitor on the pharmacokinetics of the 2 new crizotinib formulations.

We hypothesize 1 of the 2 new crizotinib formulations will have improved relative bioavailability and palatability than the formulated capsule under fasted or fed conditions with or without a proton pump inhibitor.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Healthy Volunteers

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Sequence 1

Receive treatments in the following order from Periods 1-6: A, B, C, D, E, G

Group Type OTHER

Treatment A

Intervention Type DRUG

Single 250 mg crizotinib dose as coated microsphere 1 (cMS1) formulation will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.

Treatment B

Intervention Type DRUG

A single 250 mg crizotinib dose as coated microsphere 2 (cMS2) formulation will be administered on the morning of Day 1 after overnight fast of at least 10 hours.

Treatment C

Intervention Type DRUG

A single 250 mg crizotinib dose as FC formulation will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.

Treatment D

Intervention Type DRUG

A single 250 mg crizotinib dose as OS will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.

Treatment E

Intervention Type DRUG

250 mg crizotinib as cMS1 formulation will be administered with high-fat, high-calorie meal after an overnight fast of at least 10 hours.

Treatment G

Intervention Type DRUG

40 mg esomeprazole will be administered

1 hour prior to dinner on Day -5 through Day -1. A single 250 mg crizotinib dose as cMS1 formulation will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.

Sequence 2

Receive treatments in the following order from Periods 1-6: A, C, B, D, E, G

Group Type OTHER

Treatment A

Intervention Type DRUG

Single 250 mg crizotinib dose as coated microsphere 1 (cMS1) formulation will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.

Treatment B

Intervention Type DRUG

A single 250 mg crizotinib dose as coated microsphere 2 (cMS2) formulation will be administered on the morning of Day 1 after overnight fast of at least 10 hours.

Treatment C

Intervention Type DRUG

A single 250 mg crizotinib dose as FC formulation will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.

Treatment D

Intervention Type DRUG

A single 250 mg crizotinib dose as OS will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.

Treatment E

Intervention Type DRUG

250 mg crizotinib as cMS1 formulation will be administered with high-fat, high-calorie meal after an overnight fast of at least 10 hours.

Treatment G

Intervention Type DRUG

40 mg esomeprazole will be administered

1 hour prior to dinner on Day -5 through Day -1. A single 250 mg crizotinib dose as cMS1 formulation will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.

Sequence 3

Receive treatments in the following order from Periods 1-6: B, A, C, D, E, G

Group Type OTHER

Treatment A

Intervention Type DRUG

Single 250 mg crizotinib dose as coated microsphere 1 (cMS1) formulation will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.

Treatment B

Intervention Type DRUG

A single 250 mg crizotinib dose as coated microsphere 2 (cMS2) formulation will be administered on the morning of Day 1 after overnight fast of at least 10 hours.

Treatment C

Intervention Type DRUG

A single 250 mg crizotinib dose as FC formulation will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.

Treatment D

Intervention Type DRUG

A single 250 mg crizotinib dose as OS will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.

Treatment E

Intervention Type DRUG

250 mg crizotinib as cMS1 formulation will be administered with high-fat, high-calorie meal after an overnight fast of at least 10 hours.

Treatment G

Intervention Type DRUG

40 mg esomeprazole will be administered

1 hour prior to dinner on Day -5 through Day -1. A single 250 mg crizotinib dose as cMS1 formulation will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.

Sequence 4

Receive treatments in the following order from Periods 1-6: B, C, A, D, F, H

Group Type OTHER

Treatment A

Intervention Type DRUG

Single 250 mg crizotinib dose as coated microsphere 1 (cMS1) formulation will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.

Treatment B

Intervention Type DRUG

A single 250 mg crizotinib dose as coated microsphere 2 (cMS2) formulation will be administered on the morning of Day 1 after overnight fast of at least 10 hours.

Treatment C

Intervention Type DRUG

A single 250 mg crizotinib dose as FC formulation will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.

Treatment D

Intervention Type DRUG

A single 250 mg crizotinib dose as OS will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.

Treatment F

Intervention Type DRUG

250 mg crizotinib as cMS2 will be administered with a high-fat, high-calorie meal after an overnight fast of at least 10 hours.

Treatment H

Intervention Type DRUG

40 mg esomeprazole will be administered

1 hour prior to dinner on Day -5 through Day -1. A single 250 mg crizotinib dose as cMS2 formulation will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.

Sequence 5

Receive treatments in the following order from Periods 1-6: C, A, B, D, F, H

Group Type OTHER

Treatment A

Intervention Type DRUG

Single 250 mg crizotinib dose as coated microsphere 1 (cMS1) formulation will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.

Treatment B

Intervention Type DRUG

A single 250 mg crizotinib dose as coated microsphere 2 (cMS2) formulation will be administered on the morning of Day 1 after overnight fast of at least 10 hours.

Treatment C

Intervention Type DRUG

A single 250 mg crizotinib dose as FC formulation will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.

Treatment D

Intervention Type DRUG

A single 250 mg crizotinib dose as OS will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.

Treatment F

Intervention Type DRUG

250 mg crizotinib as cMS2 will be administered with a high-fat, high-calorie meal after an overnight fast of at least 10 hours.

Treatment H

Intervention Type DRUG

40 mg esomeprazole will be administered

1 hour prior to dinner on Day -5 through Day -1. A single 250 mg crizotinib dose as cMS2 formulation will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.

Sequence 6

Receive treatments in the following order from Periods 1-6: C, B, A, D, F, H

Group Type OTHER

Treatment A

Intervention Type DRUG

Single 250 mg crizotinib dose as coated microsphere 1 (cMS1) formulation will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.

Treatment B

Intervention Type DRUG

A single 250 mg crizotinib dose as coated microsphere 2 (cMS2) formulation will be administered on the morning of Day 1 after overnight fast of at least 10 hours.

Treatment C

Intervention Type DRUG

A single 250 mg crizotinib dose as FC formulation will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.

Treatment D

Intervention Type DRUG

A single 250 mg crizotinib dose as OS will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.

Treatment F

Intervention Type DRUG

250 mg crizotinib as cMS2 will be administered with a high-fat, high-calorie meal after an overnight fast of at least 10 hours.

Treatment H

Intervention Type DRUG

40 mg esomeprazole will be administered

1 hour prior to dinner on Day -5 through Day -1. A single 250 mg crizotinib dose as cMS2 formulation will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Treatment A

Single 250 mg crizotinib dose as coated microsphere 1 (cMS1) formulation will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.

Intervention Type DRUG

Treatment B

A single 250 mg crizotinib dose as coated microsphere 2 (cMS2) formulation will be administered on the morning of Day 1 after overnight fast of at least 10 hours.

Intervention Type DRUG

Treatment C

A single 250 mg crizotinib dose as FC formulation will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.

Intervention Type DRUG

Treatment D

A single 250 mg crizotinib dose as OS will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.

Intervention Type DRUG

Treatment E

250 mg crizotinib as cMS1 formulation will be administered with high-fat, high-calorie meal after an overnight fast of at least 10 hours.

Intervention Type DRUG

Treatment F

250 mg crizotinib as cMS2 will be administered with a high-fat, high-calorie meal after an overnight fast of at least 10 hours.

Intervention Type DRUG

Treatment G

40 mg esomeprazole will be administered

1 hour prior to dinner on Day -5 through Day -1. A single 250 mg crizotinib dose as cMS1 formulation will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.

Intervention Type DRUG

Treatment H

40 mg esomeprazole will be administered

1 hour prior to dinner on Day -5 through Day -1. A single 250 mg crizotinib dose as cMS2 formulation will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Male and female participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, and laboratory tests.
* Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
* Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lb).
* Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the informed consent document (ICD) and in this protocol.

Exclusion Criteria

* 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).
* Any condition possibly affecting drug absorption (eg, gastrectomy, gastric or intestinal bypass surgery, cholecystectomy).
* Any condition possibly affecting the ability to taste (eg, dysgeusia, respiratory infection).
* History of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C antibody (HCVAb). Hepatitis B vaccination is allowed.
* Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory test abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
* 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 crizotinib.
* Participants with history of known sensitivity to esomeprazole or substituted benzimidazoles.
* Previous administration with an investigational product within 30 days or 5 half-lives preceding the first dose of crizotinib (whichever is longer).
* A positive urine drug test or cotinine test.
* Screening supine blood pressure (BP) ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of supine rest. If BP is ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility.
* Baseline 12-lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, QT interval corrected using the Fridericia's method \[QTcF\] \>450 msec, complete left bundle branch block \[LBBB\], signs of an acute or indeterminate-age myocardial infarction, ST-T interval changes suggestive of myocardial ischemia, second- or third-degree atrioventricular \[AV\] block, or serious bradyarrhythmias or tachyarrhythmias). If QTcF exceeds 450 msec, or the QRS complex exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTcF or QRS complex values should be used to determine the participant's eligibility. Computer-interpreted ECGs should be overread by a physician experienced in reading ECGs before excluding participants.
* Participants 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: Aspartate aminotransferase (AST) or ALT level ≥1.5 × upper limit of normal (ULN); Total bilirubin (TBili) level ≥1.5 × ULN; participants 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 ≤ ULN; Estimated glomerular filtration rate (eGFR) \<60 ml/min/1.73 m2 (See Appendix 10.2 for calculation method).
* Male participants who are unwilling or unable to comply with the contraception requirement listed in Section 10.4.1.
* History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening. Binge drinking is defined as a pattern of 5 (male) and 4 (female) or more alcoholic drinks in about 2 hours. As a general rule, alcohol intake should not exceed 14 units per week (1 unit = 8 ounces (240 mL) beer,

1 ounce (30 mL) of 40% spirit or 3 ounces (90 mL) of wine).
* Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.
* History of sensitivity to heparin or heparin-induced thrombocytopenia.
* Participants who currently smoke.
* Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol.
* 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 Pfizer employees, including their family members, directly involved in the conduct of the study.
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Pfizer

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Pfizer New Haven Clinical Research Unit

New Haven, Connecticut, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

Related Links

Access external resources that provide additional context or updates about the study.

https://pmiform.com/clinical-trial-info-request?StudyID=A8081069

To obtain contact information for a study center near you, click here.

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

A8081069

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Chrysin Bioavailability and Safety
NCT07066839 COMPLETED NA